FACULTY OF
MEDICINE
2003 Research Report
Anaesthesia Anatomy Biochemistry Community, Occupational & Family
Medicine Diagnostic Radiology Medicine Microbiology Obstetrics &
Gynaecology Ophthalmology Orthopaedic Surgery Otolaryngology Paediatrics
Pathology Pharmacology Physiology Psychological Medicine Surgery
OUR VISION
THE NATIONAL UNIVERSIT Y OF SINGAPORE
has a clear vision to strive towards a global knowledge
enterprise – building synergies between, education, research
and entrepreneurship. In line with this vision, the Faculty of
Medicine endeavours to play a focal role in Singapore’s Life
Science’s Initiative and Singapore Medicine by encouraging
basic and translational research in the biomedical sciences
which will contribute towards improvement in national healthcare
and medical excellence.
Cover image compliments of Professor Ariff Bongso
RESEARCH HIGHLIGHTS
Faculty Of Medicine Research Report 2003
65
Orthopaedic Surgery
70
Otolaryngology
74
Paediatrics
83
Pathology
DEPARTMENTS
88
Pharmacology
13
Anaesthesia
94
Physiology
16
Anatomy
101 Psychological Medicine
22
Biochemistry
104 Surgery
28
Community,
Occupational
& Family Medicine
110 NUMI
35
Diagnostic Radiology
38
Medicine
45
Microbiology
50
Obstetrics
& Gynaecology
57
Ophthalmology
02
05
FOREWORD
PROGRAMMES
115 AWARDS & PRIZES
119 PATENTS
121 GRADUATE STUDENTS
FOREWORD
Faculty Of Medicine Research Report 2003
FOREWORD
The National University of Singapore has a clear vision to strive towards a
global knowledge enterprise – building synergies between education, research and entrepreneurship.
In line with this vision, the Faculty of Medicine is proud to play a focal role in Singapore’s Life
Science’s Initiative and Singapore Medicine by encouraging basic and translational research which
will contribute towards improvement in national healthcare and medical excellence.
This past year, one of the most significant events which the Faculty has had to contend with was
the Severe Acute Respiratory Syndrome (SARS), a newly emerged infectious disease that first
appeared in late 2002. As an integral part of the medical community, the Faculty of Medicine joined
the battle against SARS by focusing on the virology and immunology of SARS. The University
contributed its expertise in epidemiology and, together with the Singapore General Hospital, played
a key role in confirming the identity of the etiological agent. With an eye to long-term vigilance,
the Department of Medicine contributed a paper in Lancet (May 2003) reflecting the protean
presentations experienced in a non-SARS hospital.
The Faculty also wishes to highlight the achievements of the following Faculty members. Professor
Ariff Bongso’s research in embryonic stem cell biology offers promise for the treatment of a variety
of incurable disease through regenerative medicine. This earned him the Excellence for Singapore
Award 2003. The discovery of the gene RUNX3, a family of human cancer genes that could suppress
the growth of cancer cells in the stomach by Professor Yoshiaki Ito won him Japan’s most prestigious
recognition of cancer research, the Tomizo Yoshida Award 2003. Another noteworthy faculty
member’s achievement is that of Dr Allen Yeoh. His outstanding work in developing predictive
models to determine the optimal treatment of Acute Lymphoblastic Leukaemia (ALL) – the most
common form of childhood cancer won him the 2003 BMRC Young Investigator Award and the
Gold Asian Innovation Award 2003.
In terms of research output, the Faculty continues to win strong funding support from the National
Medical Research Council (NMRC) and the Biomedical Research Council (BMRC). The Faculty
attracted over $19.2 million in research funding in FY 2003/04. Moreover, the Faculty’s staff
significantly increased the proportion of publications in top tier journals.
In conclusion, the Faculty’s research drive continues with a key emphasis on multidisciplinary
programmes involving other research institutes and centres in Singapore and internationally.
Professor John Wong
Dean
Faculty of Medicine
Faculty of Medicine Research Report 2003
3
SOURCE OF FUNDING
AMOUNT (S$)
A*STAR
5,355,070
Ministry of Education
1,890,151
Ministry of Health
10,063,877
Ministry of Defence
73,750
Defence Science & Technology Agency (DSTA)
319,808
Other Organisations
1,588,353
Total
19,291,009
Breakdown of Grant Funding
Number of
Publications
400
Tier 2 & Above
350
300
255
250
199
195
202
200
(75.0%)
177
150
129
134
135
100
(39.3%)
(37.3%)
(39.9%)
1996
1997
1998
(50.6%)
(49.9%)
(62.9%)
(68.1%)
50
0
1999
2000
2001
2002
2003
Research Publications (International Referred)
4
Faculty of Medicine Research Report 2003
Year
PROGRAMMES
Faculty Of Medicine Research Report 2003
PROGRAMMES
GERONTOLOGY RESEARCH PROGRAMME
http://www.med.nus.edu.sg/research/progrsch/gerontology.shtml
Research Theme:
The Gerontology Research Programme (GRP) was formed to coordinate and facilitate multi-disciplinary research on a wide range of research
topics. A systematic and coordinated programme of research activities on the health of the elderly population in Singapore, it aims to help
understanding of the population aging transition and provide the scientific information needed for formulating strategies of disease prevention
and health promotion. Under the GRP, multi-disciplinary research groups from all sectors of the healthcare system, are establishing cohorts
of elderly subjects, both healthy and diseased, for gerontological research, at all levels of care: primary preventive, primary care, hospital,
community hospital and nursing homes.
A BMRC grant of $1.4 million was awarded for three years for the Singapore Longitudinal Aging Study (SLAS).
Ongoing Projects, Collaborations and Activities in 2003:
‘Singapore Longitudinal Aging Study’: SLAS is the principal population-
based longitudinal cohort study in the GRP. The GRP combines its
research mission with social service at its SLAS study centre in South
East Community Development Council by forging close community
relations with local grass-root leaders and residents, and providing
free health examination and talks. Papers have been published on
the prevalence of dementia, trends in elderly suicides, use of Chinese
herbal medicines, and others.
‘National Mental Health Survey of the Elderly 2003’. Collaborating
institutions: Institute of Mental Health, NUS Department of
Psychological Medicine. Researchers: Dr Chiam Peak Chiang, Assoc
Prof Ng Tze Pin, Prof Kua Ee Heok.
‘Hospital readmissions, mortality and quality of life of COPD patients
and their predictors’. Collaborating institutions: Ang Mo Kio Community
Hospital and St Luke’s Hospital for the Elderly. Researchers: Dr David
Yong, Dr Fong Ngan Phoon, Dr Sanjiv Kishore, Assoc Prof Ng Tze Pin.
‘Cognitive impairment, depression and functional outcomes of stroke
patients in community hospital care’. Collaborating institutions:
Singapore General Hospital and Tan Tock Seng General Hospital.
Researchers: Assoc Prof Philip Eng, Dr Ong Kian Chung, Dr Cao
Zhenying, Assoc Prof Ng Tze Pin.
‘Exercise and Cognitive Enhancement: Randomized Controlled Trial’.
Collaborators: Dr Steven Graham (Department of Social Work and
Psychology), Dr Tomasina Oh (English Language and Literature),
Assoc Prof Ng Tze Pin.
‘Community-based Early Psychiatric Interventional Strategy (CEPIS)’.
Collaborating institutions: Singapore Action Group of Elders
Counselling Centre, Ministry of Community Development and Sports
Elderly Division, NUS Department of Psychological Medicine.
‘Longitudinal Study of Cognitively Normal Elders Relating Brain
Structure, Function and Cognition to Factors Known to Modulate
Cognition in the Elderly’. Collborating institutions: Cognitive
Neuroscience Laboratory, Department of Endocrinology, Singapore
General Hospital, SGH Brain Centre. Researchers: Assoc Prof Michael
Chee, Dr Tai E Shyong, Dr Donald Yeo.
‘Singapore-Sweden Collaborative Study of Cultural Differences in
Aging’ Alzheimer's Disease Research Centre, Dept of Clinical
Neuroscience and Elderly Care Research, Karolinska Institute: a intercountry comparative study of ethnic and cultural differences in aging.
Assoc Prof Ng Tze Pin was invited to be a member of the Editorial
Board of ‘Brain Aging - An International Journal’.
HELICOBACTER PYLORI
http://www.med.nus.edu.sg/research/progrsch/helicobacter_pylori.shtml
Research Theme:
To identify molecular mechanisms of pathogenesis of Helicobacter pylori and improve treatment.
Specific themes
1. Molecular mechanisms of pathogenesis of H. pylori: why do only a minority of hosts develop disease.
2. Role of H. pylori in gastric cancer.
3. Epidemiologic studies on H. pylori and gastrointestinal diseases.
4. Diagnostics and therapeutics.
6
Faculty of Medicine Research Report 2003
Programme Activities:
Research studies were undertaken to investigate the role of
Helicobacter pylori in gastrooesophageal reflux disease.
Investigators from the Departments of Medicine, Pathology and
Microbiology collaborated to study the prevalence of H pylori infection,
its topographic distribution, the presence of single or multiple strains
of H pylori and genotypes as well as the pattern of associated gastritis
in patients with GERD compared with those without this condition.
The study found that the frequency and topographic distribution of
H pylori were similar in patients with GERD and those in the control
group with functional dyspepsia. H pylori colonisation of the cardia
was less common in reflux patients than in ulcer patients. These
results suggested that H pylori was unlikely to be aetiologically
involved in GERD.
LACTIC ACID BACTERIAL (LAB) INTEREST GROUP
http://www.med.nus.edu.sg/research/progrsch/lab.shtml
Research Theme:
Intestinal lactic acid bacteria as probiotics and vectors for gene therapy.
Programme Activities:
T he programme was initiated in August 1998. Members of the
programme have secured the following research grants.
1. Assoc Prof Bay BH (PI), Dr R Mahendran, Assoc Prof Lee YK.
Effect of lactic acid bacteria in the tumorigenesis of bladder and
breast cancer. Supported by NMRC.
2. Dr Lim CK (PI), Assoc Prof Lee Yuan Kun. Cloning of human genes
into lactobacilli. Supported by SRS.
3. Assoc Prof Lee YK (PI), Assoc Prof Tan HM. Lactic acid bacteria
as animal probiotics. Supported by Kemin Industies (A) Pte Ltd.
4. Assoc Prof Lee YK (PI), Dr Lu JH. Host-bacteria and bacteria
-bacteria interactions in human gastrointestinal tract. Supported
by NMRC.
5. Assoc Prof Lee YK (PI), Prof J Kwang, Assoc Prof Ng ML,
Dr Lim CK. Gene expression and colonization of lactic acid
bacteria in gastrointestinal tract. Supported by NMRC.
6. Assoc Prof Lee YK (PI), Assoc Prof Bay Boon Huat, Dr R Mahendran.
Modulation of the development and progression of cancer by
lactobacilli. Supported by NMRC.
The LAB Interest Group is in collaboration with the following
research groups:
1. Asthma and Allergy Research Programme, NUS Development of
prophylatic and therapeutic vaccines for asthma and allergy.
2. Immune response to allergens in early childhood in relation to
environmental factors.
3. Medical Nutrition Group, Karolinska Institute, Sweden Host
microbe cross-talk focuses on colon cancer.
4. Functional Food Center, Turku University, Finland Bacterial
adhesion and gene expression in human colonocytes: target for
probiotic development.
Publications:
1. Salminen S, Playne M, Lee YK (2003) Successful Lactobacilli: Human Studies on Probiotic efficiency. In: Handbook of Functional Dairy
Products. Ed. Shortt C, O Brien. CRC Press, Boca Raton, Fl. Pp. 13-32.
2. Lee YK, Puong KY, Ouwehand AC, Salminen S (2003) Displacement of bacteria pathogens from mucus and Caco-2 cell surface by
lactobacilli. Journal of Medical Microbiology 52: 925-930.
LIVER RESEARCH GROUP
http://www.med.nus.edu.sg/research/progrsch/hepliver_work_grp.shtml
Research Theme:
Investigate liver development, physiology and liver disease.
Faculty of Medicine Research Report 2003
7
Programme Activities:
The Division of Gastroenterology played a major role as “anchor
tenant” of the group providing guidance, coordination and resources
to ensure individual members were able to constructively pursue
their research activities. The group has expanded and two major
themes have emerged as focus of research activity. The first is liver
cell differentiation and function, and the second is liver disease
complications especially hepatocellular carcinoma and cirrhosis.
Members of the group are taking a variety of approaches to these
subjects and followup meetings will enable cross fertilization of ideas
and consolidation of research strategy. Such approaches include cell
culture approaches, proteomics, microarray, animal models and
molecular biology techniques. Additional members of the group now
include Cao Tong and Alexis Heng from Dentistry, Chen Chien-Shing
from Oncology-Haematology, Dennis Wang from Surgery, Evelyn Koay
and Zhang Daohai from Molecular Diagnostics, Wang Naidy and Shen
Shali from Physiology and Robert Hewitt from Pathology/Tissue
Repository. We look forward to a fruitful and productive collaboration.
NEURODEGENERATION
http://www.med.nus.edu.sg/research/progrsch/neurodegeneration.shtml
Research Theme:
To study factors which contribute to, or modulate, degeneration of the nervous system. Research is centered on the calcium hypothesis of
aging and dementia, and examines factors that contribute to, or modulate calcium influx into neurons. The role of calcium dependent and
free radicals in events leading to neurodegeneration, and the role of glial cells in propagating neuronal injury are also examined. In addition
to calcium, an accumulation of iron and cholesterol oxidation products can also be toxic to neurons, and research is carried out, to elucidate
iron and cholesterol metabolism in the brain.
Programme Activities:
Collaborative projects have been carried out between members of
the group, resulting in several papers in premium journals, book
chapters, and awards at international conferences. Individual members
have also been awarded several grants for research on cell models
of neurodegenerative diseases, and translational research, on the
development of antioxidants to treat neurological disorders.
NEUROPSYCHOPHARMACOLOGY
http://www.med.nus.edu.sg/research/progrsch/neuropsychopharmacology.shtml
Research Theme:
The pharmacology of drugs that may exert neural, psychological and behavioural changes in animals and human.
Programme Activities:
1. Department of Pharmacology has Noldus EthoVision Pro Version
2.3, a behavioural video tracking system and water maze, radialarm mazes, and elevated-plus mazes for assessment of cognitive
function and anxiety in both rats and mice.
2. Department of Neurology, NUS has a clinical phase 1/2 trial on
a new drug in acute ischemic stroke.
3. Local Meetings: There were formal and informal meetings with
various programme members to discuss collaborations and
grant application.
4. Regional collaboration: Prof Kua and Assoc Prof Tan are involved
in International Study on Psychotropic Drug Prescription in
psychiatric patients.
5 . International meetings: President of CINP (Collegiums
International Neuropsychopharmacologicum) is planning to set
up a regional committee for CINP. Assoc Prof Tan was invited
to participate.
6. Hosting of Neurospsychiatrists from Japan.
Students passed PhD candidature qualifying exams under the supervision of the Faculty of Neuropsychopharmacology
Programme:
Vivek Verma
“Comparison of the effects of typical and atypical antipsychotics on the locus coeruleus and prefrontal cortex”
Lim Ee Peng, Alice
“Investigating the Cognitive Effects of Atypical Antipsychotics - The Noradrenergic Hypothesis”
Tessi Sherrin
”Role of Cholecystokinin-B and Corticotropin Releasing Hormone Receptor in anxiety, depression and suicide”
8
Faculty of Medicine Research Report 2003
NITRIC OXIDE STUDY GROUP
http://www.med.nus.edu.sg/research/progrsch/nitric_oxide.shtml
Research Theme:
Nitric Oxide
Programme Activities:
Nitric Oxide (NO) is a free radical messenger with a half-life of only
a few seconds. It is synthesized as a bi-product by the biosynthetic
enzyme nitric oxide synthase (NOS) from its precursor arginine.
Nitric Oxide has been implicated to play an important role in the
control of eye movements in awake feline. The superior colliculus
exhibits dense immuno-label for NOS, which is co-localized with
other neurotransmitters, including acetylcholine and glutamate. Using
an amperometric method, the functional properties of NO released
from neurons can be measured in living rat superior colliculus slices.
We found that NO is released from neurons in the superior colliculus
in the presence of arginine. We also found that the release of NO
can be triggered by the application of glutamate or acetylcholine in
the same region of the slice. The responses varied from single
to multiple releases, which could last for up to hundreds of seconds.
The multiple releases could have been produced by a local feedback
system and/or by an intrinsic trap-release mechanism of NO
by s-nitrosothiols. Previous studies have demonstrated that glutamate
is associated with the local excitatory circuitry in the superior colliculus
that commands saccades and that the visual input to this circuitry
can be enhanced by acetylcholine. The present experiments extend
these findings by providing evidence that NO may contribute
to the initiation of saccades by modulating these excitatory
glutamatergic and cholinergic circuits in the superior colliculus. (Sheu
Fwu-Shan’ group)
PROGRAMME IN ENVIRONMENTAL MICROBIOLOGY
http://www.med.nus.edu.sg/research/progrsch/environmental.shtml
Research Theme:
Genomics and proteomics of environmental microorganisms, detection of environmental bacteria and viruses by flow cytometry and
molecular approaches.
Programme Activities:
New Grant Funding obtained:
Collaboration amongst members on development of flow cytometry
for differentation of viable and non-viable bacteria, isolation of
enzymes with better catalytic properties for the degradation of
aromatic hydrocarbons, determination of genes influenzing biofilm
formation in Pseudomonas aeruginosa.
Proteome mapping of aromatic hydrocarbon -induced response in
Pseudomonas alcaligenes P25X.
Patents:
1. Yeo CC, Wong MV, Feng Y, Song KP, Poh CL. Molecular characterization of an inducible gentisate 1,2- dioxygenase gene, xInE, from
Pseudomonas alcaligenes NCIMB 9867. Gene. 2003 Jul 17;312:239-48.
2. Teo JW, Zhang LH, Poh CL. Cloning and characterization of a novel lipase from Vibrio harveyi strain AP6. Gene. 2003 Jul 17;312:181-8.
3. Teo JW, Zhang LH, Poh CL. Cloning and characterization of a metalloprotease from Vibrio harveyi strain AP6. Gene. 2003 Jan
16;303:147-56.
PROGRAMME IN INFECTIOUS DISEASES (PID)
http://www.med.nus.edu.sg/research/progrsch/infectious.shtml
Research Theme:
Molecular strategies for the diagnosis, epidemiology and prevention of infectious diseases.
Faculty of Medicine Research Report 2003
9
Programme Activities:
By RT-PCR using universal enterovirus primers, and by a newly
developed semi-nested assay using EV71-specific primers, the
predominant causative agent of the hand, foot and mouth disease
(HFMD) outbreak in Singapore in 2000 was identified to be enterovirus
type 71 (EV71). The complete viral genomes of a virulent and a nonvirulent EV71 strain isolated from the HFMD outbreak were sequenced,
and a structural model of EV71 predicted. A study on the “infectomics”
of EV71 infection of rhabdomyosarcoma cells by differential display
RT-PCR has been successfully concluded. Mapping of EV71 epitopes
and development of specific EV71 monoclonal antibodies are in
progress. Suitable EV71 structural gene targets have been successfully
cloned into DNA vaccine constructs, while animal immunization,
challenge and protection studies (in collaboration with Johns Hopkins
Singapore) are approaching completion. To develop DNA vaccines
against dengue, DNA constructs containing structural and nonstructural genes of dengue viruses have been cloned, and shown to
be expressed in eukaryotic cells. Interactions between dengue viral
and host cellular proteins are being investigated. Methods to improve
the yield of DNA vaccine plasmids are being analyzed in collaboration
with the Bioprocessing Technology Centre. Host immune responses
to dengue infections and flaviviral vaccines have been evaluated
using several immunological assays.
In conjunction with the Ministry of Health and the NUS Department
of Community, Occupational and Family Medicine, a national
seroepidemiological survey of Chlamydia pneumoniae infections in
a large cohort comprising more than 1,000 subjects in Singapore has
been published. This survey revealed a high prevalence of IgG
antibodies in the Singapore population especially in males and in
older age groups. Several immunological assays are being evaluated
and compared for the detection of antibodies to Chlamydia
pneumoniae.
Other ongoing projects include sequencing of the elongation factor
Tu gene and a novel gene from Bartonella henselae; toxigenesis in
Clostridium difficile; periodontal disease; and immunopathogenesis
of Mycobacterium tuberculosis.
TISSUE ENGINEERING
http://www.med.nus.edu.sg/research/progrsch/tissue_engine.shtml
Research Theme:
Musculoskeletal tissue regeneration and repairs.
Programme Activities:
1 ) Isolation, Culture and Characterization of Mesenchymal
Stem Cells (PI: Prof EH Lee)
Mesenchymal stem cells (MSCs) have been isolated, cultured
and used to repair defects of the musculoskeletal system, including
bone, cartilage and tendon/ligament. Several experiments have
been conducted to demonstrate the ability of MSCs to regenerate
these tissues in animals. We are currently collaborating with
researchers from research institutions including IMCB and GIS
in the characterization of these stem cells.
2) Functional Tissue Mechanics (PI: Assoc Prof James Goh)
We have set up a facility for the objective evaluation of
regenerated and repaired tissues and more importantly for invitro engineered tissues. This is an important aspect, which is
often neglected, in tissue engineering research. Regenerated or
engineered tissues are required to function in-situ and are usually
subjected to certain in-service load. Therefore it is vital that the
new tissue has similar mechanical properties as the normal
tissues and is able to withstand the in-service loads. Specialised
testing apparatus are required to conduct these tests. Furthermore,
in conjunction with the NUS Division of Bioengineering, theoretical
models using computational bioengineering techniques to
predict loading stresses have been developed.
10
3) Clinical Trial on Autologous Chondrocyte Transplantation
(PI: Prof EH Lee)
Following promising outcomes from previous clinical trials, a
Therapeutic Tissue Engineering Lab (including a Class 10K
Cleanroom) has been set up by the department in NUH.
Chondrocytes have been successfully expanded in-vitro and used
to treat cartilage defects in the knee. The procedure for the
procurement of biopsy has been established and practiced, and
the cells isolated from these have shown great proliferating
ability. Millions of viable cells can be harvested from cell culture
for autologous cell implantation. To date, more than 70 patients
have been treated using this technique in Singapore. More than
86% of our patients showed significant improvement in the SF
36, ICRS Cartilage Injury Evaluation Package 2000 and IKDC
Knee Examination form 2000 evaluation.
4) Osteochodral Repair / Regeneration (PI: Prof EH Lee)
The NUS Dept of Orthopaedic Surgery and the Division of
Bioengineering worked together to develop a bioresorbable
scaffold specifically designed for articular bone/cartilage tissue
substitutes. The objective of this project to develop a cell culture
system that allows the tissue engineering of cartilage attachedto
subchondral bone. They also attempted to evaluate the
biologicaland biomechanical properties of the engineered articular
bone/cartilage interphase tissue in an animal model.
Faculty of Medicine Research Report 2003
5) Ligament (PI: Assoc Prof James Goh)
The NUS Dept of Orthopaedic Surgery and Division of
Bioengineering are collaborating to develop a tissue-engineered
ligament. Mesenchymal stem cells are harvested and expanded
and are seeded directly onto a scaffold made of bioabsorbable
material such as a combination of polylatic acid and poly
(-caprolactone). The whole construct is then incubated to further
expand the number of cells. An important consideration in tissue
engineered ligament is to induce fibroblast formation with the
cell aligned longitudinally. In addition, the group is designing
and developing an apparatus to provide cyclic tensile stimulus
to enhance orientation of the cells and collagen fibers for
engineering ligaments.
6) Tendon (PI: Assoc Prof James Goh)
We have conducted a rabbit experiment to evaluate the effect
of marrow stromal cell-seeded knitted PLGA scaffold for Achilles
tendon repair. At 12 weeks post-operation, Results showed that
MSCs/knitted PLGA scaffold induced tendon-like tissue formation.
Tissues showed organized bundles of highly crimped fibers. The
volume of PLGA scaffold has reduced and synovial cells were
observed along the surface of the neo-tenodons. The results
indicated that marrow stromal cell-seeding knitting PLGA fiber
scaffold is promising for tendon regeneration.
7) Spine (PI: Assoc Prof HK Wong)
The NUS Dept of Orthopaedic Surgery and the Division of
Bioengineering are collaborating to design and develop the spinal
implant for fusion based on a bioabsorbable material. This implant
will be sufficiently strong to support the requisite loads. Using
tissue engineering techniques either osteoblasts or mesenchymal
stem cells are seeded into the 3D scaffold of the bioabsorable
material. With the introduction bone growth factor, e.g. bone
morphogenic protein (BMP), bone formation and fusion will be
enhanced. In the future, with the success of the tissue-engineered
osteochondral complex, a biological disc replacement may
be possible.
8) Muscle (PI: Dr James Hui)
Isolation and culture of Muscle-derived stem cells from rabbit
are being carried out and applied in experiments such as limb
lengthening in rabbits. Some preliminary results were obtained.
VENOM AND TOXIN RESEARCH PROGRAMME
http://www.med.nus.edu.sg/research/progrsch/venom_toxin.shtml
Research Theme:
From Venoms to Drugs, From Toxins to Therapeutics.
Programme Activities:
Purification, biochemical and pharmacological characterization as
well as molecular aspects of research involving cloning, sequencing
and expression of new toxins are actively being done by the academic
staff with the help of research fellows, research assistants and
postgraduate students. A range of novel toxins from different species
of scorpions, spiders and cone shells have been isolated, purified,
sequenced and the synthetic toxins being screened for novel biological
activities. Several channel toxins, specific for sodium, potassium or
calcium channels, have been extensively studied with respect to their
structure, mode of action, and localization of the functional site. On
detection of toxins, the working prototype on ISFET has been
established, miniaturized and packaged. Solid phase Micro Extraction
(SPME) techniques are also being established and used to detect
marine toxins in collaboration with the Defence Science Organization.
Crystallographic studies are in progress on stonus toxin and
phospholipase A2 toxins from an Australian Elapid. A novel antitoxic
and anti-inflammatory protein has been discovered from a nonvenomous snake serum, which forms the basis for cloning studies,
leading to production of a recombinant protein that is proven useful
as a therapeutic agent for snake envenomation and inflammatory
diseases. Further studies are in progress to develop this protein with
therapeutic potential into a potent anti-inflammatory drug or as an
investigative tool for structure-function studies. Many interesting
peptides have been characterized from conus venom.
Patents:
Gopalakrishnakone P, Thwin MM, Ong WY, Sato K. (2003) Phospholipase A2-inhibitory peptide with anti-arthritic and neuroprotective activities.
US Provisional Application No. 60/466,421 /INTRO Ref: GOPAL P 08-US/PRV. Filing Date: 30 April 2003.
Faculty of Medicine Research Report 2003
11
Anaesthesia
13
Anatomy
16
Biochemistry
22
Community, Occupational
& Family Medicine
28
Diagnostic Radiology
35
Medicine
38
Microbiology
45
Obstetrics &
Gynaecology
50
Ophthalmology
57
Orthopaedic Surgery
65
Otolaryngology
70
Paediatrics
74
Pathology
83
Pharmacology
88
Physiology
94
Psychological Medicine
101
Surgery
104
National University
Medical Institutes
110
DEPARTMENTS
Faculty Of Medicine Research Report 2003
DEPARTMENT OF
Anaesthesia
THE DEPARTMENT’S RESEARCH FOCUS IS ON
THE FOLLOWING:
a)
PAIN RESEARCH
Professor Lee Tat Leang and team will be focusing on pain research, both of
acute and chronic pain in both animal models and in humans. The mechanisms
of pain, the peptides involved, the processing pathway are being studied, with
the view of developing agents that would interrupt this pathway.
b)
CARDIOTHORACIC OUTCOME DATABASE
The present database started in January 2003, and is expected to reach critical
mass in late 2004. The database is done in collaboration with the Cardiothoracic
Department. Of interest is the neurological outcome, which is an area of intense
interest in the literature. The database will generate research ideas both in
basic and clinical studies to improve outcomes.
c)
CLINICAL RESEARCH
Clinical studies have been the mainstay of our research to date. These research
are in the areas of the airway, pharmacology of anaesthesia agents, sedation
as well as coagulation. Many of these studies are done in collaboration with
NUH clinical staff, on the 18,000 patients who are seen by the Department
each year.
Faculty of Medicine Research Report 2003
13
The immune response to cardiopulmonary bypass in
diabetic patients
Project Description
Principal Investigator
Co-Principal Investigator
Collaborators
Grants Awarded in 2003
The effect of different heparins and activators on activated
clotting time
Principal Investigator
Co-Principal Investigator
Collaborators
: Dr Dave Kang Song Chua (NUH)
: Dr Ti Lian Kah
: Dr Sophia Ang Bee Leng,
Ms Ng Bok Lan (NUH)
Principal Investigator
Co-Principal Investigators
: Dr Tan Chee Keat (NUH)
: Dr Eugene Liu,
Prof Lee Tat Leang
Principal Investigators
To evaluate the use of dexmedetomidine for conscious sedation
in dental surgery
The influence of neuromuscular blockade on the incidence of air
leakage and gastric insufflation from the laryngeal mask airway
during positive pressure ventilation
Principal Investigator
Co-Principal Investigator
Collaborator
: Dr Winston Tan Kwong Shen
: Dr Ti Lian Kah,
Prof Lee Tat Leang,
Assoc Prof Ho Kee Hai
Principal Investigator
Co-Principal Investigator
Collaborators
Women have a poorer outcome after cardiac surgery: A result of
size or gender?
: Dr Ti Lian Kah
: Dr Dave Kang Song Chua (NUH)
Investigation of the use of dexmedetomidine for conscious
sedation for cataract surgery
Principal Investigator
Collaborators
: Dr Pua Hwee Leng (NUH)
: Dr Ti Lian Kah
: Dr Vincent Yeo (NUH)
: Mary Ho (NUH)
: Dr Ti Lian Kah
: Dr Chiu Jen Wun (KKWCH),
Ms Karen Ho Ban Shian
Plasma levels and clinical efficacy of different doses of intraendotracheal cuff lignocaine
Principal Investigators
Principal Investigator
Collaborator
: Dr Sim Chin Keng (NUH),
Prof Lee Tat Leang
: Dr Xu Pei Chang (NUH)
The effect of cerebrospinal fluid on coagulation – Does it differ
for obstetric patients?
Ongoing Projects
Principal Investigator
Collaborators
The role of acupuncture in the treatment of neck pain
Collaborator
Intramuscular injection of Botulinum toxin A (Botox Allergen) for
the treatment of frozen shoulder
: Dr Constance Tham (NUH)
: Assoc Prof Cheong Keng Fatt
: Dr Helen Isaac,
Assoc Prof Shabbir Moochhala (DMRI)
: Dr Sophia Ang Bee Leng (NUH)
: Dr Ti Lian Kah,
Dr Eugene Liu,
Assoc Prof Paul Chew
Effect of erythromycin, metoclopramide or combination therapy
on gastric emptying in the critically ill neurosurgical patients
Principal Investigator
Co-Principal Investigator
: Dr Ng Huey Ping (NUH)
: Assoc Prof Chen Fun Gee
Factors affecting the biospectral index and isoflurane
concentrations during cardiopulmonary bypass
Principal Investigator
Monitoring locomotion effects of neuropeptides
: Dr Ng Huey Ping (NUH),
Assoc Prof Cheong Keng Fatt
: Dr Eugene Liu
Identifying neuropeptide receptors locations in chronic pain models
14
Faculty of Medicine Research Report 2003
P r o c e s s i n g p a t h wa y o f n o c i c e p t i n a n d n o c i s t a t i n
from prepronociceptin
Principal Investigator
Collaborators
: Dr Tessy Joseph
: Prof Lee Tat Leang,
Dr Shinro Tachibana
Characterization of clinically significant peptides present in human
cerebrospinal fluid (CSF)
Principal Investigator
Collaborators
: Dr Shinro Tachibana
: Prof Lee Tat Leang,
Dr Siau Chiang (NUH),
Dr Tessy Joseph,
Ms S Rama,
Assoc Prof Peter Wong
Hypothermia and traumatic brain injury
Principal Investigator
Collaborators
: Assoc Prof Cheong Keng Fatt
: Dr Chou Ning,
Assoc Prof Koh Kwong Fah,
Assoc Prof Shabbir Moochhala (DMRI)
Analysis of the levels of nocistatin and nociceptin, in animal
models of chronic pain
Principal Investigator
Collaborators
Cheong KF, Tham C
Anaesthetic management of a child with Hallermann-Streiff
Francois syndrome. Paediatr Anaesth. 2003;13(6):551-2.
Mackensen GB, Ti LK, Phillips-Bute BG, Mathew JP, Newman MF,
Grocott HP
Cerebral embolization during cardiac surgery: impact of aortic
atheroma burden. Br J Anaesth. 2003;91(5):656-61.
Teo A, Koh KF
Coronary steal syndrome (Letter to Editor) Anaesthesia 2003;58:
95-6.
Ti LK, Cheong KF, Chen FG
The timing for the use of heparinase and thromboelastography
to prevent excessive bleeding after coronary artery bypass graft
surgery – Response. J Cardiothorac Vasc Anesth. 2003; 17:
414-5.
: Prof Lee Tat Leang
: Dr Shinro Tachibana,
Assoc Prof Peter Wong,
Assoc Prof Samuel Tay
Effect of acupuncture in cutaneous blood flow
Principal Investigator
Collaborators
Cheong KF, Tham SL
Anaesthetic management of a child with Hallermann-Streiff
Francois syndrome. Paediatr Anaesth. 2003;13(3):274-5.
: Prof Lee Tat Leang
: Dr Xu Pei Chang,
Dr Qiao Tian Ru
International Publications
Staff Profile
Associate Professor & Head
Professor
Associate Professor
Assistant Professors
:
:
:
:
Senior Research Fellow
Research Fellows
:
:
Research Assistant
:
Ti LK, Mackensen GB, Ti LK, Grocott HP, Laskowitz DT, Phillips-Bute BG,
Milano CA, Hilton AK, Newman MF, Mathew JP
Apolipoprotein E4 increases aortic atherom a burden in cardiac
surgical patients. J Thoracic Cardiovascular Surgery 2003;125(1):
211-3.
Contact Information
Contact Person
Telephone
:
:
Facsimile
E-mail
Postal Address
:
:
:
Homepage
:
Microdialysis of neuropeptides
Faculty of Medicine Research Report 2003
Chen Fun Gee
Lee Tat Leang
Cheong Keng Fatt
Ti Lian Kah
Eugene Liu Hern Choon
Shinro Tachibana
Tessy Joseph
Kazi Ahsan Jamil
Lee Chun Mei
15
Dr Ti Lian Kah
6772-4207
6772 4208
6777-5702
anatilk@nus.edu.sg
Department of
Anaesthesia
National University Hospital
5 Lower Kent Ridge Road
Singapore 119074
http://www.med.nus.edu.sg/
anaeweb
DEPARTMENT OF
Anatomy
THE DEPARTMENT HAS FOCUSED ON 3 MAJOR AREAS
OF RESEARCH :
Neuroscience
Venoms and Toxins
Cancer Cell Biology
To enhance the research environment in the Department, existing
laboratories have been upgraded and new laboratories have been set
up. In striving to improve the quality of research, the academic staff in
the Department has adopted a multidisciplinary approach by collaborating
with researchers from other NUS departments, and local and foreign
institutions. There is also active research collaboration with
scientists/clinicians of local hospitals. In order to promote the
entrepreneurial spirit, efforts have also been made to explore the
possibility of acquiring patents that have biomedical applications.
Staff members of the Department have been very active in research and
participate in multidisciplinary and programmatic research. The research
output from the Department has been remarkable and a good number
of the research findings have been published in excellent journals such
as “Cell”, an achievement that bears testimony to the potential and
research capabilities of the staff members.
The academic staff have published more than 50 papers in international
journals and 3 patents have been filed.
Total amount of research funds received by the Department for the year
2003 is $838,608.
16
Faculty of Medicine Research Report 2003
Global gene expression analysis of the human genome following
exposure to sarin
Project Description
Principal Investigator
Grants Awarded in 2003
The expression of IL-6 in the nerve fibers in the myocardium in
response to biomechanical stimuli might be a novel target to
treat heart failure
Principal Investigator
Collaborator
: Assoc Prof Samuel Tay Sam Wah
: Dr He Beiping
New therapeutics for PLA2-related disorders : a PLA2-inhibitory
peptide as potential candidate drug for modulation of rheumatoid
arthritis (a pilot study)
Principal Investigator
Collaborator
Principal Investigator
Collaborators
Ongoing Projects
Development of non-pathogenic lactobacillus as a potential vector
: Prof P Gopalakrishnakone
A. Evaluation of the Haffkine Polyvalent Antivenom against Naja
sumatrana (Black Spitting Cobra) venom
B. Naja sumatrana venom effects on rabbit cornea
Principal Investigator
Collaborators
: Prof P Gopalakrishnakone
: Dr Gregory Chan WM (TTSH),
Dr Ng Yee Kong,
Mr Arul Earnest (TTSH),
Mr Francis Lim (Singapore Zoological
Gardens),
Assoc Prof Shabbir Moochhala (DMRI)
Role of the choroid plexus in the development of brain white
matter damage (periventricular leukomalacia) following hypoxic
injury in the neonatal brain
Principal Investigator
Collaborator
: Dr George Yip Wai Cheong
: Assoc Prof Bay Boon Huat,
Dr Tan Puay Hoon (SGH)
: Prof Sit Kwok Hung
Development of bactericidal peptides against Burkholderia
pseudomallei
Principal Investigator
: Prof P Gopalakrishnakone
: Dr Maung Maung Thwin
Characterisation of the biological roles of different heparin
sulphate species in breast cancer development and metastasis
Directing difluorocytidine to the commitment point to kill
cancer cells
Principal Investigator
: Prof P Gopalakrishnakone
Principal Investigator
Collaborators
Evaluation of metallothionein as a molecular and prognostic
biomarker of breast cancer
Principal Investigator
Collaborators
: Assoc Prof Bay Boon Huat
: Assoc Prof Vincent Chow,
Dr Tan Puay Hoon (SGH)
Elucidation of functional metallalothionein mRNA isoforms in
breast myoepithelial, premalignant and malignant cells in vitro
Principal Investigator
Collaborator
: Assoc Prof Charanjit Kaur
: Dr Lu Jia (DMRI/DSTA)
Tissue Culture Lab
Faculty of Medicine Research Report 2003
: Assoc Prof Bay Boon Huat
: Assoc Prof Lee Yuan Kun,
Dr Ratha Mahendran,
Dr ST Dheen
17
: Assoc Prof Bay Boon Huat
: Assoc Prof Vincent Chow
Molecular bases for gestational diabetes-induced changes in the
nervous and visual systems of developing mouse embryos
Analysis of T-Box genes and their roles in the development of
vertebrate embryos
Principal Investigator
Collaborator
Principal Investigator
Collaborators
: Assoc Prof Samuel Tay Sam Wah
: Dr ST Dheen
: Dr ST Dheen
: Assoc Prof V Korzh (IMCB),
Dr K Swaminathan (DBS/IMCB)
Indirect transplantation of mesenchymal stem cells into the
hypoglossal nuclei after unilateral nerve avulsion - Prototype
model for treating neurodegenerative diseases
Analysis of regulatory factors involved in neurotoxicity in
neurodegenerative diseases
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Assoc Prof Samuel Tay Sam Wah
: Dr ST Dheen,
Dr He Beiping,
Dr Ji Junfeng
Investigation of neuronal response and glial reaction in the central
nervous system and its target visceral organs with special reference
to urinary bladder
Neurotoxic effects of domoic acid in rats
Principal Investigator
Collaborator
: Assoc Prof Charanjit Kaur
: Mr C Ananth
Principal Investigator
Collaborator
Characterization of heparan sulphate in the regulation of
spinal neurulation
Principal Investigator
: Dr George Yip
: Dr He Beiping
Principal Investigator
Roles of microglia in the diabetic visual system with special
reference to the retina
Principal Investigator
Collaborators
: Dr Ng Yee Kong
: Prof Ling Eng Ang,
Dr Zeng Xiao Xia (IMCB)
: Prof P Gopalakrishnakone
Multidisciplinary approach to design of a potent anti-inflammatory
agent for therapeutic applications
Principal Investigator
Collaborators
: Dr Liang Feng Yi
: Prof P Gopalakrishnakone
: Assoc Prof Khoo Hoon Eng
Application of microarray technology to divulge the molecular
mechanisms of drug resistance in mycobacteria
Principal Investigator
Systematic in situ expression mapping of novel genes and
molecular, functional characteristics of area-/cell type-specific
genes in central nervous system
: Prof Ling Eng Ang
: Dr Ng Yee Kong
Defibrinating proteinase from animal venom
Principal Investigator
Collaborator
Stimulus specific microglial activation : a possible mechanism to
modulate perineuronal microenvironment
Principal Investigator
: Dr ST Dheen
: Prof Ling Eng Ang,
Assoc Prof Samuel Tay Sam Wah
: Prof P Gopalakrishnakone
: Dr Maung Maung Thwin,
Dr B Cheng
International Publications
Phan TT, Lim IJ, Sun L, Chan SY, Bay BH, Tan EK, Lee ST
Quercetin inhibits fibronectin production by keloid-derived
fibroblasts. Implication for the treatment of excessive scars. J
Dermatol Sci. 2003; 33 (3) : 192-4.
Cherian MG, Jayasurya A, Bay BH
Metallothioneins in human tumors and potential roles in
carcinogenesis. Mutat Res. 2003; 533(1-2) : 201-9. Review.
Tai SK, Tan OJ, Chow VT, Jin R, Jones JL, Tan PH, Jayasurya A, Bay BH
Differential expression of metallothionein 1 and 2 isoforms in
breast cancer lines with different invasive potential: identification
of a novel nonsilent metallothionein-1H mutant variant. Am J
Pathol. 2003; 63(5) : 2009-19.
Neuroscience Lab
18
Faculty of Medicine Research Report 2003
Du HY, Olivo M, Tan BK, Bay BH
Ananth C, Gopalakrishnakone P, Kaur C
Hypericin-mediated photodynamic therapy induces lipid
peroxidation and necrosis in nasopharyngeal cancer. Int J Oncol.
2003;23 (5) : 1401-5.
Induction of inducible nitric oxide synthase expression in activated
microglia following DA-induced neurotoxicity in the hippocampus.
Neuroscience Lett. 2003 ;338 (1) : 49-52.
Selvarajan S, Bay BH, Mamat SB, Choo A, Chuah KL, Sivaswaren CR, Tien
SL, Wong CY, Tan PH
Al-Saleh SS, Kaur C, Ling EA
Detection of HER2/neu gene amplification in archival paraffinembedded breast cancer tissues by fluorescence in situ
hybridization. Histochem Cell Biol. 2003;120 (3) : 251-5.
Response of neurons and microglia/macrophages in the area
postrema following exposure to hypobaric hypoxia. Neuroscience
Lett. 2003; 346:77-80.
Lian Q, Tay SSW, ST Dheen
Phan TT, Sun L, Bay BH, Chan SY, Lee ST
Dietary compounds inhibit proliferation and contraction of keloid
and hypertrophic scar-derived fibroblasts in vitro: therapeutic
implication for excessive scarring. J Trauma. 2003;54 (6) : 121224.
Enhanced expression of transforming growth factor-beta
isoforms in the neural tube of embryos derived from diabetic
mice exposed to cyclophosphamide. Neuroscience Lett. 2003;351,
(1) : 51-5.
Van Dong L, Quyen le K, Eng KH, Gopalakrishnakone P
Huang J, Tan PH, Thiyagarajan J, Bay BH
Prognostic significance of glutathione S-transferase-pi in invasive
breast cancer. Mod Pathol. 2003;16 (6) : 558-65.
Jayasurya A, ST Dheen, Yap WM, Tan NG, Ng YK, Bay BH
Inducible nitric oxide synthase and bcl-2 expression in
nasopharyngeal cancer: correlation with outcome of patients
after radiotherapy. Int J Radiat Oncol Biol Phys. 2003 1;56(3):
837-45.
Immunogenicity of venoms from four common snakes in the south
of Vietnam and development of ELISA kit for venom detection.
J Immunol Methods 2003; 282 (1-2) :13-31.
Wei S, Ong WY, Thwin MM, Fong CW, Farooqui AA, Gopalakrishnakone
P, Hong W
Group IIA secretory phospholipase A2 stimulates exocytosis and
neurotransmitter release in pheochromocytoma-12 cells and
cultured rat hippocampal neurons. Neuroscience 2003; 121 (4)
: 891-8.
Lin VC, Jin R, Tan PH, Aw SE, Woon CT, Bay BH
Progesterone induces cellular differentiation in MDA-MB-231
breast cancer cells transfected with progesterone receptor
complementary DNA. Am J Pathol. 2003;162 (6) : 1781-7.
Du HY, Bay BH, Olivo M
Biodistribution and photodynamic therapy with hypericin in a
human NPC murine tumor model. Int J Oncol. 2003;22 (5):
1019-24.
Nirthanan S, Charpantier E, Gopalakrishnakone P, Gwee MC, Khoo HE,
Cheah LS, Kini RM, Bertrand D
Neuromuscular effects of candoxin, a novel toxin from the venom
of the Malayan krait (Bungarus candidus). Br J Pharmacol. 2003;
139 (4) : 832-44.
Nirthanan S, Gopalakrishnakone P, Gwee MC, Khoo HE, Kini RM
Non-conventional toxins from Elapid venoms. Toxicon 2003; 41(4)
: 397-407. Review.
Phan TT, Lim IJ, Bay BH, Qi R, Longaker MT, Lee ST, Huynh H
Role of IGF system of mitogens in the induction of fibroblast
proliferation by keloid-derived keratinocytes in vitro. Am J Physiol
Cell Physiol. 2003;284 (4) : C860-9.
Ananth C, Gopalakrishnakone P, Kaur C
Protective role of melatonin in domoic acid-induced neuronal
damage in the hippocampus of adult rats. Hippocampus 2003;
13 (3) : 375-87.
Ananth C, ST Dheen, Gopalakrishnakone P, Kaur C
Distribution of NADPH-diaphorase and expression of nNos, NMethyl-D-Aspartate (NMDAR1) and Non-NMDA glutamate
receptor (GlutR2) genes in the neurons of the hippocampus
following Domoic Acid-induced lesions in adult rats. Hippocampus
2003; 13 : 260-72.
Faculty of Medicine Research Report 2003
Rodriguez I, Lesaicherre M, Tie Y, Zou Q, Yu C, Singh J, Meng LT, Uppili
S, Li SF, Gopalakrishnakone P, Selvanayagam ZE
Practical integration of polymerase chain reaction amplification
and electrophoretic analysis in microfluidic devices for genetic
analysis. Electrophoresis 2003; 24(1-2) : 172-8.
Paaventhan P, Joseph JS, Nirthanan S, Rajaseger G, Gopalakrishnakone
P, Kini MR, Kolatkar PR
Crystallization and preliminary X-ray analysis of candoxin, a novel
reversible neurotoxin from the Malayan krait Bungarus candidus.
Acta Crystallogr D Biol Crystallogr. 2003; 59(3) : 584-6.
Batulan Z, Shinder GA, Minotti S, He BP, Doroudchi MM, Nalbantoglu
J, Strong MJ, Durham HD
High threshold for induction of the stress response in motor
neurons is associated with failure to activate HSF1. J Neurosci.
2003; 23(13) : 5789-98.
19
Arundine M, Sanelli T, He BP, Strong MJ
NMDA induces NOS 1 translocation to the cell membrane in NGFdifferentiated PC 12 cells. Brain Res. 2003; 976(2) : 149-58.
Strong MJ, Sopper MM, He BP
In vitro reactive nitrating species toxicity in dissociated spinal
motor neurons from NFL (-/-) and hNFL (+/+) transgenic mice.
Amyotroph Lateral Scler Other Motor Neuron Disord. 2003; 4 :
81-9.
Yap CC, Liang F, Yamazaki Y, Muto Y, Kishida H, Hayashida T, Hashikawa
T, Yano R
CIP98, a novel PDZ domain protein, is expressed in the central
nervous system and interacts with calmodulin-dependent serine
kinase. J Neurochem. 2003; 85 : 123-134.
Lu J, S Moochhala, M Shirhan, KC Ng, AL Teo, MH Tan, XL Moore, MC
Wong, EA Ling
Neuroprotection by aminoguanidine after lateral fluid-percussive
brain injury in rats : a combined magnetic resonance imaging,
histopathologic and functional study. Neuropharmacology, 2003;
44 : 253-63.
Lan CT, LC Hsu, CN Cheng, HL Chuang, EA Ling
Synaptic remodeling in the dorsal motor nucleus of the vagus
nerve following vagal – hypoglossal nerve anastomosis in the
cat. J Comp Neurol, 2003; 458 : 195-207.
QD Hu, BT Ang, M Karsak, WP Hu, XY Cui, T Duka, Y Takeda, W Chia,
S Natesan, YK Ng, EA Ling, T Maciag, D Small, R Trifonva, R Kopan, H
Okano, M Nakafuku, S Chiba, H Hirai, JC Aster, M Schachner, C J. Pallen,
K Watanabe, ZC Xiao
F3/Contactin acts as a functional ligand for notch during
oligodendrocyte maturation. Cell 2003; 115 : 1-20
ET Ang, PTH Wong, S Moochhala, YK Ng
Neuroprotection associated with running: Is it a result of increased
endogenous neurotrophic factors? Neuroscience 2003; 118(2) :
335-45.
Shi L, Tang GP, Gao SJ, Ma YX, Liu BH, Li Y, Zeng JM, Ng YK, Leong KW,
Wang S
Repeated intrathecal administration of plasmid DNA complexed
with polyethylene glycol-grafted polyethylenimine led to prolonged
transgene expression in the spinal cord. Gene Ther. 2003; 10(14)
: 1179-88.
Ren MQ, Ong WY, Wang XS, Watt F
A nuclear microscopic and histochemical study of iron
concentrations and distribution in the midbrain of two age groups
of monkeys unilaterally injected with MPTP. Exp. Neurol. 2003;
184(2) : 947-54.
Farooqui AA, Ong WY, Horrocks LA
Plasmalogens, docosahexaenoic acid and neurological disorders.
Adv Exp Med Biol. 2003;544 : 335-54.
Lu J, S Moochhala, M Shirhan, KC Ng, MH Tan, AL Teo and EA Ling
Nitric oxide induces macrophage apoptosis following traumatic
brain injury in rats. Neuroscience Lett. 2003; 339 : 147-50.
McRae A, EA Ling
Cerebrospinal fluid and serum anti-microglial antibodies : prospects
for early diagnosis of Alzheimer’s disease. Expert Review of
Neurotherapeutics, 2003; 3 : 89-99.
Chin CM, J Hu, EA Ling, MK Li, D Png
The effect of chronic bladder outlet obstruction on expression of
nitric oxide synthase in the guinea pig bladder wall to study its
relationship to detrusor instability. Euro Urol, 2003; 1: 219.
(European Urology Supplement 2).
Hsu J, YS Lee, CN Chang, HL Chuang, EA Ling, CT Lan
Sleep deprivation inhibits expression on NADPH-d and NOS while
activating microglia and astroglia in the rat hippocampus. Cells
Tissues Organs, 2003; 173, (4) : 242-54.
DY Nie, ZH Zhou, BT Ang, FYH Teng, G Xu, T Xiang, CY Wong, L Zeng, Y
Takeda, TL Xu, YK Ng, C Faivre-Sarrailh, B Popko, EA Ling, M Schachner,
K Watanabe, CJ Pallen, BL Tang, ZC Xiao
Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation
of K+ channel localization. The EMBO Journal 2003; 22 (21):
5666-5678
20
Ong WY, Lu XR, Horrocks LA, Farooqui AA, Garey LJ
Induction of astrocytic cytoplasmic phospholipase A2 and neuronal
death after intracerebroventricular carrageenan injection, and
neuroprotective effects of quinacrine. Exp. Neurol. 2003; 183 (2)
: 449-57.
Ong WY, Goh EW, Lu XR, Farooqui AA, Patel SC, Halliwell B
Increase in cholesterol and cholesterol oxidation products, and
role of cholesterol oxidation products in kainate-induced neuronal
injury. Brain Pathol. 2003;13 (3) : 250-62.
Wang XS, Ong WY, Connor JR
Quinacrine attenuates increases in divalent metal transporter-1
and iron levels in the rat hippocampus, after kainate-induced
neuronal injury. Neuroscience 2003;120 (1) : 21-9.
Thwin MM, Ong WY, Fong CW, Sato K, Kodama K, Farooqui AA,
Gopalakrishnakone P
Secretory phospholipase A2 activity in the normal and kainate
injected rat brain, and inhibition by a peptide derived from python
serum. Exp Brain Res. 2003; 150 (4) : 427-33.
Ong WY, Lu XR, Ong BK, Horrocks LA, Farooqui AA, Lim SK
Quinacrine abolishes increases in cytoplasmic phospholipase A2
mRNA levels in the rat hippocampus after kainate-induced
neuronal injury. Exp Brain Res. 2003; 148 (4) : 521-4.
Faculty of Medicine Research Report 2003
Staff Profile
Professor and Head
Professor
:
:
Ling Eng Ang
P Gopalakrishnakone
Associate Professors
:
Assistant Professors
:
Teaching Assistant
Professorial Fellow
Part-time Tutors
:
:
:
Adjunct Staff
:
Bay Boon Huat
Charanjit Kaur
K Rajendran
Ong Wei Yi
Tay Sam Wah, Samuel
Voon Chee Tet, Francis
He Beiping
Liang Fengyi
Ng Yee Kong
S Thameem Dheen
Yip Wai Cheong, George
S Dinesh Kumar
Sit Kwok Hung
Chia Chin Soon, John
Gurmit Singh
Wong Wai Chow
Leung King Chor, Thomas
Lu Jia
Tan Puay Hoon
Tang Feng Ru
Xiao Zhicheng
Research Fellows
:
Research Assistants
:
Anita S Jayasurya
Kellathur Nadathur Srinivasan
Koilan Subramaniyan
Maung Maung Thwin
Chu Haiying
Fu Di
Gao Qing
HSR Prasad
Kandasamy Matheswaran
Le Khac Quyen
Liao Dongmei
R Perumal Samy
Viswanathan Sivakumar
Zhang Bin
Contact Information
Contact Person
:
Telephone
Facsimile
Email
Postal Address
:
:
:
:
Homepage
:
Prof Ling Eng Ang
Head, Department of Anatomy
6874-3200
6778-7643
anthead@nus.edu.sg
Department of Anatomy
Faculty of Medicine
National University of
Singapore, Singapore 117597
http://www.med.nus.edu.sg/
ant/index.htm
Faculty of Medicine Research Report 2003
21
MISSION STATEMENT
DEPARTMENT OF
Biochemistry
“To enhance the international stature of NUS and Singapore through
excellence in research, teaching and scholarship in biochemistry, cell and
molecular biology”
UNDERGRADUATE AND
POSTGRADUATE PROGRAMMES
In addition to teaching in the medical and dental courses, the Department
offers General Education Modules and undergraduate Life Sciences
courses leading to BSc and BSc Honours with majors in Biomedical
Sciences and Molecular Biology. The degrees of Master of Science (MSc)
and Doctor of Philosophy (PhD) are awarded on the basis of independent
but supervised research and coursework. Most postgraduate students
are supported by NUS research scholarships/studentships. The Department
also provides research attachments for students from junior colleges
(Science Research Programme), polytechnics (Training Programme), NUS
undergraduates (Undergraduate Research Opportunities Programme in
Science and Medicine), University Scholars Programme and overseas
undergraduates and visiting scientists. The Department also actively
participates in the activities of NUS Graduate School for Integrative
Sciences and Engineering (NGS).
RESEARCH
The Department is well equipped for research. The main areas of
research include:
Biochemistry of free radicals and antioxidants;
Biochemistry and molecular biology of venoms and toxins;
Biochemistry and biophysics of membranes and lipoproteins;
Biochemistry of ubiquitination and the proteasome, especially in
relation to neurodegenerative disease;
Detoxification and drug metabolising enzymes;
Intracellular protein trafficking;
Lipidomics, Proteomics and Transcriptomics;
Molecular neurobiology;
Mammalian signal transduction and regulation of apoptosis;
Molecular biology of bacterial and viral pathogens;
Sterol metabolism and atherosclerosis;
Tumour immunology.
The Department has established collaborative research with many overseas
groups, other departments and research institutes within and outside
NUS, with government departments and private industries. Staff members
also hold joint appointments in University of Melbourne, University of
London, Institute of Molecular and Cell Biology (IMCB), National Cancer
Centre and Johns Hopkins University School of Medicine. Staff from
institutions such as IMCB, Bioinformatics Institute, Johns Hopkins
Singapore, ES Cell International Pte Ltd, Singapore General Hospital,
National Neuroscience Institute and the National Cancer Centre hold
adjunct appointments in the Biochemistry Department.
22
Faculty of Medicine Research Report 2003
Project Description
Grants Awarded in 2003
Substrate specificity and substrate recognition by MRP4
and MRP5
Principal Investigator
: Dr Theresa Tan
Syntaxins at the trans-golgi network/endosome and their roles
in neuronal/glial membrane traffic
Redox dependence of Bcl-2
Principal Investigator
Principal Investigator
Functions of small GTPases and their Interacting Partners in
the brain
: Dr Jeffrey Armstrong
: Dr Tang Bor Luen
Functional roles of CD38/ADP-ribosyl cyclase and its metabolites
in the rat models of liver cirrhosis
Principal Investigator
Principal Investigator
Nitroproteomics: A novel approach towards the understanding
of nitrosative stress and NO regulation in cellular processes and
human diseases
: Assoc Prof Chang Chan Fong
Host pathogen interaction in infection by Burkholderia
pseudomallei
Principal Investigator
: Dr Gan Yunn Hwen
Establishing and identifying important dietary and TCM –based
antioxidants in the human body
Principal Investigator
Principal Investigatior
Principal Investigator
: Assoc Prof Khoo Hoon Eng
: Dr Song Jianxing
Synthetic minimized ribozymes and double-stranded RNA
interference (RNAi) approaches for sequence-specific control of
Hepatitis B viral gene expression
Principal Investigator
: Dr Yeong Foong May
: Prof Barry Halliwell
Understanding the dynamic nature of the gradual unfolding of
CHABII and designing functional mimetics for protein-protein
interaction between EphrinB2 and its binding partner
Principal Investigator
: Dr Matthew Whiteman
The role of chromosome condensation in maintenance of
genomic stability
Ongoing Projects
Mitochondrial DNA polymorphisms from ancient skeletons
Principal Investigator
: Dr Tang Bor Luen
Studies of function and regulation of human ADP-ribosyl cyclases
in normal and abnormal cells using inducible adenoviral gene
expression system
Principal Investigator
: Assoc Prof Chang Chan Fong
Expression cloning and functional expression of a novel
endogenous ligand of human Bone Marrow Stromal
Antigen 1/CD157
Principal Investigator
: Assoc Prof Chang Chan Fong
: Dr Theresa Tan
Dr Whiteman – Expert on Nitric Oxide and Free Radicals in NUS
Faculty of Medicine Research Report 2003
Preparing vials for injection into GCMS
23
Oxidative stress-induced cell injury in neurodegenerative
diseases: Investigations of the involvement of ubiquitinproteasome pathway in excitotoxicity and amyloid ß-peptide
mediated neuronal apoptosis
Principal Investigator
: Dr Steve Cheung Nam Sang
Membrane proteins and drug resistance in Burkholderia
pseudomallei
Principal Investigator
Principal Investigator
Co-Principal Investigator
: Dr Gan Yunn Hwen
: Dr Chua Kim Lee
: Dr Steve Cheung Nam Sang
Oxidative stress in neuronal injury: Functional genomic and
proteomic analysis in cultured neurons from genetically
manipulated mice
Principal Investigator
Identification of virulence factors and vaccine candidates in
Burkholderia pseudomallei
Signal transduction pathways mediated by Mycobacterial Heat
Shock Protein 65
Principal Investigator
: Dr Gan Yunn Hwen
Inhibition of proteasomal function as a mechanism of cell death
in neurodegenerative disease. Induction by reactive oxygen species
and the role of nitric oxide
Principal Investigator
: Prof Barry Halliwell
: Dr Chua Kim Lee
Diet-dependent mechanisms of colonic damage and protection
Proteomics in human diseases: Application to hepatocellular
carcinoma (HCC)
Principal Investigator
Principal Investigator
Age-related diseases, iron and oxidative damage. The
cholesterol-fed rabbit as a model of atherosclerosis and
neurodegenerative disease
: Assoc Prof Chung Ching Ming, Maxey
Regulation of tumor cell response to apoptosis by reactive
oxygen intermediates
Principal Investigator
Principal Investigator
: Prof Barry Halliwell
: Prof Barry Halliwell
: Dr Marie-Véronique Clément
Expression and functional studies on venom nerve growth factor
Investigate superoxide anion dependent survival pathway(s) in
tumour cells
Principal Investigator
Principal Investigator
Agonists and antagonists of aquaporins and related ion channels
from toxins
: Dr Marie-Véronique Clément
: Prof K Jeyaseelan
Intracellular Acidification and Decrease in Superoxide Anion:
Novel mechanism for Bypassing Bcl-2 Protection in Tumor cells
Principal Investigator
Principal Investigators
Anti-microbial and anti-parasitic peptides in Scorpion hemolymph
and venom
: Dr Marie-Véronique Clément,
Assoc Prof Shazib Pervaiz
Determination of the 3-dimensional structure of the kinase
domain of isozymes of protein kinase C superfamily kinases by
X-ray cystallography
Principal Investigator
Principal Investigator
: Prof K Jeyaseelan
Procoagulant phospholipase A2 from snake venoms
Principal Investigator
Co-Principal Investigator
: Dr Duan Wei
: Prof K Jeyaseelan
: Prof K Jeyaseelan
: Dr A Armugam
Pharmacological characterisation of a lethal factor (Stonustoxin,
SNTX) from Stonefish venom
Principal Investigator
: Assoc Prof Khoo Hoon Eng
Strategies to improve co-expression of multiple genes for gene
therapy with internal ribosome
Principal Investigator
: Dr Caroline Lee Guat Lay
Identification of the proteins involved in intracellular trafficking
of lysosomal/late endosomal cholesterol
Principal Investigator
: Assoc Prof Li Qiu-Tian
Life Sciences Lab 8 (MD7)
24
Faculty of Medicine Research Report 2003
Liposome-encapsulated drugs for delivery to the brain
Principal Investigator
Towards a bioartificial kidney device
Principal Investigator
Co-Principal Investigator
: Prof Sit Kim Ping
: Dr Theresa Tan
NMR-based design and discovery of drug-like molecules
for EPH receptor-ephrinB mediated signalling network
controlling embryonic patterning, neuronal targeting and
human tumor development
Principal Investigator
: Dr Song Jianxing
Role of adenosine in cell death
Principal Investigator
: Assoc Prof Tan Chee Hong
Liposome-ATPase complexes for the study of palytoxin action
Principal Investigator
: Assoc Prof Tan Chee Hong
Transport of sulphate conjugates
Principal Investigator
: Dr Theresa Tan
Molecular, cellular and preclinical investigations of molecules
involved in inhibition of CNS neuronal regeneration.
Principal Investigator
: Dr Tang Bor Luen
Molecular characterization of alternatively spliced GFR-2
receptor isoforms
Principal Investigator
International Publications
: Assoc Prof Li Qiu-Tian
Charmian, Cher, DN., Armugam, A., Lachumanan, R., Wintour-Coghlan,
M. and Jeyaseelan, K
Pulmonary inflammation and edema induced by phospholipase
A2: Global gene-analysis and effects on aquaporins and Na+/K+
ATPase. Journal of Biological Chemistry, (2003)278: 352-31360.
Chai, PC., Long, LH. and Halliwell, B
Contribution of hydrogen peroxide to the cytotoxicity of green
tea and red wines. Biochemical, and Biophysical Research
Communications (2003) 304 : 650-654.
Chua, K L, Y Y Chan and Gan Y H
Flagella: A virulence determinant in Burkholderia pseudomallei.
Infection and Immunity, (2003) 71:1622-1629.
Clement, M V, Hirpara, J L and Pervaiz, S
Decrease in intracellular superoxide sensitizes Bcl-2-overexpressing
tumor cells to receptor and drug-induced apoptosis independent
of mitochondria. Cell Death and Differentiation, (2003)10 :
1273-1285.
Giannakis, E, Jokiranta T S, Male D A, Ranganathan S, Ormsby R J,
Fischetti V A, Mold C and Gordon D L
A common site within factor H SCR 7 responsible for binding
heparin, C-reactive protein and streptococcal M protein. European.
Journal of Immunology, (2003) 33: 962-969.
: Assoc Prof Too Heng-Phon
Go, M L and Li Q T
Nitric oxide and peroxynitrite in ageing: Mediators of bone and
cartilage damage in osteoporosis and osteoarthritis?
Principal Investigator
: Dr Matthew Whiteman
Identification of the molecular mechanism by which free radicals
and other reactive species affect cells from human joints: Relevance
to the pathology of rheumatoid arthritis and osteoathritis
Principal Investigator
: Dr Matthew Whiteman
Functional analysis of Ncr1p & Vps4p in endocytic sterol sorting
and transport in yeast
Principal Investigator
: Dr Robert Yang Hongyuan
Functional analysis of Ncr1p, a NPC1 ortholog in the yeast
Saccharomyces cerevisia
Principal Investigator
Interaction of the antimalarial agents halofantrine and
lumefantrine with lipid bilayers. Chemical & Pharmaceutical
Bulletin, (2003) 51: 241-246.
Gwee, P C, Tang K, Chua J M, Lee E J D, Chong S S and Lee C G
Simultaneous Genotyping of Seven Single Nucleotide
Polymorphisms (SNPs) in the MDRI gene by Single Tube Multiplex
Minisequencing. Clinical Chemistry, (2003) 49: 672-676.
Halliwell, B
Oxidative stress in cell culture: an under-appreciated problem?
FEBS Letters, (2003) 540: 3-6.
Halliwell, B
Plasma antioxidants. Health benefits of eating chocolate? Nature
(2003) 426: 787-788.
: Dr Robert Yang Hongyuan
Hyun DM, Lee MH, Halliwell B and Jenner, P
Proteasomal inhibition causes the formation of protein aggregates
containing a wide range of proteins, including nitrated proteins.
Journal of Neurochemistry, (2003) 86 : 363-373.
Faculty of Medicine Research Report 2003
25
Jeyaseelan K, Poh SL, Nair R, Armugam A
Ong W Y, Goh W S, Lu X R, Farooqui A A, Patel S C and Halliwell B
Structurally conserved alpha-neurotoxin genes, encode functionally
diverse proteins in the venom of Naja sputatrix. FEBS Letters,
(2003) 533 :333-341.
Increase in cholesterol and cholesterol oxidation products, and
role of cholesterol oxidation products in kainate-induced neuronal
injury. Brain Pathology, (2003) 13: 250-262.
Khoo H E
Peng T, Liu ZM, Yan LN, Peng MH, Li LQ, Liang RX, Wei ZL, Halliwell B
and Ong CN
Implementation of problem-based learning in Asian medical
schools and students' perceptions of their experience. Medical
Education, (2003) 37: 401-409.
Lee C G L, Ren J, Cheong, I SY, Jin,R, Ban, K HK, Ooi, L LPJ, Nuchprayoon,
I, Lee K-H, Dang MC, Dang CV and Lee L L
Oxidative DNA damage in peripheral leukocytes and its association
with expression and polymorphisms of hOGG(1): A study of
adolescents in a high risk region for hepatocellular carcinoma in
China. World Journal of Gasteroenterology, (2003) 9: 2186-2193.
Expression of the FAT10gene is highly up-regulated in
hepatocellular carcinoma and other gastrointestinal and
gynecological cancers. Oncogene, (2003) 22: 2592-2603.
Poon KL, Richardson M, Lam CS, Khoo H E and Korzh V
Lim Y P, Hoog JO, Gardner P, Ranganathan S, Andersson S, Subbiah S,
Tan T W, Hide W and Weiss AS
Rawlingson A, Shendi K, Greenacre S A, England T G, Jenner A M, Poston
R N, Halliwell B. and Brain S D
The S-Star trial bioinformatics course - An on-line learning
success. Biochemistry and Molecular Biology Education, (2003)
31: 20-23.
Functional significance of inducible nitric oxide synthase induction
and protein nitration in the thermally injured cutaneous
microvasculature. American Journal of Pathology, (2003) 162:
1373-1380.
Expression pattern of neuronal nitric oxide synthase in embryonic
zebrafish. Gene Expression Pattern, (2003) 3 : 463-466.
Lee B T K, Tan T W and Ranganathan S
MGAlignIt: a web service for the alignment of mRNA/EST
and genomic sequences. Nucleic Acids Research, (2003) 31:
3533-3536.
Rose P, Whiteman M, Huang SH, Halliwell B and Ong CN
ß- phenylethyl isothiocyanate-mediated apoptosis in hepatoma
HepG2 cells. CMLS, Cellular and Molecular Life Science (2003)
60: 1489-1503.
Liu H, Armugam A, Jeyaseelan K, Kouloulas I and Wintour E M
Aquaporin gene expression and regulation in the ovine fetal lung.
Journal of Physiology – London, (2003) 551: 503-514.
Selvanayagam N, Gopalakrishnakone P, Gwee M C E, Khoo H E and
Kini R M
Non-conventional toxins from Elapid venoms. Toxicon, (2003) 41:
397-407.
Minqin R, Watt F, Huat BTK and Halliwell B
Correlation of iron and zinc levels with lesion depth in newlyformed atherosclerotic lesions. Free Radical Biology and Medicine,
(2003) 34 : 746-752.
Minqin R, Watt F, Tan BKH and Halliwell B
Trace elemental distributions in induced atherosclerotic lesions
using nuclear microscopy. Nuclear Instruments and Methods in
Physics Research B ,(2003) 210: 336-342.
Nie D Y, Zhou Z H, Ang C B T, Teng Y H F, Xu G, Xiang T, Wang C Y, Zeng
L, Takeda Y, Xu T L, Ng Y K, Faivre-Sarrailh C, Popko B, Ling E A, Schachner
M, Watanabe K, Pallen C J, Tang B L and Xiao Z C
Song J
Tyrosine-phosphorylation of the well-packed ephrinB cytoplasmic
ß- hairpin for reverse signaling. Journal of Biological Chemistry,
(2003) 278: 24714-24720.
Tan H H, Low P S, Tan Y S, Tong M C, Saha N, Yang H and Heng C K
ABCA1 gene polymorphisms and their associations with Coronary
Artery Disease and Plasma Lipids in males from 3 ethnic
populations in Singapore. Human Genetics, (2003)113 : 106-117.
Tang G P, Zeng J M, Gao S J, Ma Y X, Shi L, Li Y, Too H P and Wang S
Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation
of K+ channel localization. European Molecular Biology
Organisation Journal, (2003) 22: 5666-5678.
Polyethylene glycol modified polyethylenimine for improved CNS
Gene Transfer: Effects of PEGyclation Extent. Biomaterials, (2003)
24 :2351-2362.
Nirthanan S, Charpantier E, Gopalakrishnakone P, Gwee M C E, Khoo
H E, Cheah L S, Kini R M and Bertrand D
Too H P
Pharmacological Effects of Candoxin A Novel Toxin from the
Venom of the Malayan Krait (Bungarus candidus) at the
neuromuscular Junction. British Journal of Pharmacology, (2003)
139 : 832-844.
26
Real time PCR quantification of GFRa2 alternatively spliced
isoforms in murine brain and peripheral tissues. Brain Research
Molecular, (2003) 114: 146-153.
Faculty of Medicine Research Report 2003
Too H P
Assistant Professors
:
Research Fellows
:
Adjunct Staff
:
From genes to therapeutics: educating the government and the
public, a Singapore experience. BioEssays, (2003) 25: 913-917.
Vivek G, Tan T W and Ranganathan S
XdomView: protein domain and exon position visualization.
Bioinformatics, (2003) 19: 159-160.
Wee L M, Long L H, Whiteman M L and Halliwell B
Factors affecting the ascorbate- and phenolic-dependent
generation of hydrogen peroxide in Dulbecco's modified Eagles
medium. Free Radical Research, (2003) 37: 1123-1130.
Wei C L, Khoo H E, Lee K H and Hon W M
Enhanced expression of heme oxygenase-1 in cirrhotic liver.
Journal of Pathology, (2003) 199: 324-334.
Whiteman M, Rose P and Halliwell B
Inhibition of hypochlorous acid-induced oxidative reactions by
nitrite: Is nitrite an antioxidant? Biochemical and Biophysical
Research Communications (2003) 303: 1217-1224.
Whiteman M, Rose P, Siau JL and Halliwell B
Nitrite-mediated protection against hypochlorous acid-induced
chondrocyte toxicity. Arthritis Rheumatism (2003) 48: 3140-3150.
Whiteman M L, Siau J L and Halliwell B
Lack of tyrosine nitration by hypochlorous acid in the presence
of physiological concentrations of nitrite. Journal of Biological
Chemistry, (2003) 278: 8380-8384.
Armstrong Jeffrey
Cheung Nam Sang, Steve
Clement, Marie-Veronique
Duan Wei
Gan Yunn Hwen
Lee Guat Lay, Caroline
Liou Yih-Cherng
(jointly with DBS)
Song Jianxing (jointly with DBS)
Tan May Chin, Theresa
Tang Bor Luen (jointly with IMCB)
Wenk Markus (jointly with DBS)
Whiteman, Matthew
Yang Hongyuan, Robert
Arunmozhiarasi Armugam
Choy Meng Syan
Colin Peter Rose
Jenner, Andrew
Lee Chung-Yung Jetty
Lin Haishu
Peng Zhao Feng
Zhu Yimin
Chatterjee, Subroto
Colman, Alan
Malcom Paterson
Sven Petterson
Hong Wanjin
Cai Mingjie
Cao Xinmin
Kanaga Sabapathy
Jiang Yun Jin
Li Kuo Bin
Liu Jianhua
Ichiro Maruyama
Pawan Kuman Dhar
Gunaretnam Rajagopal
Woo WH, Yang HY, Wong KP and Halliwell B
Sulphite oxidase gene expression in human brain and in other
human and rat tissues. Biochemical and Biophysical Research
Communications (2003) 305: 619-623.
Contact Information
Contact Persons
:
Telephone
:
Facsimile
E-mail
:
:
Postal Address
:
Homepage
:
Staff Profile
Professor & Head
Professor & Deputy Head
Professor
Associate Professors
Senior Lecturer
:
:
:
:
:
Barry Halliwell
Kandiah Jeyaseelan
Sit Kim Ping
Chang Chan Fong
Chung Ching Ming, Maxey
Khoo Hoon Eng
Li Qiutian
Ranganathan, Shoba
Tan Chee Hong
Teo Tian Seng
Tan Tin Wee
Too Heng-Phon
Raghunath Michael
(jointly with BIE)
Chua Kim Lee
Faculty of Medicine Research Report 2003
27
Profs Barry Halliwell /
Kandiah Jeyaseelan
Head / Deputy Head of
Department
6874-3240
6874-3243
6874-3682
6779-1453
bchsec@nus.edu.sg /
bchaaw@nus.edu.sg
Department of Biochemistry
Faculty of Medicine
National University of
Singapore
MD7, 8 Medical Drive
Singapore 117597
http//www.med.nus.edu.sg/
bioweb/biochemistry/
homepage.htm
DEPARTMENT OF
Community, Occupational
& Family Medicine
INTRODUCTION
The Department continued with its major research emphasis on chronic
diseases (cancer and cardiovascular diseases, diabetes, myopia),
environmental and occupational health, and health services research.
In the area of cancer, the areas of interest are dietary factors and geneenvironment interactions, while in cardiovascular diseases, the focus
on obesity, genes and atherosclerosis remains. In environmental health,
major interests that have developed are the health effects
of reactive oxygen species, cancer chemoprevention, and the use of
salivary biomarkers.
28
Faculty of Medicine Research Report 2003
Project Description
Dietary and genetic factors in asthma and chronic bronchitis in
the Singapore Chinese Health Study
Principal Investigators
Grants Awarded in 2003
Collaborators
Psychological and Behavioural Responses of Healthcare Workers
in Singapore to the SARS Outbreak / The Occupational Health of
Healthcare Workers in Singapore Following the SARS Outbreak
Principal Investigators
Collaborators
: Prof David Koh,
Assoc Prof Calvin Fones
: Assoc Prof Chia Sin Eng,
Assoc Prof Lim Meng Kin
Establishing a Singapore Twin Register for Genomics Research
Principal Investigator
Collaborators
: Assoc Prof Chia Kee Seng
: Adj Assoc Prof Eric Yap,
Prof Lee Hin Peng,
Prof Edison Liu,
Adj Assoc Prof Chew Suok Kai
Ongoing Projects
-Aminolevulinic Acid Dehydratase (ALAD) polymorphism and
susceptibility of workers exposed to inorganic lead and its effects
on the haematological, renal and neurobehavioral functions
Principal Investigator
Collaborators
Principal Investigators
Principal Investigator
Collaborators
Collaborators
The Role of Dietary Isothiocyanates in Chemoprevention: A
Mechanistic Study
Principal Investigator
Collaborators
: Assoc Prof Chia Sin Eng
: Adj Assoc Prof Eric Yap,
Assoc Prof Chia Kee Seng
Concurrent Cohort Study of the Environmental and Genetic Risk
Factors for Myopia in Singapore School Children
Anti-Carcinogenic Activity of Chrysanthemum Morifolium Extract:
Nuclear Factor-Kappa B as the Molecular Target
: Dr Shen Han Ming
: Dr Xianglin Shi
(Center for Disease Control, USA),
Assoc Prof Ang Siau Gek
(Dept of Chemistry),
Assoc Prof Lai Yee Hing
(Dept of Chemistry)
: Dr Koh Woon Puay,
Dr Stephanie London
(National Institute of Environmental
Health Studies, USA)
: Prof Lee Hin Peng,
Prof Mimi Yu
(University of Southern California)
: Prof Ong Choon Nam
: Dr Matt Whiteman,
Dr Peter Rose
: Assoc Prof Saw Seang Mei,
Assoc Prof Donald TH Tan
: Dr Wu HM (DMRI),
Dr Louis Tong (SNEC),
Dr A Carkeet (SERI),
Dr Chua WH (SNEC),
Dr Hong Ching Ye,
Assoc Prof Chia Kee Seng,
Adj Assoc Prof Eric Yap (DMRI),
Prof David Koh,
Prof J Katz
(Johns Hopkins University),
Prof R A Stone
(University of Pennsylvania)
Prevalence and Risk Factors for Cataract in Sumatra, Indonesia
Principal Investigator
Co-Principal Investigators
: Assoc Prof Saw Seang Mei
: Prof David Koh,
Dr Rahat Hussein (SNEC),
Dr Alicia Fong (SNEC),
Dr Chua Wei Han (SNEC),
Dr Louis Tong (SNEC),
Dr Llewylyn Lee (SNEC),
Dr Cheng Jin Fong (SNEC),
Dr Alan Fong (SNEC),
Assoc Prof Donald Tan (SERI)
Electrophoresis of DNA products after PCR amplification
Faculty of Medicine Research Report 2003
29
Optimal Diabetes Management and Renal Complications
Prevention (transferred from Dept of Medicine in August 2000)
Principal Investigator
Collaborators
: Assoc Prof Goh Lee Gan
: Assoc Prof Ng Tze Pin,
Dr Helen Leong,
Dr Sim Li San,
Dr Elaine Tan,
Dr Yvette Tan,
Dr Tay Ee Guan
Collaborators
Principal Investigator
Collaborator
: Prof David Koh
: Prof Ong Choon Nam,
Ms Vivian Ng,
Mr Ong Her Yam,
Assoc Prof Chia Sin Eng
: Prof Lee Hin Peng
: Dr Shanta Emmanuel
(National Health Group Polyclinics)
Singapore Cardiovascular Cohort Study
: Prof David Koh,
Assoc Prof Saw Seang Mei
: Prof Ong Choon Nam,
Assoc Prof Chia Sin Eng,
Assoc Prof Wong Mee Lian,
Dr Hong Ching Ye,
Assoc Prof Adeline Seow,
Dr Jeannette Lee
Principal Investigator
Collaborators
: Dr Jeannette Lee
: Adj Assoc Prof Kenneth Hughes,
Adj Assoc Prof Chew Suok Kai
(Ministry of Health),
Dr Derrick Heng
(Ministry of Health),
Ms Tan Bee Yian
(Ministry of Health)
Effect of Feverfew on two nasopharyngeal cancer cell lines with
distinct growth characteristics and cyclooxygenase-2 expression
Carcinogenic heterocyclic amines in the Chinese diet:
development of an instrument for exposure assessment in
population-based studies
Principal Investigator
Co-Principal Investigator
Collaborators
: Prof Lee Hin Peng,
Prof Mimi C Yu
(University of Southern California)
: Dr Koh Woon Puay,
Assoc Prof Adeline Seow
World Health Organisation Development of WHO PRO Guidelines
on Prevention and Control of Non-Communicable Diseases in
Primary Health Care
Health Survey of Villagers Living in the Vicinity of a Pulp and
Paper Mill, Sumatra, Indonesia
Principal Investigators
Principal Investigators
Co-Principal Investigators
Salivary biomarkers of occupational stress
Principal Investigator
Collaborators
NUS-USC Cohort Study of Diet and Cancer
: Assoc Prof Adeline Seow
: Dr Koh Woon Puay
: Dr Zhao Bin (DMRI),
Dr Mark Knize
(University of California),
Prof Edmund Lee,
Prof Lee Hin Peng
Principal Investigator
Collaborator
Anti-cancer effects of parthenolide in human colorectal cancer
and nasopharyngeal cancer cells: involvement of cyclooxygenase2 and fatty acid synthase through the NFκB pathway.
Principal Investigators
Collaborators
Collection of saliva from children for study of stress biomarkers
: Prof Ong Choon Nam
: Dr Shen Han Ming
: Dr Shen Han Ming,
Prof Ong Choon Nam
: Dr Young Wang
(Johns Hopkins Singapore),
Prof Daniel W Chan
(Johns Hopkins Singapore),
Dr Lin Zhong Ning
(Sun Yat Sen University of Medical
Science, China)
Workplace assessment of a Sewage Treatment Plant following the
SARS outbreak
30
Faculty of Medicine Research Report 2003
The Role of Oxidative DNA Damage and Micronutrients in
Colorectal Carcinogenesis.
Principal Investigator
Collaborators
: Prof Ong Choon Nam
: Prof Barry Halliwell,
Dr Shen Han Ming
A Preliminary Investigation of Antioxidative Effects of Common
Dietary Flavonoids in a Colon Cell Line.
Principal Investigator
Collaborator
: Prof Ong Choon Nam
: Dr Shen Han Ming
D S Q Koh, M K Lim and S E Chia
SARS Health care work can be hazardous to health. Occupational
Medicine, 53, no.4 (2003): 241-243.
D S Q Koh and S M Lee
Good medical practice for occupational physicians. Occupational
and Environmental Medicine, 60 (2003): 1-2.
D S Q Koh, H Wang, J Lee, K S Chia, H P Lee and C L Goh
Sexually transmitted diseases and their associated risk behaviours
among male clients of female commercial sex workers in Singapore
Epidemiology and health services research. Basal cell carcinoma,
squamous cell carcinoma and melanoma of the skin – Analysis
of the Singapore Cancer Registry data 1968 – 1997. British Journal
of Dermatology, 148, no.6 (2003): 1161-1166.
Principal Investigator
Collaborators
D S Q Koh and T C Aw
: Assoc Prof Wong Mee Lian
: Dr Roy Chan
(National Skin Centre),
Adj Assoc Prof Chew Suok Kai
(Ministry of Health),
Dr Mark Barrett,
Prof David Koh,
Ms Sharon Wee,
Mr Thiyagarajan Jayabaskar
Surveillance in occupational health. Occupational and
Environmental Medicine, 60 (2003): 705-710.
D S Q Koh, V A C Ng, L H Chua, Y Yang, H Y Ong, S E Chia
Can salivary lead be used for biological monitoring of lead exposed
individuals? Occupational and Environmental Medicine, 60 (2003):
696-698.
International Publications
Koh W P, J M Yuan, C L Sun, D Van Den Berg, A L H Seow, H P Lee and
M C Yu
Araki S, D P K Ng, B Krolewski, L Wyrwicz, J J Rogus, L Canani, Y Makita,
M Haneda, J H Warram, A S Krolewski
Angiotensin I-converting enzyme (ACE) gene polymorphism and
breast cancer risk among Chinese women in Singapore. Cancer
Research, 63 (2003): 573-578.
Identification of a common risk haplotype for diabetic nephropathy
at the protein kinase C-beta1 (PRKCB1) gene locus. Journal of
A m e r i c a n S o c i e t y o f N e p h r o l o g y, 1 4 , n o. 8 ( 2 0 0 3 ) :
2015-2024.
S E Chia, L M Shi, O Y Chan, S K Chew and B H Foong
Parental occupations and non-chromosomal single, chromosomal
single and multiple birth defects: A population-based study in
Singapore from 1994 to 1998. American Journal of Obstetrics
and Gynecology, 188 (2003): 425-433.
C Y Hong, K Hughes, K S Chia, V A C Ng and S L Ling
Urinary alpha1-microglobulin as a marker of nephropathy in type
2 diabetic Asian subjects in Singapore. Diabetes Care, 26, no.2
(2003): 338-342.
Katz J, O D Schein, B Levy, T Cruisculllo, S M Saw, U Rajan, T K Chan,
C Y Khoo
A randomized trial of rigid gas permeable contact lenses to reduce
progression of children’s myopia. American Journal of
Ophthalmology, 136 (2003): 82-90.
Faculty of Medicine Research Report 2003
Koh W P, M B Taylor, S K Chew, M C Phoon, K L Kang, V T Chow
Chlamydia pneumoniae IgG seropositivity and clinical history of
ischemic heart disease in Singapore. Journal of Microbiol Immunol
Infect, 36, no.3, (2003): 169-174.
Leo Y S, M Chen, B H Heng, C C Lee, N Paton, B Ang, P Choo, S W Lim,
A E Ling, M L Ling, B K Tay, P A Tambyah, Y T Lim, G Gopalakrishna, S
Ma, L James, P L Ooi, S Lim, K T Goh, S K Chew, C C Tan
Severe acute respiratory syndrome – Singapore, 2003. Morbidity
and Mortality Weekly Report (MMWR), 52, no.18 (2003):
405-410.
Lim M K and D S Q Koh
SARS and occupational health in the air. Occupational and
Environmental Medicine, 60 (2003): 539-540.
Lim M K
Two horsemen of the apocalypse. Reflections on the Iraq War,
SARS and humanity’s place among the stars. Foresight, The journal
of future studies, strategic thinking and policy, 5, no.4
(2003): 3-4.
31
Lipsitch Marc, T Cohen, B Cooper, J M Robins, S Ma, L James, G
Gopalakrishna, S K Chew, C C Tan, M H Samore, D Fisman and M Murray
Transmission dynamics and control of severe acute respiratory
syndrome. Science, 300 (2003): 1966-1970.
Mak K H, K S Chia, J D Kark, T Chua, C Tan, B H Foong, Y L Lim and
S K Chew
Ethnic differences in utilization of coronary revascularization
procedures and in survival following acute myocardial infarction
in Singapore. European Heart Journal 24 (2003): 151-160.
Ruan YJ, L W Chia, A E Ling, B V Vinsensius, H Thoreau, S Y Se Thoe, J M
Chia, P Ng, P C Kuo, L Lim, T Zhang, K P Chan, L E L Oon, M L Ng, Y S
Leo, F P L Ng, E C Ren, L W Stanton, P M Long, E T Liu
Comparative full-length genome sequence analysis of 14 SARS
coronavirus isolates and common mutations associated with
putative origins of infection. The Lancet, Published online (2003):
1-7.
Saw S M, G Gazzard, K G AuEong and D S Q Koh
Utility values and myopia in teenage school students. British
Journal of Ophthalmology, 87 (2003): 341-345.
Ng D P K, J H Warram and A S Krolewski
Transforming growth factor-beta1 as a genetic susceptibility locus
for advanced diabetic nephropathy in type 1 diabetes mellitus:
An investigation of multiple known DNA sequence variants.
American Journal of Kidney Diseases, 41 (2003): 22-28.
Saw S M, G Gazzard, D S Friedman, P J Foster, J Devereux, M L Wong
and S Seah
Awareness of glaucoma and health beliefs of patients suffering
primary acute angle-closure. British Journal of Ophthalmology,
87 (2003): 446-449.
Ng D P K, J H Warram, A S Krolewski
To: Rippin JD, Patel A, Belyaev ND, Gill GV, Barnett AH. Bain SC (2003)
Nitric oxide synthase gene polymorphisms and diabetic
nephropathy. Diabetologia, 46: 426-428. Diabetologia, 46, no.12
(2003): 1706.
Saw S M, D T H Tan
Interventions to retard myopia progression. Author’s reply.
Ophthalmology, 110 (2003): 1287-1288.
Saw S M, H Rahat, G Gazzard, D S Q Koh, D Widjaja, D T H Tan
Ng S C, J M Gomez, V S Rajadurai, S M Saw, S H Quak
Establishing enteral feeding in preterm infants with feeding
intolerance: a randomized controlled study of low-dose
erythromycin. Journal of Pediatric Gastroenterol Nutrition, 27,
no.5 (2003): 554-558.
Causes of low vision and blindness in rural Indonesia. British
Journal of Ophthalmology, 87 (2003): 1075-1078.
Saw S M, C Y Hong, J Lee, M L Wong, M F Chan, A Cheng, K H Leong
Awareness and health beliefs of women towards osteoporosis.
Osteoporosis International, 14, no.7 (2003): 595-601.
Ng T P, M L Wong, C Y Hong, K T Koh, L G Goh
The use of complementary and alternative medicine by asthma
patients. QJM, 96 (2003): 747-754.
Saw S M, G Gazzard, D Friedman
Interventions for angle closure glaucoma: An evidence-based
update. Ophthalmology, 110 (2003): 1869-1878.
Ng V A C, D S Q Koh, Q Fu, S E Chia
Effects of storage time on stability of salivary immunoglobulin
A and lysozyme. Clinica Chimica Acta, 338 (2003): 131-134.
Ng V A C, D S Q Koh, S E Chia
Examination stress, salivary cortisol and academic performance.
Psychological Reports, 93 (2003): 1133-1134.
Saw S M
A synopsis of the prevalence rates and environmental risk factors
for myopia. Clinical Exp. Optometry, 86 (2003): 289-294. (Invited
Review).
Ng V A C, D S Q Koh, B Mok, S E Chia, L P Lim
Suk, W A, K M Ruchirawat, K Balakrishnan, M Berger, D Carpenter, T
Damstra, J Pronczuk de Garbino, D S Q Koh, P J Landrigan, I Makalinao,
P D Sly, Y Xu, B S Zheng
Salivary biomarkers associated with academic assessment stress
among dental undergraduates. Journal of Dental Education, 67,
no.10 (2003): 1091-1094.
Environmental threats to children’s health in Southeast Asia and
the Western Pacific. Environmental Health Perspectives, 111,
no.10 (2003): 1340-1347.
Phua K H
Tai E S, J M Ordovas, D Corella, M A M P Yap, E Chan, X Adiconis, S K
Chew, L M Loh and C E Tan
Health care financing in the Asia-Pacific region. Public
Administration and Policy, 11, no.2 (2003): 13-36.
32
The TaqIB and -629C - A polymorphisms at the cholesterol ester
transfer protein locus. Associations with lipid levels in a multiethnic population. The 1998 Singapore National Health Survey.
Clinical Genetics, 63, no.1 (2003): 19-30.
Faculty of Medicine Research Report 2003
Tan Y K, T C Wee, W P Koh, Y T Wang, P Eng, W C Tan and A L H Seow
Wong H L, A Seow, K Arakawa, H P Lee, MC Yu, S A Ingles
Survival of patients with lung cancer: A comparison by staging,
histology and smoking status among Chinese women in Singapore.
Lung Cancer, 40 (2003): 237-246.
Vitamin D receptor start codon polymorphism and colorectal
cancer risk: effect modification by dietary calcium and fat in
Singapore Chinese. Carcinogenesis, 24 (2003): 1091-1095.
Wang H, K S Chia, W B Du, J J Lee, R Sankaranarayanan, R Sankila, I
Sng, A L H Seow and H P Lee
Wong M L, I Lubek, B D Chemn, S Kros, S Pen and M Chhit
Population-based survival for cervical cancer in Singapore, 19681992. American Journal of Obstetrics and Gynecology, 188 (2003):
324-329.
Social and behavioural factors associated with condom use among
direct sex workers in Siem Reap. Sexually Transmitted Infections,
79, no.2 (2003): 163-165.
Wong T Y and D T H Tan
Wilder-Smith A, K T Goh, T M S Barkham and N I Paton
Virulence of the Hajj associated W135 outbreak strain: estimates
of attack rate in a defined population and the risk of developing
invasive disease in carriers. Clinical Infectious Diseases, 36 (2003):
679-683.
Wilder-Smith A and K T Goh
The SERI-ARVO meeting and future challenges of ophthalmic
research in Asia. British Journal of Ophthalmology, 87 (2003),
379-380.
Wong T Y, R Klein, A R Sharrett, T A Manolio, L D Hubbard, E K Marino,
L Kuller, G Burke, R P Tracey, J F Polak, J S Gottdiener and D S Siscovick
W135 meningococcal disease in a traveler: A case report. Journal
of Travel Medicine, 10 (2003): 59.
The prevalence and risk factors of retinal microvascular
abnormalities in older people: The Cardiovascular Health Study.
Ophthalmology, 110 (2003): 658-666.
Wilder-Smith A and Ziad Memish
Wong T Y, P J Foster, G J Johnson and S K L Seah
Meningococcal disease and travel. International Journal of
Antimicrobial Agents, 21 (2003): 102-106.
Refractive errors, ocular dimensions and age-related cataract:
The Tanjong Pagar Survey. Investigative Ophthalmology and Visual
Sciences, 44 (2003): 1479-1485.
Wilder-Smith A
W135 meningococcal carriage in Hajj pilgrims: The Singapore
experience. International Journal of Antimicrobial Agents, 2 (2003):
112-115.
Wong T Y, B E K Klein, R Klein, M Knudtson and K Lee
Wilder-Smith A, T M S Barkham, A Earnest and N I Paton
Wu, A H, A L H Seow, K Arakawa, D Van Den Berg, H P Lee and M C Yu
Meningococcal carriage in returning Umra pilgrims from Saudi
Arabia. Journal of Travel Medicine, 10 (2003): 147-149.
HSD17B1 and CYP17 polymorphisms and breast cancer risk among
Chinese women in Singapore. International Journal of Cancer,
104, no.4 (2003): 450-457.
Refractive errors, intraocular pressure and glaucoma.
Ophthalmology, 110 (2003): 211-217.
Wilder-Smith A, T M S Barkham, S Ravindran and N I Paton
Persistence of W135 N. meningitides carriage in returning Hajj
pilgrims: Risk of early and late transmission to household contacts.
Emergency Infectious Diseases, 9, no.1 (2003): 123-126.
Yap W H, A W N Tay, S Brenner and B Venkatesh
Molecular cloning of the pufferfish (Takifugu rubripes) Mx gene
and functional characterization of its promoter. Immunogenetics,
54 (2003): 705-713.
Wilder-Smith A, T Barkham, S K Chew and N I Paton
Absence of N meningitidis W135 of the electrophoretic type 36
in pilgrims returning from the year 2002 Hajj. Emerging Infectious
Diseases, 9, no.6 (2003).
Zhang M Z, A S M Lim and T Y Wong
A pilot study of lens extraction in the management of acute
primary angle-closure glaucoma. American Journal of
Ophthalmology, 135 (2003): 534-536.
Wilder-Smith A
Current status of ‘essential obstetric care’ activities internationally:
A literature review. Tropical Doctor, 33, no.3 (2003): 135-138.
Faculty of Medicine Research Report 2003
33
Staff Profile
Professor & Head
Professors
:
:
Associate Professors
:
Assistant Professors
Clinical Associate Professors
:
:
Joint Professor (with GIS)
:
Joint Associate Professor
(with Dept of Psychological Medicine) :
Joint Associate Professor
(with Dept of Ophthalmology)
:
Adjunct Professor
:
Adjunct Associate Professors
:
Adjunct Senior Research Fellows
:
Adjunct Fellows
:
Contact Information
Koh Soo Quee, David
Lee Hin Peng
Ong Choon Nam
Chia Kee Seng
Chia Sin Eng
Goh Lee Gan
Lim Meng Kin
Phua Kai Hong
Saw Seang Mei
Seow Ling Hui, Adeline
Wong Mee Lian
Koh Woon Puay
Lee Jen Mai, Jeannette
Ng Peng Keat, Daniel
Shen Han Ming
Goh Kee Tai
Emmanuel, Shanta
Liu, Edison TB
For higher degrees by research:
Contact Person
Telephone
Facsimile
Email
:
:
:
:
Prof Ong Choon Nam
6874-4982
6779-1489
cofongcn@nus.edu.sg
For taught programmes:
(a) MMed (Public Health)
Contact Person
Telephone
Facsimile
Email
:
:
:
:
Assoc Prof Lim Meng Kin
6874-4981
6779-1489
coflimmk@nus.edu.sg
(b) MMed (Occupational Medicine)
Contact Person
Telephone
Facsimile
Email
:
:
:
:
Assoc Prof Chia Sin Eng
6874-4970
6779-1489
cofcse@nus.edu.sg
Ng Tze Pin
(c) MMed (Family Medicine)
Contact Person
Telephone
Facsimile
Email
:
:
:
:
Assoc Prof Goh Lee Gan
6874-4978
6779-1489
cofgohlg@nus.edu.sg
Wong Tien Yin
Jean-Paul M F Deslypere
Chan Nang Fong
Chan, Roy
Cheong Pak Yean
Chew Suok Kai
Hughes, Kenneth
Lee Hock Siang
Lee, Lionel KH
Lim Lean Huat
Wilder-Smith, Annelies
Yap, Eric
Yap, Mabel
Cheah Peh Yean
Alice Tay
Chan, Gregory
Chin Khong Wee, Justin
Tan Say Beng
For research centres/units:
(a) Centre for Environmental and Occupational Health Research
Contact Person
:
Prof Ong Choon Nam
Telephone
:
6874-4982
Facsimile
:
6779-1489
Email
:
cofongcn@nus.edu.sg
34
(b) Centre for Molecular Epidemiology
Contact Person
:
Telephone
:
Facsimile
:
Email
:
Assoc Prof Chia Kee Seng
6874-4971
6779-1489
cofcks@nus.edu.sg
(c) Health Service Research
Contact Person
Telephone
Facsimile
Email
:
:
:
:
Assoc Prof Phua Kai Hong
6874-4984
6779-1489
cofpkh@nus.edu.sg
For all other enquiries:
Contact Person
:
Telephone
Facsimile
Email
:
:
:
Prof David Koh
Head, Department of
Community, Occupational and
Family Medicine
6874-4988/9
6779-1489
cofhead@nus.edu.sg
Postal Address
:
Homepage
:
Faculty of Medicine Research Report 2003
Faculty of Medicine (MD3)
National University of
Singapore
16 Medical Drive
Singapore 117597
http://www.med.nus.edu.sg/
cof/cofintro.htm
DEPARTMENT OF
STRATEGIC RESEARCH INITIATIVES
Diagnostic Radiology
Our Department’s research is strongly multidisciplinary, a feature of
Radiology both as a clinical specialty and a research discipline. We have
established research collaborations with departments in Medicine as
well as Engineering.
Our research revolves around two main themes:
1. Breast Cancer Imaging & Biology
2. Advanced Image Reconstruction & Quantitation
However, there are also other individual areas of specific research
enquiry, viz.,
1. Development & validation of functional Magnetic Resonance Urography
in children
2. Development of a paediatric Asian bone age atlas
The clinical work and research of our Department is intricately entwined
with that of the Department of Diagnostic Imaging in the National
University Hospital. As such, most of our research involves collaboration
between the University and Hospital departments and their staff, and is
difficult to completely separate.
SUMMARY
The Department of Diagnostic Radiology is based within the Department
of Diagnostic Imaging at the National University Hospital. As such it has
access to state of the art imaging equipment for both normal and
abnormal human imaging, in any part of the body. It is also a very busy
clinical department, and thus has access to a wealth of clinical material
for imaging-based research in many different key conditions, notably
breast and other cancers, cardiovascular diseases, orthopaedic conditions
and brain pathology.
Traditionally our Department has focused on clinical imaging research.
However, increasingly we are collaborating with other faculties such as
Engineering and Science, in an effort to develop quantitative imaging
and research into disease biology as it relates to imaging.
Faculty of Medicine Research Report 2003
35
Virtual Spine Workstation - Development of advanced 3D modelling
of the human spinal column using CT and MRI data
Project Description
Principal Investigator
Collaborator
Grants Awarded in 2003
Features of Tumour Aggression in Ductal Carcinoma In Situ of the
Breast: Correlation between in vivo Magnetic Resonance Imaging,
in vitro Magnetic Resonance Spectroscopy, Histology and Gene
Expression Analysis
Principal Investigator
Collaborators
: Assoc Prof Wang Shih-chang
: Mr Philip Iau TC,
Assoc Prof Evelyn Koay,
Dr Manuel Salto-Tellez,
Carolyn Mountford (Sydney Uni IMRR),
Ms Irene Lim (NUH),
Assoc Prof Ong Sim Heng
(Electrical and Computer Engineering)
Evaluation and development of MR urography for evaluation of
paediatric urinary anomalies and dysfunction
Principal Investigator
Collaborators
: Prof Yap Hui Kim
: Dr David Stringer (NUH),
Dr Borys Shuter
Imaging of Articular Cartilage Autografts in the Human Knee MRI of autologous cartilage implants in patients with articular
cartilage ulcers
Principal Investigators
Collaborator
Principal Investigator
Collaborator
: Assoc Prof Wang Shih-chang
: Dr James Hui,
Dr David Stringer (NUH)
Use of 3D multislice CT for the evaluation of ancient
Angkorian skeletons
Principal Investigator
Collaborators
Principal Investigator
Collaborators
Semi-Automated Hippocampal Volumetry in Patients with
Early Dementia
Collaborators
: Dr Borys Shuter
: Yvonne Ho (NUH)
: Assoc Prof Wang Shih-chang
: Dr Sudhakar Venkatesh (NUH),
Assoc Prof Rethy Chhem (Uni Western
Ontario Radiology),
Dr Kyle Latinis,
Ms Wong Kit Mui (NUH)
Optimisation and efficacy of visualisation of pulmonary
thromboembolic disease using multislice CT pulmonary
a ngi ogr a phy
Development of an Asian Bone Age Atlas
Principal Investigator
: Prof Lee Eng Hin,
Dr James Hui
: Assoc Prof Wang Shih-chang
Development of a clinical bowel motility tracer using an
adsorbed radioisotope
Ongoing Projects
Principal Investigator
Collaborators
: Prof Teoh Swee Hin (Mechanical
Engineering)
: Assoc Prof Wang Shih-chang
: Assoc Prof Wang Shih-chang
: Dr Sudhakar Venkatesh (NUH),
Dr Goh Poh Sun,
Ms Wong Kit Mui (NUH)
Advanced 3D Image Reconstruction for Breast MRI - Automated
3D registration of contrast-enhanced breast MRI
: Dr Martha Chiu (Stanford
University Psychology)
: Dr Borys Shuter,
Assoc Prof Wang Shih-chang,
Dr June LM Chong (NUH),
Yeh Ing Berne (NUH)
Principal Investigators
Collaborator
Professor Rethy Chhem cleaning the Pre-Angkonian Skeletal Parts
: Dr Yan Chye Hwang
(Electrical and Computer Engineering),
Mr Tan Ek Tsoon
(Electrical and Computer Engineering)
: Assoc Prof Wang Shih-chang
Electrophoresis of DNA products after PCR amplification
36
Faculty of Medicine Research Report 2003
I Yttrium-90 SIR Sphere Therapy for Unresectable Liver Malignancy
- High dose intra-arterial selective internal radiation therapy for
unresectable liver malignancy. Evaluation of outcomes and
dosimetry methodology
Principal Investigator
Collaborator
: Assoc Proc Wang Shih-Chang
: Dr Borys Shuter
International Publications
Lim EH, Aggarwal A, Agasthian T, Wong PS, Tan C, Sim E, Tan L, Goh PS,
Wang SC, Khoo KL, Mukherjee A, Khoo SM, Chua G, Nilsson B, Lee KH,
Tan P
Feasibility of using low-volume tissue samples for gene expression
profiling of advanced non-small cell lung cancers. Clin Cancer
Res. 2003;9:5980-7.
Ong AW, Isaac JR, Goh PS
Duodenal trauma. J Trauma. 2003;55:802.
Yoon KH, Goh PS
An unusual cause of loin pain in a patient with systemic lupus
erythematosus. J Rheumatol. 2003;30:634-5.
Thamboo T, Tan K, Wang S, Salto-Tellez M
Extra-hepatic embolisation of Y-90 microspheres from selective
internal radiation therapy (SIRT) of the liver. Pathology 2003;
35:351-3.
Salto-Tellez M, Zhang D, Chiu LL, Wang SC, Nilsson B, Koay ES
Immunocytochemistry versus molecular fingerprinting of
metastases. Cytopathology 2003;14:186-90.
Zhang JL, Zhang L, Koh TS, Shuter B
Estimation of renal scintigraphy parameters using a linear
piecewise-continuous model. Phys Med Biol. 2003;48:N167-72.
Friedman L, Finlay K, Popovich T, Chhem RK
Sonographic findings in patients with anterior knee pain. J Clin
Ultrasound. 2003;31:85-97.
Babyn PS, Chu WC, Tsou IY, Wansaicheong GK, Allen U, Bitnun A,
Chee TS, Cheng FW, Chiu MC, Fok TF, Hon EK, Gahunia HK, Kaw GJ,
Khong PL, Leung CW, Li AM, Manson D, Metreweli C, Ng PC, Read S,
Stringer DA
Severe acute respiratory syndrome (SARS): chest radiographic
features in children. Pediatr Radiol. 2004;34:47-58. E-publication
2003, Nov 18.
Wong PS, Leow CK, Goh PS, Chan N
Staff Profile
Inferior vena cava leiomyosarcoma. Eur J Cardiothorac Surg.
2003;23:241.
Goh LA, Chhem RK, Wang SC, Chee T
Iliotibial band thickness: sonographic measurements in
asymptomatic volunteers. J Clin Ultrasound 2003;31:239-44.
Diong, C.H., Lenny K.A. Tan, and C.M.U. Leh
Associate Professor & Head
Professor
Professor (in Bioengineering)
Assistant Professor
Senior Research Scientist
Axial bifurcation in a bicephalic Chelonia mydas embryo. Chelonian
Conservation and Biology: International Journal of Turtle and
Tortoise Research 2003; 4(3): 55-57.
Venkatesh SK, Riederer B, Chhem RK, Cardinal E, Wang SC
Reactivation in post-traumatic chronic osteomyelitis:
ultrasonographic findings. Can Assoc Radiol J 2003;54:163-8.
Wang Shih-chang
Tan Kheng Ann, Lenny
Sheppard, Colin
Goh Poh Sun
Shuter, Borys
Contact Information
Contact Person
Telephone
Email
:
:
:
Ms Koh Wai Leng
6772-4210
dnrsec@nus.edu.sg
Contact Person
Telephone
Email
Facsimile
:
:
:
:
Mdm Cheong May Lee
6772-5207
cheongml@nuh.com.sg
6779-7101
Postal Address
:
Homepage
:
Department of Diagnostic
Radiology
National University Hospital
5 Lower Kent Ridge Road
Singapore 119074
http://www.med.nus.edu.sg/
diagrad/
Using multi-detector CT to aquire high resolution scans of the
Pre-Angkorian Skeleton
Faculty of Medicine Research Report 2003
:
:
:
:
:
37
SUMMARY
DEPARTMENT OF
Medicine
Year 2003 has been a particularly difficult one for the Department
of Medicine as we were directly impacted by the outbreak of SARS
in many ways. Academic staff in the Department with clinical duties
was actively involved in clinical care during the outbreak. Teaching
and research activities were severely curtailed as staff movement was
severely constrained.
Nevertheless, the Department persevered and managed to do some
epidemiological work on SARS even while our infectious disease physicians
seized the opportunity to contribute to medical knowledge on this novel
coronavirus in print. The sero-epidemiological study saw success in both
publication as well as modest external funding, albeit retrospectively.
We even managed to innovate in the area of clinical teaching sans
patients. Another impact of this viral outbreak was the effect on the
economy and funding streams. The Department had enjoyed success in
competitive funding but given the relative paucity of funds, we were still
able to garner A*STAR funding of just under $500,000 for collaborative
GI cancer work. Industry partnerships continued apace but many of our
research groups have found that continued work will be hampered by
lack of funding.
Output has remained healthy despite the modest number of fulltime
academic and research staff, especially given the added load of clinical
work and intensive clinical teaching. These being issues that few of our
sister faculties have had to grapple with.
38
Faculty of Medicine Research Report 2003
Project Description
Grants Awarded in 2003
Comparison of expression of nitric oxide synthase and
cystathionine gamma-lyase genes in human internal thoracic
arteries from normotensive and hypertensive patients
Principal Investigator
Collaborators
: Prof Philip Moore
: Dr GD Webb, (United Kingdom),
Prof Vernon Oh Min Sen,
Dr W. Maung Maung Aye (NUH),
Dr Reida El Oakley (NUH),
Dr Elizabeth A. Taylor,
Dr Shanthi Wasser
A review of drug-related hospital admissions to a general
medicine service
Principal Investigator
Co-Principal Investigators
: Prof Vernon Oh Min Sen
: Ms Josephine Lee (NUH),
Dr Grant Sklar
Host and viral factors contributing to hepatitis B outcomes in a
cohort study
Principal Investigator
: Assoc Prof Lim Seng Gee
Establishment of a Gastric Cancer Epidemiology, Clinical and
Genetics Programme (GCEP) for population-based studies to
identify clinical, serologic, pathological and genetic markers which
can be used to define an optimal approach to gastric
cancer screening
Principal Investigator
Co-Principal Investigator
The role of gastric mucosal cyclo-oxygenase and prostaglandin
in the pathogenesis of gastroduodenitis and ulcer disease in
uremic patients
Principal Investigator
: Assoc Prof Ho Khek Yu
Development of the Transplantation Medical Research Center at
NUS/NUH: Therapeutic Applications in Hematological Malignancies
and Solid Tumours with Non-Myeloablative Transplantation (NMT)
Principal Investigator
Collaborators
: Assoc Prof Chen Chien-Shing
: Dr Lim Hong Liang (NUH),
Dr Tan Lip Kun (NUH),
Dr Tan Poh Lin (NUH),
Dr Liu Te Chih (NUH)
The effect of combining angiotensin receptor blocker and
ACE-inhibitor on proteinuria in type 2 diabetic patients
with nephropathy
Principal Investigator
Co-Principal Investigators
: Prof Lim Pin
: Dr Florence Tan (NUH),
Dr JJ Mukherjee (NUH)
Effect of transdermal botulinum toxin on sweat secretion in
subjects with hyperhidrosis
Principal Investigator
Co-Principal Investigator
Metabolic characteristics of non-diabetic first degree relatives of
patients with type 2 diabetes mellitus in different ethnic groups
in Singapore
Principal Investigator
Co-Principal Investigator
Collaborators
: Prof Lim Pin
: Dr Florence Tan (NUH)
: Dr Stanly Liew (NUH),
Dr Mary Jean Tan (NUH)
Isolating DNA from serum samples
: Assoc Prof Yeoh Khay Guan
: Assoc Prof Ho Khek Yu
: Dr Einar Wilder-Smith
: Dr Elaine Lim
Ongoing Projects
Raxoxifene HCL or placebo in post-menopausal women at risk
for major cardiovascular events
Principal Investigator
: Assoc Prof Lim Yean Teng
Plasmid isolation from E.coli bacteria
Faculty of Medicine Research Report 2003
39
WISDOM
Principal Investigator
Co-Principal Investigator
Immunological alterations in patients undergoing
HBeAg seroconversion
: Assoc Prof Lim Yean Teng
: Dr Tan Huay Cheem
Principal Investigator
The Clinical Utility of Cardiac Neurohormones in the Diagnosis
of Congestive Heart Failure
Principal Investigators
: Dr Carolyn Lam,
Assoc Prof Ling Lieng His,
Assoc Prof Sunil Sethi,
Assoc Prof Lim Tow Keang
: Prof Vernon Oh Min Sen
: Dr Elizabeth A. Taylor,
Dr Eric PH Yap,
MJ Caulfield
: Assoc Prof Lim Seng Gee
: Dr Desmond Wai (NUH)
Predictors of fibrosis and histological activity index in chronic
hepatitis B
: Assoc Prof Lim Seng Gee
: Dr Desmond Wai (NUH)
: Dr Frank J. Peter
: Assoc Prof Lim Seng Gee
: Dr Frank J. Peter
: Assoc Prof Lim Seng Gee
Cancer Therapeutics Research Group
Principal Investigator
: Assoc Prof Lim Seng Gee
Outcome measures in hepatitis B related liver disease: Health
related Quality of Life and financial burden – the impact of
disease progression and intervention
Principal Investigator
Principal Investigator
Collaborator
Principal Investigator
Collaborator
: Assoc Prof Thai Ah Chuan
Characterization of quasispecies in the genome of Hepatitis B
virus and their relation to disease outcome
Principal Investigator
: Dr Lee Yin Mei
: Assoc Prof Lim Seng Gee
Lack of classic precore and core promoter mutations in patients
undergoing HBeAg seroconversion
The natural history of HBeAg positive versus HBeAg negative
chronic hepatitis B patients
Principal Investigator
Principal Investigator
Collaborator
Principal Investigator
Collaborator
Asian Young Diabetes Study (ASDIAB) study (Novo Nordisk)
Principal Investigator
Natural history of anti-HBe positive patients
Risk factors for mortality in patients with hepatitis B reactivation
Establishment of families of Singaporean Chinese subjects to
identify candidate genes in essential hypertension by genomic
search – ‘The NUSIGHT Study’
Principal Investigator
Co-Principal Investigators
: Assoc Prof Lim Seng Gee
: Prof Wong Eu Li, John
Angiogenesis in Osteosarcoma
Principal Investigator
Collaborators
: Prof Robert Pho
: Dr Ivor Lim,
Dr Phan Toan Thang,
Assoc Prof Kong Hwai Loong
Cardiac neuronehormones in hospitalized breathless patients
Principal Investigator
Collaborators
: Dr Carolyn Lam
: Assoc Prof Ling Lieng His,
Assoc Prof Lim Tow Keang
Development of a hepatitis B database
Principal Investigator
: Assoc Prof Lim Seng Gee
International Publications
Ajay K Kakkar, M Levine, HM Pinedo, R Wolff and Wong JEL
Venous thrombosis in cancer patients : Insights from the
FRONTLINE survey, The Oncologist (2003) 8:381-388.
Brun C, D Suter, C Pauli, P Dunant, H Lochmuller, J Burgunder, D Schumperli
and J Weis
U7snRNAs induce correction of mutated dystrophin pre-mRNA
by exon skipping. Cellular and Molecular Life Sciences, 60 (2003):
557-566.
Examining Histological specimens using a light microscope
40
Faculty of Medicine Research Report 2003
Chen CS, K Seidel, M Boeckh, J Clark, D Madtes, J Wagner, R Witherspoon,
C Anasetti, FR Appelbaum, W Bensinger, HJ Deeg, JE Sanders, R Storbs,
J Wade, M Siadak, MED Flowers and KM Sullivan
Incidence and risk factors for developing pneumonia late after
autologus and allogeneic hematopoietic stem cell transplantation.
Krauss J K, TJ Loher, R Weigel, H H Capelle, S Weber and J, Burgunder
Stimulation of the posteroventral lateral globus pallidus internus
in non-DYT1 generalized dystonia and choreoathetosis: 2-years
follow-up. Journal of Neurosurgery, 98 (2003): 785-792.
Lee CG, J Ren, IS Cheong, KH Ban, LL Ooi, Tan S Yong, A Kan, I Nuchprayoon,
R Jin, K H Lee, M Choti and LA Lee
Chua Ai Ping and K H Lee.
Activated Drotrecogin Alfa For Treatment Of Severe Sepsis in
Singapore. Critical Care and Shock, 6, no.2 (2003):67-74.
Expression of the FAT10 gene is highly upregulated in
hepatocellular carcinoma and other gastrointestinal and
gynecological cancers. Oncogene, 22, no.17 (2003): 2592-2603.
Fisher DA, MH Chew, YT Lim and PA Tambyah
Preventing local transmission of SARS: lessons from Singapore.
Medical Journal of Australia, 178 (2003): 555-8.
Fisher DA, TK Lim, YT Lim, KS Singh and PA Tambyah
A typical presentation of SARS. Lancet (2003); 361(9370):1740.
Hsu SI and WG Conser
Chronic Progression of Tubulointerstitial Damage in Proteinuric
Renal Disease is Mediated by Complement. Activation:
A Therapeutic Role for Complement Activation? Journal of the
American Society of Nephrology, 14 (2003): S186-S191.
(Supplement on Proceedings of the 1st NKF Singapore International
Summit on the Prevention of Renal and Related Diseases).
Habib AG and PA Tambyah
Community acquired Klebsiella pneumoniae central nervous
system infections in adults in Singapore. European Journal of
Clinical Microbiology & Infectious Diseases, 22 (2003): 486-8.
Ho KH and BKC Ong
A community-based study of headache diagnosis and prevalence
in Singapore. Cephalalgia, 1 (2003): 6-13.
Hum A, HL Teoh and EC Lim
Thyrotoxicosis-associated propriopinal myoclonus : video
presentation. European Journal of Neurology (2003), Vol 10, Suppl
1:81
Khoo Ai-Leng, Lai-San Tham, KH Lee and Gek-Kee Lim
Acute Liver Failure with Concurrent Bupropion and Carbimazole
Therapy. Annals of Pharmacotherapy, 37,no.2 (2003): 220-223.
Khoo KL, GS Chua, A Mukhopadhyay and TK Lim
Transbronchial needle aspiration: Initial experience in routine
diagnostic bronchoscopy. Respiratory Medicine (2003): 1200-4.
Lee YM, PA Tambyah, KH Lee, KC Tan and SG Lim
Successful treatment of Xylohypha bantiana brain abscess
mimicking invasive cerebral aspergillosis in a liver transplant
recipient. Journal of Infections (2003), Nov, 47(4):348-51.
Lee YM, CB O’Brien, N Yamashiki, M Behro, D Weppler Tzakis A and
ER Schiff
Preservation injury patterns in liver transplantation is associated
with poor prognosis. Transplant Proceedings (2003); 35(8):
2964-6.
Leong SS, EK Tan, KW Fong, EPV Wilder-Smith, YK Ong, BC Tai. L Chew,
SH Lim, J Wee, KM Lee, KF Foo, P Ang and PT Ang
Randomized double-blind trial of combined modality treatment
with or without Amifostine in unresectable stage III non-small
cell lung cancer. Journal of Clinical Oncology, (2003); 21(9):176774.
Liew CF and JS Cheah
Thyrotoxicosis-induced hyperferritinaemia. Hospital Medicine
(2003):64-114.
Liew CF, ES Seah, KP Yeoh, KO Lee and SD Wise
Lean, non-diabetic Asian Indians have decreased insulin sensitivity
and insulin clearance, and raised leptin compared to Caucasians
and Chinese. International Journal of Obesity (2003), 27:784-9.
Lim E
Headache – It’s more than meets the eye : Orbital lesion
masquerading as SUNCT, Cephalagia (2003) 23(7):58-560.
Lim E, YS Wong, YL Lo and SH Lim
Atypical Brown-Sequard Syndrome after Trauma : Case report
and review of the literature. Clinical Neurology and Neurosurgery
(2003) 105:2 : 143-145.
Lim E and YS Wong
Khoo SM and TK Lim
Prescribing and administration of nebulized bronchodilators: A
prospective audit in a university hospital. Respirology 8 (2003):
205-207.
Faculty of Medicine Research Report 2003
Post-traumatic paroxysmal exertional dystonia : Case report and
review of literature. Parkins Related Disorders (2003), 9:6:
371-373.
41
Lim EC, HL Teoh and YS Wong
Paroxysmal exercise-induced dystonia occurring after trauma :
Video report and literature. European Journal of Neurology (2003),
Vol 10, Supp 1:84.
Millward M, M Boyer, M Lehnert, S Clarke, D Rischin, BC Goh, Wong JEL,
E McNeil and J Bishop
Docetaxel and carboplatin is an active regimen in advanced nonsmall cell lung cancer: a phase II study in Caucasian and Asian
patients. Annals of Oncology (2003), 14:449-4545.
Lim EH, Cheong, RS Lim, TS Wu and HL Kong
Oxaplatin/Fluorouracil/Leucovorin in advanced colorectal
carcinoma : an asian experience. Annals of Pharmacotherapy
(2003), 12:1909-12.
Lim CC, WL Lee, YS Leo, KE Lee, KP Chan, AE Ling, H Oh, AP Auchus, NI
Paton, F Hui and PA Tambyah
Late clinical and magnetic resonance imaging follow up of Nipah
virus infection. Journal of Neurology Neurosurgery and Psychiatry
74 (2003): 131-3.
Lim LG and KY Ho
Gastrooesophageal reflux disease at the turn of millennium.
World Journal of Gastroenterology (2003);9:2135-6.
Lim MC, SM Brooke and RM Sapolsky
gp120 neurotoxicity fails to induce heat shock defences,while
the over expression of hsp70 protects against gp120. Brain
Research Bulletin (2003), 61:183-8.
Lim TK, A Mukhopadhyay, Annie Gough, KL Khoo, SM Khoo, KH Lee and
Gamini Kumarasinghe
Nash RA, R Dansey, J Storek, GE Georges, JD Bowen, LA Holmberg, GH
Kraft, MD Mayes, KT McDonagh, CS Chen, DiPersio J LeMaistreC, S
Pavletic, KM Sullivan, J Sunderhaus, DE Furst and PA McSweeney
Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative
Disorder after High-Dose Immunosuppresive Therapy and
Autologous CD-34 Selected Hematopoietic Stem Cell
Transplantation for Severe Autoimune Diseases. Biological Blood
Marrow Transplant (2003)9:583-91.
Oh VMS and TK Lim
Singapore experience of severe acute respiratory syndrome:
specific clinical problems affecting health workers and the
community. Clinical Medicine (2003), September-October, 3(5):44851.
Ong WY, XR Lu, BKC Ong, LA Horrocks, A A Farooqui and SK Lim
Quinacrine abolishes increases in cytoplasmic phospholipase A2
mRNA levels in the rat hippocampus after kinate-induced neuronal
injury. Experimental Brain Research, 148, 4 (2003): 521-524.
Radojevic V, AM Humm, KM Rosler, T Lauterburg and J Burgunder
Role of clinical judgement in the application of a nucleic acid
amplification test for the rapid diagnosis of pulmonary tuberculosis.
Chest, 124, no.3 (2003): 902-908.
Abnormal trafficking of sarcolemmal proteins in alpha-glucosidase
deficiency. Acta Neuropathologica, 105 (2003): 373-380.
Luo N, LH Chew, KY Fong, DR Koh, SC Ng, K H Yoon, S Vasoo, SC Li and
J Thumboo
ERCP in patients with periampullary diverticulum.
Hepatogastroenterology (2003), May-June 50(51):625-8.
A comparison of the EuroQol-5D and the Health Utilities Index
mark 3 in patients with rheumatic disease. Journal of
Rheumatology, 30, 10 (2003): 2268-2274.
Ramirez SPB, TT Durai and SI Hsu
Luo N, LH Chew, KY Fong, DR Koh, SC Ng, KH Yoon, S Vasoo, SC Li and
Thumboo, J
Rajnakova A, PM Goh, SS Ngoi and SG Lim
Paradigms of public-private partnerships in end-stage renal
disease care: The National Kidney Foundation Singapore. Kidney
International, Supplement 83, 63 (2003): S101-S107.
Validity and reliability of the EQ-5D self-report questionnaire in
English-speaking Asian patients with rheumatic diseases in
Singapore. Quality of Life Research, 12, 1 (2003): 87-92.
Singh K, LY Hsu, JS Villacian, A Habib, D Fisher and PA Tambyah
Luo Nan, CSL Fones, J Thumboo and SC Li
Ramirez SPB, SI Hsu and W McClellan
Factors influencing health-related quality of life of Asians with
anxiety disorders in Singapore. Quality of Life Research (2003).
Taking a public health approach to the prevention of end-stage
renal disease: The NKF Singapore Program. Kidney International,
Supplement 83, 63 (2003):S61-S65.
Severe acute respiratory syndrome lessons from Singapore.
Emerging Infectious Disease (2003), (10):1294-8.
Maracellin, PTT Chang, SG Lim, MJ Tong, W Sievert, ML Shiffman, L
Jeffers, Z Goodman, MS Wulfsohn, S Xiong, J Fry and C L Brosgart
Adefovir dipivoxil for the treatment of hepatitis B e antigenpositive chronic hepatitis B. New England Journal of Medicine,
348, 9 (2003): 808-816.
42
Faculty of Medicine Research Report 2003
Sng JH, AB Ali, SC Lee, D Zahar, JEL Wong, G Cross, V Blake, A Sharif and
PTC Iau
BRCA1 2841/5insA is a recurring mutation with a founder effect
in Singapore Malay women with early onset breast/ovarian cancer.
European Journal of Cancer, 1, (4) (2003): 3
Sng JH, AB Ali, D Zahar, SC Lee, JEL Wong, V Blake, A Sharif, G Cross and
PTC Iau
BRCA1 c.2845insA is a recurring mutation with a founder effect
in Singapore Malay women with early onset breast/ovarian cancer.
Journal of Medical Genetics, 40, (10) (2003): e117.
Tambyah PA, KS Singh, AG Habib, KS Chia and YT Lim
SARS: understanding the coronavirus: accuracy of WHO criteria
was similar in a "non-SARS" hospital in Singapore. British Medical
Journal, 327(2003): 620.
Tambyah PA, AG Habib, TM Ng, H Goh and G Kumarasinghe
Community-acquired methicillin-resistant Staphylococcus aureus
infection in Singapore is usually “healthcare associated”. Infection
Control and Hospital Epidemiology (2003), 24(6):436-8.
Tan EK, Chan LL, Yu GX, Rumpel H, EPV Wilder-Smith and MC Wong
Vascular parkinsonism in moyamoya: microvascular biopsy and
imaging correlates. Annals of Neurology (2003), 54:836-40.
Wilder-Smith EPV and WL, A Chow
Water-immersion wrinkling is due to vasoconstriction. Muscle &
Nerve 2003, 27 (2003): 307-311.
Wilder-Smith EPV and WL, A Chow
Water-immersion and EMLA cause similar digit skin wrinkling
and vasoconstriction. Journal of Microvascular Research (2003),
66:68-72.
Wilder-Smith EPV, S Fook-Chong, SE Chew, A Chow and Y Guo
Vasomotor dysfunction in carpal tunnel syndrome. Muscle &
Nerve, 28, 5 (2003): 582-586.
Wilder-Smith EPV, EK Tan, HY Law, Y Zhao, I Ng and MC Wong
Spinocerebellar taxia type 3 presenting as an L-dopa Responsive
Dystonia Phenotype in a Chinese family. Journal of the Neurological
Sciences, 213 (2003): 25-28.
Wilder-Smith EPV, VK Sharma, YC Chan, BKC Ong, EC Lim, HL Teoh and
J Tan
Incidence of preventable causes of hospital admissions due to
epilepsy : a prospective study in Singapore. European Journal of
Neurology (2003), Vol 10, Suppl 1:21.
Wei C L, HE Khoo, KH Lee and W M Hon
Tan WC, X Xiang, D Qiu, SF Lam, T P Ng and RG Hegde
Enhanced Expression of Heme Oxygenase-1 in Cirrhotic Liver.
Journal of Pathology, 199 (2003):324-334.
Epidemiology of respiratory viruses in patients hospitalised with
near fatal asthma, acute exceberation of asthma or chronic
obstructive pulmonary disease. American Journal of Medicine,
115, 4 (2003):272-277.
Wong JEL, Y Ito, P Correa, KCMJ Peeters, CJH van de Velde and
J Macdonald
Tan YJ, SP Lim, P Ng, PY Goh, SG Lim, YH Tan and W Hng
CD81 engineered with endocytotic signals mediates HCV cell
entry: implications for receptor usage by HCV in vivo. Virology
(2003) ;308 (2):250-69.
Teoh HL, Wilder-Smith EPV, EC Lim and J Tan
Acute motor sensory neuropathy following dengue fever treated
with plasmapheresis after failed immunoglobulin therapy.
European Journal of Neurology (2003), Vol (1), Supp 1:182.
Wai CT, KY Ho and KY Kwok
Esophageal dislodgement of variceal ligator cap due to mismatch
of sizes between the ligator cap and the endoscope. Endoscopy
(2003), 39:151.
Wai CT and KY Ho
Therapeutic Strategies in Gastric Cancer. Journal of Clinical
Oncology, December 1 Suppl, 21 (2003): 267-279.
Wong JEL
Are patients with cancer receiving adequate treatment for
thrombosis. Results from Frontline. Cancer Treatment Reviews,
Vol 29(2) (2003), 11-13.
Zhang X, T Zhu, Y Chen, HC Mertani, KO Lee and PE Lobie
Human growth hormone regulated HOXA1 is a human mammary
epithelial oncogene. Journal of Biological Chemistry, (2003),
278:7580-7590.
Zheng PY, J Hua, HC Ng, KG Yeoh and B Ho
Expression of Lewis blood group antigen in Helicobacter pylori
does not interfere with bacterial adhesion property. World Journal
of Gasteroenterology, 9, no.1 (2003): 122-124.z
Reply to Syn et al. Endoscopy (2003);35:796-7.
Faculty of Medicine Research Report 2003
43
Staff Profile
Associate Professor & Head
Professors
Adjunct Professors
Associate Professors
:
:
:
:
Adjunct Associate Professors
:
Assistant Professors
:
Hon Adjunct Assistant Professor
Research Scientist
Senior Research Fellow
Adjunct Senior Research Fellow
Adjunct Senior Fellows
:
:
:
:
:
Research Fellows
:
Adjunct Research Fellow
:
Adjunct Fellows
:
Contact Information
Ong Kian Chung, Benjamin
Chan Heng Leong
Cheah Jin Seng
Chia Boon Lock
Jean Marc Burgunder
Lee Kok Onn
Lim Pin
Liu Tak Bun, Edison
Oh Min Sen, Vernon
Tan Chorh Chuan
Tan Wan Cheng
Wong Eu Li, John
Joseph Thomas August
Feng Pao Hsii
Yoshiaki Ito
Ho Khek Yu
Kong Hwai Loong
Kueh Yan Koon
Lee Jon Chon, Evan
Lee Kang Hoe
Lim Seng Gee
Lim Tow Keang
Lim Yean Teng
Ling Lieng Hsi
Suri, Rajiv
Tambyah, Paul A
Thai Ah Chuan
Wilder-Smith, Einar
Yeoh Khay Guan
Fong Kok Yong
Gwee Kok Ann
Lobie, Peter
Loong Si Chin
Stephen Wise
Thumboo, Julian
(wef 15 July 2003)
Lam Su Ping, Carolyn
Lee Yin Mei
Lim Hsuen, Elaine
Low Fatt Hoe, Adrian
Thumboo, Julian
(up to 28 Feb 2003)
Lim Gaik Bee
Shanthi Wasser
Steven Hsu I-Hong
Li Baojie
Chew Chin Hin
Suresh Sahadevan
Teoh Kheng Hoe, Gerald
Qiu Diwen
Lim Min Chin
Ng Wee Chit
(up to 30 Sept 2003)
Erle Lim Chuen Hian
Tai E Shyong
Wong Soon Tee
44
Contact Person
:
Telephone
Fascimile
Email
:
:
:
Contact Person
:
Telephone
Fascimile
Email
:
:
:
Postal Address
:
Homepage
:
Faculty of Medicine Research Report 2003
Assoc Prof Benjamin KC Ong
Head of Department
6772-4350
6779-4112
mdcongkc@nus.edu.sg
Assoc Prof Einar Wilder-Smith
Departmental Director
(Research)
6772-4171
6779-4112
mdcwse@nus.edu.sg
Department of Medicine
Lower Kent Ridge Road
Singapore 119074
http;//www.med.nus.edu.sg/
medi/index.htm
SUMMARY
Microbiology is increasingly gaining prominence in our lives. Topical
reference to this scientific discipline is widespread, whether in life
sciences, biotechnology, health or environmental issues, food production
and safety, amongst many others. Much of the progress in Microbiology
has accelerated remarkably with the availability of powerful techniques
in molecular biology, cell biology, genetics and biocomputing. Microbiology
is a vital discipline to the development of Life Sciences in Singapore. As
such, the Department of Microbiology is strongly committed to serve
Singapore's growing needs, by contributing to education, research,
professional services and industry. The major Research Programmes
within the Department are focused on Infectious Diseases and Immunology.
Located within the Department are the WHO Collaborating Centre
for Research and Training in Immunology; Bone Marrow and Cord
Blood Registries; MOH Hepatitis B Testing Quality Assurance Centre;
National Malaria Reference Centre, and the Human Genome Laboratory.
To take advantage of the completion of the sequencing of the
human genome and many microbial genomes, the Department is
concentrating on microbial pathogenesis and on the development of
molecular-based microbial diagnostics and vaccines. We are also
involved in a bioengineering initiative in which bioinformatics and
computation biology are utilized to unravel the interaction between
microbial peptides and the host major histocompatibility antigens. Such
precise biocomputational prediction may generate vaccines and
immunotherapeutic procedures against important infectious diseases
and cancers. The Department is blending powerful tools developed in
the physical and computational sciences into biology to develop cuttingedge capabilities in the Life Sciences.
Faculty of Medicine Research Report 2003
45
DEPARTMENT OF
Microbiology
Gene expression and colonization of lactic acid bacteria in
gastrointestinal tract
Project Description
Principal Investigator
Collaborators
Grants Awarded in 2003
Pathogen Recognition and Signaling by Toll-like Receptors, A
Family of Adjuvant Receptors for the Host Immune System to
Sense Different Types of Pathogens
Principal Investigator
: Dr Lu Jinhua
: Assoc Prof Vincent T.K. Chow
Development of a SARS-associated virus replicon cell line for the
identification of potential therapeutic agents for SARS
Principal Investigator
Collaborators
: Dr Hung Siu Chun
: Assoc Prof Vincent T. K. Chow,
Prof Chan Soh Ha
: Dr Hung Siu Chun
: Assoc Prof Lee Yuan Kun
: Dr Ooi Eng Eong (NEA)
Diversity and molecular characterization of multiple antibiotic
resistance determinants in Vibrio harveyi
Principal Investigator
: Assoc Prof Poh Chit Laa
Degradation of phenolic wastes by Pseudomonas species via the
gentisate pathway:cosmid cloning and genetic organization of
the genes in P25X and P35X
Principal Investigator
Principal Investigator
: Assoc Prof Poh Chit Laa
Role of Tetraspanins (MacTSP and CD9) in Dendritic Cell
Morphology and Functions
: Assoc Prof Mary Ng Mah Lee
Identification of functional domains on three-dimensional
reconstructed flavivirus particles
Principal Investigator
Ongoing Projects
Principal Investigator
Principal Investigator
Collaborator
Structural and functional study of flavivirus attachment domain(s)
and the cellular receptors
Identification of human genomic DNA elements capable of
mediating episome persistence in proliferating human cells
Principal Investigator
Ecology of Legionella in Singapore
: Dr Lu Jinhua
SARS coronavirus spike protein interaction with dendritic cells,
macrophages and lung surfactant proteins A and D
Principal Investigator
Collaborator
: Assoc Prof Lee Yuan Kun
: Prof Jimmy Kwang (TLL),
Assoc Prof Mary Ng Mah Lee,
Dr Lim Chor Kiang
: Assoc Prof Mary Ng Mah Lee
The Human Genome Laboratory for the isolation and
characterization of novel human genes
Principal Investigator
: Assoc Prof Vincent T. K. Chow
: Dr Lu Jinhua
Anti-Malarial Drug Discovery from Natural Product Extracts
Host-bacteria and bacteria-bacteria interactions in the
gastrointestinal tract
Principal Investigator
Collaborator
Principal Investigator
Collaborator
: Assoc Prof Sim Tiow Suan
: Dr Lee May Ann (DMERI)
: Assoc Prof Lee Yuan Kun
: Dr Lu Jinhua
Microbial proteome from Pseudomonas species
West Nile virus-infected Vero cells at 16 hrs post infection. Atomic Force
Microscope image showing virus-induced clumping of cytoskeleton
46
Faculty of Medicine Research Report 2003
Investigation of Microbial Metabolic Pathways Based on
Transcriptional Control of Gene Networks
Principal Investigator
Collaborators
: Assoc Prof Sim Tiow Suan
: Prof Vladimir B Bajic (A*STAR),
Assoc Prof Sanjay Swarup (Dept of
Biological Sciences)
V T K Chow, M C Phoon
Measurement of serum leptin concentrations in university
undergraduates by competitive ELISA reveals correlations with
body mass index and sex. Advances in Physiology Education.
2003 : 27(1-4):70-7.
J J H Chu, and M L Ng
International Publications
Characterization of a 105-kDa plasma membrane associated
glycoprotein that is involved in West Nile virus binding and
infection. Virology, 312 (2003): 458-469.
T Yap and M L Ng
J J H Chu, B G H Choo , J W M Lee and M L Ng
Immunopotentiating properties of lentinan (1–>3)-ß- D-glucan
extracted from culinary-medicinal shiitake mushroom Lentinus
edodes (Berk.) singer (Agaricomycetideae). International Journal
of Medicinal Mushrooms, 5 (2003) : 339-358.
Involvement of actin filaments in the budding of West Nile
(Sarafend) virus. Journal of Medical Virology. 71(2003),
3 :463 - 472.
Bongards C, B S Chew and N Lehming
The TATA-binding protein is not an essential target of the
transcriptional activators Gal4p and Gcn4p in Saccharomyces
cerevisiae. Biochemical Journal, 370 (2003): 141-147.
W Cao, Bobryshev, Y. V., Lord, R. S. A., Oakley, R. E. I.,S H Lee and
Lu, J
Dendritic cells in the arterial wall express C1q: potential
significance in atherogenesis. Cardiovascular Research.
60 (2003) : 175-186.
M Chan and T S Sim
Recombinant Plasmodium falciparum NADP-dependent isocitrate
dehyrdogenase is active and harbours a unique 26 amino acid
tail. Experimental Parasitology, 103 (2003) : 120-126.
H S Chin, J Sim, K I Seah and T S Sim
Deacetoxycephalosporin C synthase isozymes exhibit diverse
catalytic activity and substrate specificity. FEMS Microbiology
Letters, 218, no. 2 (2003): 251-257.
J J H Chu, and M L Ng
The mechanism of cell death during West Nile virus infection is
dependent on the initial infective dose. Journal of General Virology
84 (2003) : 3305-3314.
R J Du and B Ho
Surface localized heat shock protein 20 (HS1V) of Helicobacter
pylori. Helicobacter, 8, no. 4 (2003): 257-267.
Gibson-Kueh, S, P Netto, G H Ngoh-Lim, S F Chang, L L Ho, Q W Qin, F
H C Chua, M L Ng and H W Ferguson
The pathology of systemic iridoviral disease in fish. Journal of
Comparative Pathology, 129 (2003): 111-119.
L L Goh, R Koh, P. Loke, T S Sim
Thermostable malae synthase of S. thermovulgaris, Journal of
industrial Microbial Biotechnology, 30 (2003) : 577 – 581.
L L Goh, P Loke, M Singh and T S Sim
Soluble expression of a functionally active P. falcipain-2 fused to
maltose binding protein in E. coli. Protein Expression and
Purification 32 (2003) : 194 – 201.
Y H Goo, Y C Sohn, D H Kim, S W Kim, M J Kang, D J Jung, E Kwak, N
A Barlev, S L Berger, V T K Chow, R G Roeder, D O Azorsa, P S Meltzer,
P G Suh, E J Song, K J Lee, Y C Lee and J W Lee
Activating signal cointegrator 2 belongs to a novel steady-state
complex that contains a subset of trithorax group proteins.
Molecular and Cellular Biology, 23, no.1 (2003): 140-149.
F C Han, M Gong, H C Ng and B Ho
Identification of H. pylori strain specific DNA sequences between
two clinical isolates from NUD and gastric ulcer by SSH. World
Journal of Gasteroenterology, 9, no.8 (2003): 1747-151.
Microarray analysis of enterovirus-71 infected rhabdomyosarcoma cells
compared with uninfected cells. This facilitates high throughput screening
to identify differentially regulated genes in order to provide insights into
the molecular pathogenesis of EV71 infection
Faculty of Medicine Research Report 2003
47
F C Han, H C Ng and B Ho
M L Ng, S H Tan, E E See, E E Ooi and A E Ling
Stability of randomly amplified polymorphic DNA fingerprinting
in genotyping clinical isolates of Helicobacter pylori. World Journal
of Gasteroenterology, 9, 9 (2003): 2021-2024.
Proliferative growth of SARS coronavirus in Vero E6 cells. Journal
of General Virology. 84 (2003) (Pt 12): 3291-303.
W P Koh, Taylor M B, S K Chew, M C Phoon, K L Kang, V T K Chow
Chlamydia pneumoniae IgG seropositivity and clinical history
of ischemic heart disease in Singapore. Journal of Microbiology
Immunology and Infection. 2003; 36(3):169-74.
Y K Lee, P F Chew, B S Soh and L Y Tham
Enhancing phagocystic activity of hemocytes and disease resistance
in the prawn Penaeus mergciiensis by feeding spirulina platensis.
Journal of Applied Phycology, 15 (2003): 1-9.
Y K Lee, H El-Nezami, C A Haskard, S Gratz, K Y Puong and
S Salminen
Kinetics of adsorption and desorption of aflatoxin B1 on viable
and non-viable bacteria. Journal of Food Protection, 65 (2003):
426-430.
Y K Lee, K Y Puong, A C Ouwehand and S Salminen
Displacement of bacterial pathogens from mucus and CaCo-2
cell surface by lactobacilli. Journal of Medical Microbiology, 52
(2003): 1-6.
C G Li, P M L Ng, Y Zhu, B Ho and J L Ding
Tandem repeats of sushi peptide with enhanced LPS-binding and
–neutralising activities. Protein Engineering, 16 (2003): 629-635.
C S Lim, K P Chan, K T Goh and V T K Chow
Y J Ruan, C L Wei, A E Ling, V B Vega, H Thoreau, S Y Se Thoe, J S Chia,
P Ng, K P Chiu, L Lim, Z Tao, K P Chan, L L E Oon, M M L Ng, Y S Leo,
L F P Ng, E C Ren, L W Stanton, P M Long and E T Liu
Comparative full length genome sequence analysis of 14 SARS
coronavirus isolates and common mutations associated with
putative origins of infection. Lancet, 361 (2003):
1779-1785.
J Sim, E Wong, H S Chin and T S Sim
Conserved structural modules and bonding network in isopenicillin
N synthase related non-haem iron-dependent oxygenases and
oxidases. Journal of Molecular Catalysis B-Enzymatic, 23 (2003):
17-27.
J M Tan, E P Tock, V T K Chow
The novel human MOST-1 (C8orf17) gene exhibits tissue
specific expression, maps to chromosome 8q24.2, and is
overexpressed/amplified in high grade cancers of the breast
and prostate. Molecular Pathology. 2003 : 56 (2):109-15.
S K Tai, O J Tan, V T K Chow, R Jin, J L Jones, P H Tan, A Jayasurya,
B H Bay
Differential expression of metallothionein 1 and 2 isoforms in
breast cancer lines with different invasive potential: identification
of a novel nonsilent metallothionein-1H mutant variant. American
Journal of Pathology 2003; 163(5):2009-19.
J W P Teo, L H Zhang and C L Poh
Hemagglutinim-neuraminidase sequence and phylogenetic
analyses of mumps virus isolates from a vaccinated population
in Singapore. Journal of Medical Virology, 70, 2 (2003): 287-292.
Cloning and characterization of a metalloprotease from Vibrio
harveyi strain AP6. Gene, 303 (2003):147-156.
C S Lim, G Kumarasinghe and V T K Chow
J W P Teo, L H Zhang and C L Poh
Sequence and phylogenetic analysis of SH, G and F genes and
proteins of human respiratory syncytial virus isolates from
Singapore. Acta Virologica, 47, 2 (2003): 97-104.
Cloning and characterization of a novel lipase from Vibrio harveyi
strain AP6. Gene, 312 (2003):181-188.
B L Ng, S H Quak, M M Aw, K T Goh and B Ho
What is True Community-Acquired Urinary Tract Infection?
Comparison of Pathogens Identified in Urine from Routine
Outpatient Specimens and from Community Clinics in a Prospective
Study. European Journal of Clinical Microbiology & Infectious
Diseases, 22 (2003): 242-245.
Immune responses to differentiated forms of Helicobacter pylori
in children with epigastric pain. Clinical and Diagnostic Laboratory
Immunology, 10, no. 5 (2003): 866-869.
M L Ng, S H Tan, E E See, E E Ooi and A E Ling
Early events of SARS coronavirus infection in vero cells. Journal
of Medical Virology. 71(3) (2003) : 323-31.
48
T Y Ti, G Kumarasinghe, M B Taylor, S L Tan, A Ee, C Chua and A Low
L H Wang, B Ho and J L Ding
Transcriptional regulation of a limulus Factor C: repression of an
NFKB motif modulates its responsiveness to bacterial
lipopolysaacharide. Journal of Biological Chemistry, 278 (2003):
49428-49437.
Faculty of Medicine Research Report 2003
T Wagenaar, T, V T K Chow, C Buranathai, P Thawatsupha and C Grose
The out of Africa model of varicella-zoster virus evolution: single
nucleotide polymorphisms and private alleles distinguish Asian
clades from European / North American clades. Vaccine, 21, 1112 (2003): 1072-1081.
Fellow
Senior Tutor
SMF Postdoctoral Fellow
Research Fellow
Research Assistants
:
:
:
:
:
Lim Chor Kiang
Justin Wong Soon Boon
AMA Nasirudeen
Li Jun
Ang Yi Ting, Edlyn
Aw Yong Koh Meng
Koh Kai Shyang
Liu Boping
New Jen Yan
Ng Seok Shin
Raghavan Bhuvanakantham
Zhao Jin
C C Yeo, M V Wong, K P Song and C L Poh
Molecular characterization of an inducible gentisate 1, 2dioxygenase gene, X1nE, from Pseudomonas alcaligenes NCIB
9867. Gene, 312 (2003): 239-248.
H Yoshikawa, M Nagashima, K Morimoto, Y Yamanouti, E H Yap and
M Singh
Freeze-fracture and cytochemical studies on the in vitro cyst form
of reptilian Blastocystis pythoni. Journal of Eukaryotic
Microbiology, 50, no. 1 (2003): 70-75.
Contact Information
Contact Person
Telephone
Email
:
:
:
Ms Ong Shiao Ling
6874-3652
micosl@nus.edu.sg
Contact Person
Telephone
Email
:
:
:
Ms Geetha Baskaran
6874-3275
micgb@nus.edu.sg
Sequence and structural diversity in endotoxin-binding
dodecapepeptides. Biochimica et Biophysica Acta, 1611 (2003):
234-242.
Contact Person
Telephone
Email
:
:
:
Ms Siti Masnor
6874-7891
micsmm@nus.edu.sg
P Y Zheng, J Hua, H C Ng, K G Yeoh and B Ho
Contact Person
Telephone
Email
:
:
:
Kok Chun Yew
6874-3276
mickcy@nus.edu.sg
Postal Address
:
Facsimile
Homepage
:
:
Department of Microbiology
Faculty of Medicine
National University of
Singapore, 5 Science Drive 2
Singapore 117597
6776-6872
http://www.med.nus.edu.sg
/mbio
H X Yu, E C Ren and S H Chan
Associations of HLA microsatellites with rheumatoid arthritis in
Singaporean Chinese. Tissue Antigens, 62 (2003): 133-138.
Y Zhu, B Ho and J L Ding
Expression of Lewis blood group antigen in Helicobacter pylori
does not interfere with bacterial adhesion property. World Journal
of Gasteroenterology, 9, no.1 (2003): 122-124.
Staff Profile
Associate Professor & Head
Professor
Associate Professors
:
:
:
Associate Professorial Fellows
:
Assistant Professors
:
Vincent Chow Tak Kwong
Chan Soh Ha
Yap Eu Hian
Mary Ng Mah Lee
Ho Bow
Lee Yuan Kun
Sim Tiow Suan
Poh Chit Laa
Ren Ee Chee
Tan Hai Meng
Mulkit Singh
Nga Been Hen
Song Keang Peng
Mark Taylor
Seah Geok Teng
Norbert Lehming
Eugene Hung Siu Chun
Kevin Tan Shyong Wei
Wong Siew Heng
Lu Jinhua
Faculty of Medicine Research Report 2003
49
SUMMARY
DEPARTMENT OF
Obstetrics &
Gynaecology
The main goal of our research programs in the next few years is to set
the stage for the Department to regain its international role as the
pioneer of the most important clinical advances in the care of women.
To this end, we have reorganized our research efforts to stay focused
and yet be sufficiently broad to encompass new staff that will be recruited
and new research opportunities that may arise in the future.
The four strategic areas of focus are:
1. Cell-based Therapies including embryology,
2. Drug discovery / Reproductive Pharmacology and Early Phase
Clinical Trials,
3. Reproductive Cancer Biology, Genomics, Proteomics and
4. Mechanisms of Reproductive Diseases.
The cell-based therapies group continue to build on its successes with
high impact publications and its leader Prof Bongso has taken a leading
part in organizing the International Stem Cell Conference in Singapore
in 2003. This international meeting comprised 500 leading researchers
from around the globe and was aimed at encouraging interaction between
local and international stem cell scientists. The NUS-Johns Hopkins
Consortium on herbal drug development lead by Assoc Prof E.L. Yong
has secured a planning grant from US NIH for the development of an
international center for herbal research in Singapore. Dr Loy Chong Jin
and Dr Gong Yin Han from this group have won the Young Scientist of
the Year and Best Clinical Science poster prizes respectively at the 7th
NUH/NUS ASM. They have published several seminal papers including
one in the prestigious Proceedings of the National Academy of Sciences,
USA. Dr Chong Yap Seng from the Mechanism of Disease group has
secured funding from multidisciplinary group with Swedish investigators
to study the influence of maternal diet on breast milk content and
development in offspring.
50
Faculty of Medicine Research Report 2003
Project Description
Grants Awarded in 2003
A survey on the Prevalence of Menstrual Disorder in Adolescent
Girls in Singapore
Principal Investigator
Collaborator
: Dr Annapoorna Venkat
: Assoc Prof Joe Max Mongelli
The influence of Maternal Ethnic Group and Diet on Breast Milk
Fatty Acid Content
Principal Investigator
Collaborators
: Dr Chong Yap Seng
: Dr Chng Seo Yi,
Prof Birgitta Strandvik,
Em Prof LarsAke Hanson,
Dr Marina Korotkova,
Dr Gong Yinnah,
Dr Mabel Deurenberg Yap,
Prof Hugo Van Bever
Antenatal Preparation of Postnatal Counselling - a Randomised
Controlled Trial to Compare Strategies for Improving
Breastfeeding Rates
Principal Investigator
Collaborators
: Assoc Prof Mary Rauff
: Ms Chan Yah Shih,
Dr Chong Yap Seng,
Dr Su Lin Lin,
Dr Chang Yiong Huak
NUH Clinical Research Database for Gynaecologic Oncology
Principal Investigator
: Dr Khalil Razvi
Pre-clinical studies using hormone-responsive bioassays as
surrogate biomarkers to measure selective estrogen receptor
modulator (SERM) activity in serum following oral administration
of flavonoid-enriched traditional Chinese herbal extracts
Principal Investigator
Collaborators
Screening and characterization of photo-flavonoids and defined
traditional Chinese herbal extracts for anti-SARS coronavirus
activity and their use as therapeutic agents
Principal Investigator
Collaborators
: Assoc Prof Yong Eu Leong
: Dr Ooi Eng Wong,
Dr Loh Yin Sze,
Dr Gong Yin Han,
Ms Shen Ping
Transcriptome Analyses of Human Embryonic Stem Cells
Using SAGE
Principal Investigator
Collaborator
: Prof Ariff Bongso
: Dr Chan Woon Khiong
Use of 3D ultrasound scans to optimise successful embryo transfer
in IVF
Principal Investigator
Collaborators
: Dr Foong Lien Cheun
: Assoc Prof Jothi Kumar,
Assoc Prof Arijit Biswas
Rapid diagnosis of common chromosomal aneuploidies
(chromosomes 13, 18, 21, X and Y) using quantitative fluorescent
polymerase chain reaction
Principal Investigator
: Dr Mahesh Choolani
Perinatal Exposure to Organochlorine Pesticides and
Polychlorinated Biphenyls in Singapore
Principal Investigator
Collaborators
Excellence for Singapore Award, May 2003
: Assoc Prof Yong Eu Leong
: Ms Shen Ping,
Dr Gong Yin Han
: Assoc Prof Joe Max Mongelli
: Assoc Prof J Obbard,
Dr A Loganath
Prof Ariff Bongso receiving the Fellowship (ad eundem) of the Royal College
of Obstetricians & Gynaecologists, September 2003
Faculty of Medicine Research Report 2003
51
Johns Hopkins University-National University of Singapore Center
for Research on Complementary and Alternative Medicine
(Planning Grant) (PICRC). United States National Institutes of
Health, National Center for Complementary and Alternative
Medicine (NIH-NCCAM)
Sonographic changes in bone and biochemical markers of bone
turnover during pregnancy and puerperium
Principal Investigator
Collaborators
Identification of Uterine-specific Estrogen Responsive Genes
involved in the pathogenesis of uterine fibroids
: Assoc Prof Yong Eu Leong
: Prof Ong Choon Nam,
Dr Hong Yan (Temasek Life Sciences),
Dr Goh Boon Cher (NUH),
Dr Ronan Kelly,
Dr Steven Wise (Eli Lilly –NUS)
Ongoing Projects
Spatial and temporal patterns of hormone disrupters in Singapore's
marine environment: Molecular Cellular and human effects
Principal Investigator
Collaborators
: Assoc Prof Yong Eu Leong
: Ms Elissa Lim Lis Sa,
Dr Loy Chong Jin,
Assoc Prof Chan Eng Soon,
Dr Elizabeth Taylor,
Assoc Prof Jeffery Obbard,
Dr Simon Pehkonen
Principal Investigator
Collaborator
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Dr Stephen Chew Siong Lin
: Assoc Prof Joe Max Mongelli
: Dr Su Lin Lin
: Assoc Prof Arijit Biswas,
Dr K Vanaja
: Ms Chan Yah Shih
: Dr Citra N Mattar,
Dr Chong Yap Seng,
Assoc Prof Mary Rauff
: Dr Chong Yap Seng
: Dr Samuel Chong,
Assoc Prof Arijit Biswas,
Dr Heng Chew Kiat,
Dr Caroline Lee
The effect of early nutrition on infant adiposity – a prospective
cohort study
Principal Investigator
Collaborators
: Assoc Prof Mary Rauff
: Dr Steven Ng Chin Yuen,
Dr Chong Yap Seng,
Dr Citra N Mattar
Dr Stephen Chew,
Dr Mabel Deurenberg-Yap,
Assoc Prof Paul R M Deurenberg
The efficacy of low dose misoprostol vaginal pessaries for cervical
priming – a randomized controlled trial
Development of a First Trimester Screening Program for
Chromosomal Anomalies in Asian Pregnancies
Principal Investigator
Collaborator
: Dr Loy Chong Jin
: Assoc Prof Yong Eu Leong
The use of misoprostol versus intra-amniotic prostaglandins
for mid-trimester termination of pregnancy – a randomised
controlled trial
The effects of antenatal breast preparation on the
successful initiation and continuation of breast-feeding in
Singaporean mothers
Principal Investigator
Collaborators
: Assoc Prof Joe Max Mongelli
: Dr A Loganath
Genetic epidemiology of preeclampsia
Development of second-trimester ultrasound dating formulae for
Asian pregnancies
Principal Investigator
Collaborator
Principal Investigator
Collaborator
Principal Investigator
Collaborators
: Assoc Prof Joe Max Mongelli
: Prof Victor Goh
: Dr Chua Tsei Meng
: Dr Tan Thiam Chye,
Dr Chong Yap Seng,
Assoc Prof Mary Rauff,
Assoc Prof Arijit Biswas
Molecular Mechanisms of Synergistic Action, and Clinical
Effectiveness of compounds from the herb, sx, on androgen and
estrogen-receptor function
Principal Investigator
Collaborator
: Assoc Prof Yong Eu Leong
: Assoc Prof Paul Heng Wan Sia
(Dept of Pharmacy)
Poor response to ovarian stimulation with follicle-stimulating
hormone: possible genetic causes
Principal Investigator
Collaborator
: Assoc Prof Ashim C. Roy
: Prof Ng Soon Chye
Organizers of the Minisymposium on Herbs and Human Health: Ancient
Cures, Modern Science
52
Faculty of Medicine Research Report 2003
Functional Significance of Fas-FasL Pathway of Apoptosis in
Normal and Malignant Trophhoblasts
Principal Investigator
Collaborators
: Assoc Prof Joe Max Mongelli
: Dr A Loganath,
Mr Gangaraju Raja Shekhar
Clinical application of 22-1-1 monoclonal antibody:
Immunohistochemical detection of 22-1-1 antigen in
gynaecological cancer specimens and its value in clinical
management of such patients
Principal Investigator
Collaborators
Feeder Free Growth of ES Cells or use of Human Feeder Cells
Principal Investigator
Collaborator
: Prof Ariff Bongso
: Mr Robert Klupacs (ES Cell International)
To study the association between fibrinolytic and inhibitor level
in maternal and fetal circulation and pregnancy outcome in
preeclampsia in Medan, Indonesia
Principal Investigator
Collaborators
: Mr Stephen Koh
: Dr Thamrin Tanjung
(University of North Sumatra),
Prof Djaffar Siddik
(University of North Sumatra),
Assoc Prof PC Wong
Development of autologous corporal tissue for male
erectile dysfunction
Principal Investigator
Collaborators
: Assoc Prof P Ganesan Adaikan
: Dr Dietmar W Hutmacher,
Assoc Prof Hanry Yu
Mechanism, pathophysiology and possible treatment options for
female sexual disorders
Principal Investigator
Collaborators
: Assoc Prof P Ganesan Adaikan
: Prof Ng Soon Chye,
Dr Srilatha Balasubramanian
Molecular Abnormalities of Luteinizing Hormone And Their
Clinical Effects
Principal Investigator
Collaborators
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Dr Foong Lian Cheun
: Dr Vanaja K,
Dr Chong Yap Seng
Diagnosis of fetal growth retardation using 3- dimensional
assessment of fetal liver volumes
Principal Investigator
Collaborators
: Dr M Choolani
: Assoc Prof Arijit Biswas,
Assoc Prof Ananda,
Assoc Prof Wong Yee Chee
Principal Investigator
Collaborators
: Prof Kuldip Singh
: Dr Fong Yoke Fai,
Assoc Prof AC Roy,
Dr WX Liao,
Mr Stephen Koh,
Dr Lindoff Claes,
Assoc Prof Bertil Casslen
Estrogen receptor subtypes in the growth of uterine leiomyomas
Principal Investigator
Collaborators
: Assoc Prof Yong Eu Leong
: Dr Bhagavath,
Mr Lim Sai Kiang,
Prof Ng Soon Chye
To evaluate the efficacy and safety of vaginal misoprostol in
terminating early first trimester unwanted pregnancy
Principal Investigator
Collaborator
: Prof Kuldip Singh
: Dr Fong Yoke Fai
Characterization And Cloning of Transcription Cofactors Regulating
Androgen Receptor Function (renewal)
Principal Investigator
Collaborators
Faculty of Medicine Research Report 2003
: Dr Fong Yoke Fa
: Assoc Prof Kuldip Singh,
Dr WX Liao,
Assoc Prof AC Roy,
Assoc Prof KO Lee
Use of the Levonogestrel-releasing Intrauterine System in the
Treatment of Menorrhagia: Influence on MRNA and Antigen
Expression of Plasminogen Activator Inhibitors in the Endometrium
: Assoc Prof Arijit Biswas
: Assoc Prof A C Roy
Studies of the changes in peripheral vascular reactivity and skin
blood flow in normal and abnormal pregnancy
: Assoc Prof A C Roy
: Dr Liao W X,
Prof Ng Soon Chye
A novel regimen to achieve Amenorrhoea using the levonorgestrelreleasing intrauterine system for combined hormone replacement
therapy in premenopausal women and its correlation with MRNA
expression of IGF-1, IGF-II and IGFBP-1 in the endometrium
Effect of Norplant subdermal contraceptive implants on lipid
metabolism – A randomised controlled study
Principal Investigator
Collaborator
: Assoc Prof Tham KF
: Dr Kenzo Sonoda,
Dr Khalil Razvi,
Prof Lee YS,
Assoc Prof Lim Fang Kan,
Assoc Prof Yong Eu Leong
53
: Assoc Prof Yong Eu Leong
: Assoc Prof Jenster Guido,
Mr F John Ghadessy,
Prof Ng Soon Chye
Effect of the Levonorgestrel Releasing Intrauterine System (LNGIUS) on Lipid Metabolism - A Randomised Controlled Study
Principal Investigator
Collaborators
: Prof Kuldip Singh
: Dr Fong Yoke Fai,
Assoc Prof AC Roy
Efficacy and safety of Growth Hormone Augmentation Therapy
in Men and Women with Low GH
Principal Investigator
Collaborators
: Prof Victor Goh Hng Hang
: Dr Oei Pau Ling,
Prof Ng Soon Chye
Principal Investigator
Collaborators
: Prof Victor Goh Hng Hang
: Mr Chan Poh Chong,
Assoc Prof A Biswas,
Ms Tain CF
Principal Investigator
Collaborators
Principal Investigator
Collaborators
Principal Investigator
Collaborator
: Prof Ariff Bongso
: Dr Fong Chui Yee
Differential Gene Expressions in the Placentae in Singleton
and Multiple Pregnancies with or without Intrauterine
Growth Retardation
Principal Investigator
Collaborators
: Prof Ng Soon Chye
: Dr Nguyen BX,
Dr Liao Swee Lian,
Prof Edmund Lee,
Dr S Moochhala
Comprehensive evaluation of the effects of oestrogen in male
reproductive health and disease
: Dr Leena A Gole
: Dr Annapoorna V,
Mdm Sun Xiaoli
Propagation and application of human embryonic stem cells for
tissue engineering
Principal Investigator
Collaborator
: Prof Victor Goh Hng Hang
: Prof Ng Soon Chye,
Dr Oei Pau Ling
Cellular and Nuclear Reprogramming
: Prof RNV Prasad
: Mr Stephen Koh,
Dr Vanaja K,
Prof Ng Soon Chye
Detection of Low Grade Mosaicism in Turner's Syndrome Using
Fluorescence in situ Hybridization (FISH)
Principal Investigator
Collaborators
: Assoc Prof Wong Yee Chee
: Dr A Loganath,
Mr G Raja Shekhar
The social, behavioural, cognitive, physiological, biochemical,
nutritional and endocrine determinants of the process of ageing
in men and women in Singapore: Identifying basis for supplements,
augmentation therapies, and lifestyle modification so as to delay
the process of ageing and reduce the risk of age-related illnesses
Changes in the Coagulation and Fibrinolytic Levels during the
Menstrual Cycle and in Patients with Menorrhagia
Principal Investigator
Collaborators
: Assoc Prof A C Roy
: Dr WX Liao,
Assoc Prof Joe Max Mongelli,
Prof Ng Soon Chye
Interaction between placental cell adhesion molecules and
angiogenic factors in normal pregnancy, pre-eclampsia and fetal
growth restriction
Principal Investigator
Collaborators
An Animal Model To Evaluate The Feasibility And To Optimise The
Conditions For In Utero Cord Blood Stem Cell Transplantation
Using An Inbred Guinea Pig Strain
Principal Investigator
Collaborators
Mitochondrial DNA Mutations and Gestational Diabetes Mellitus
: Assoc Prof P Ganesan Adaikan
: Prof Ng Soon Chye
To Examine Appropriate Methods of Genetic Analysis In Mature
Human Spermatozoa And For Rapid Prenatal Diagnosis In Samples
Obtained By Specific Non-Invasive And Invasive Methods
Principal Investigator
Collaborators
: Assoc Prof Arijit Biswas
: Dr Nuruddin B Mohd,
Dr Chan Woon Kiong
Automated Micro-manipulation for Nuclear Reprogramming
: Assoc Prof Clement Chan
: Mr S Charnocks Jones,
Assoc Prof AC Roy,
Prof Ng Soon Chye
Principal Investigator
Collaborator
: Prof Ng Soon Chye
: Assoc Prof Tan Kok Kiong (Department
of Electrical Engineering)
Potential Release of Slow Release Progestin Systems for Long
Term Treatment of Pelvic Pain Secondary To Endometriosis
Non invasive prenatal diagnosis using fetal erythroblasts derived
from first trimester maternal blood
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Dr Fong Yoke Fai
: Prof Kuldip Singh,
Dr FH Loh
54
: Dr Mahesh A Choolani
: Assoc Prof Arijit Biswas,
Assoc Prof AC Roy
Faculty of Medicine Research Report 2003
Genetic variability of estrogen receptor genes and human
reproductive disorders
MA Choolani, KO' Donoghue, S Kumar D Talbert, I Roberts, PR Bennett
and NM FIsk
Principal Investigator
Collaborators
Characterisation of primitive fetal erythroblasts for first trimester
non-invasive prenatal diagnosis using fetal cells derived from
maternal blood. Molecular Human Reproduction, 9,4 (2003) :
227-35.
: Assoc Prof AC Roy
: Prof Ng Soon Chye,
Dr Liao WX
A comparative study on the effect of a calcium-fortified drink
(Pink Dolphin-Calcium), and calcium carbonate tablets on bone
density in a population of adult Singaporean women who have
osteopenia either at the spine or hip
Principal Investigator
Collaborators
: Prof Victor Goh Hng Hang
: Dr Oei Pau Ling,
Dr Wong MT
International Publications
GS Condous, S Arulkumaran, I Symonds, R Chapman, A Sinha and
R Khalil
The Tamponade Test in the Management of Massive Postpartum
Hemorrhage. Obstetrics and Gynecology, 101 (2003): 767-772.
Y Gong , HS Chin, LS Lim, JS P Obbard and EL Yong
Clustering of Sex Hormone Disruptors in Singapore's Marine
Environment. Environmental Health Perspectives, 11 (2003) :
1448- 1453.
SS Ho, KO' Donoghue, M Choolani
PG Adaikan and B Srilatha
Oestrogen-mediated hormonal imbalance precipitates erectile
dysfunction. International Journal of Impotence Research, 15
(2003) : 38-43.
Fetal cells in maternal blood: state of the art for non-invasive
prenatal diagnosis. Ann Acad Med Singapore 2003;32:597-603;
quiz 604.
CJ Loy, KS Sim and EL Yong
A Adebiyi, PG Adaikan and RNV Prasad
Tocolytic and toxic activity of papaya seed extract on isolated
rat uterus. Life Sciences, 74, 5 (2003): 581-592.
Filamin-A localizes to the nucleus to regulate androgen receptor
and coactivator functions. Proceedings of the National Academy
of Sciences of the United States of America, 100 N(2003): 45624567.
A Biswas
Management of previous cesarean section. Current Opinion
in Obstetrics and Gynaecology, 15,2 (2003) : 123-129 .
KO’ Donoghue, M Choolani, J Chan, de la Fuente J, S Kumar, C Campagnoli,
PR Bennett, IAG Roberts, NM Fisk
A Biswas, OAC Viegas and AC Roy
Identification of fetal mesenchymal stem cells in maternal blood:
implications for non-invasive prenatal diagnosis and feto-maternal
microchimaerism. Mol Hum Reprod 2003; 9:497-502.
Effect of Implanon and Norplant subdermal contraceptive implants
on serum lipids- A randomised comparative study. Contraception,
68,3 (2003): 189-193. (Original article, Randomized
Controlled Trial).
N Chen, WY Yip, LG Tan, SL Liow and SC Ng
Influence of Multiple Electrical Pulses on Parthenogenetic activation
and Subsequent in-vitro development of mouse oocytes.
Theriogenology, 59,1 (2003): 472.
R Casella, , MR Maduro, A Mifsud, LI Lipshultz, EL Yong and DJ Lamb
Androgen Receptors Gene Polyglutamine Length is Associated
With Testicular Histology in Infertile Patients. Journal of Urology,
169 (2003) : 224-227.
M Choolani, J Chew, AEJ Yeoh , AE Kg
Modern Medicine: To Share, To Educate, To Investigate. Editorial.
Ann Acad Med Singapore 2003;32 (Suppl):S1.
Faculty of Medicine Research Report 2003
Probst-Hensch, NM Fisk, H Wang, VHH Goh, ALH Seow, HP Lee and
MC Yu
Determinants of circulating insulin-like growth factor I and insulin
liked growth factor binding protein 3 concentrations in a cohort
of Singapore men and women. Cancer Epidemiology Biomarkers
& Prevention, 12 (2003): 739-746.
G Rajashekhar, A Loganath, AC Roy and YC Wong
Over-expression and Secretion of Angiogenin in Intrauterine
growth retardation Placenta. Molecular Reproduction and
Development, 64, (2003):397-404.
S Ranggapa, F Chen, EH Lee, TA Bongso and EKW Sim
Transformation of adult mesenchymal stem cells isolated from
the fatty tissue into cardiomyocytes. Annals of Thoracic Surgery,
75 (2003): 775-779.
55
M Richards, S Tan, CY Fong, A Biswas, WK Chan and TA Bongso
Research Fellows
:
Adjunct Researcher
Research Assistants
:
:
Tain Chee Fei
Leena A Gole
Alexis Heng Boon Chin
Chen Naiqing
Liow Swee Lian
Terry Tong
Joyce P I Lim
Srilatha Balasubramanian
Fong Chui Yee
Kalamegam Gauthaman
Huang Sunan
Shen Ping
Ponnusamy Sukumar
Gideon Khoo
Joyce Elizabeth Mathew
Lau Lang Chu
Rajeev Kumar Sukumaran
Gangaraju Raja Shekhar
Loy Chong Jin
Sim Kim Siew
Mark Richards
Manickam Arunkumar
Shawna Tan Ai Lin
Tan Hwee Hwee
Nee Mary
Ng Boon Leong, Robin
Comparative evaluation of various feeders for prolonged
undifferentiated growth of human embryonic stem cells. 21, 5
(2003): 546-556.
BA Roopa, A Loganath and K Singh
The effect of a levonorgestrel-releasing intrauterine system on
angiogenic growth factors in the endometrium. Human
Reproduction, 18,9 (2003): 1809-1819.
K Singh, YF Fong, and F Song
A viable alternative to surgical vacuum aspiration: repeated doses
of intravaginal misoprostol over 9 hours for medical termination
of pregnancies up to eight weeks. British Journal of Obstetrics
& Gynaecology, 110, 2 (2003); 175-180.
KK Tan, S Huang, TH Lee and SY Lim
A discrete-time iterative learning algorithm for linear time-varying
systems. Engineering Applications of Artificial Intelligence, 16, 3
(2003): 185-190.
EL Yong, CJ Loy and KS Sim
Androgen receptor gene and male infertility. Human Reproduction
Update, 9 (2003): 1-7.
Contact Information
Staff Profile
Associate Professor & Head
Professors
:
:
Associate Professors
:
Assistant Professors
:
Senior Lecturers
:
Research Professors
:
Research Associate Professors
:
Senior Research Fellow
:
P C Wong
Ng Soon Chye
R N V Prasad
Kuldip Singh
Wong Yee Chee
Mary Rauff
A Ilancheran
Jothi Kumar
Yong Eu Leong
Lim Fang Kan
Joe Max Mongelli
A Biswas
Mahesh A Choolani
Khalil Razvi
Oei Pau Ling
Chong Yap Seng
Fong Yoke Fai
Stephen Chew Siong Lin
Foong Lian Cheun
Ariff Bongso
Victor Goh Hng Hang
A C Roy
P Ganesan Adaikan
Loganath Annamalai
56
Contact Person
:
Telephone
Facsimile
Email
Postal Address
:
:
:
:
Homepage
:
Faculty of Medicine Research Report 2003
Assoc Prof P C Wong
Head of Department
6772-4261
6779-4753
obgsec@nus.edu.sg
Department of Obstetrics
& Gynaecology
Faculty of Medicine
National University of
Singapore
Singapore 119260
http://www.obgyn.nus.edu.sg
INTRODUCTION
Research efforts in the Department of Ophthalmology remain closely
integrated with the Singapore Eye Research Institute (SERI), an NUS
affiliated national research institute, as all NUS Dept of Ophthalmology
staff currently play leading roles in the direction of SERI, the national
coordinating body for ophthalmic and vision research in Singapore. The
Department’s research efforts have also been augmented with the
opportunities for close interaction with affiliated SERI participants, which
include eye departments from both medical clusters, the Defence Medical
Research Institute (DMRI) and the Optometry Centre of the Singapore
Polytechnic. This report focuses on specific research achievements by
NUS Department of Ophthalmology staff in 2003.
SUMMARY OF RESEARCH ACHIEVEMENTS IN 2003
In 2003, Department staff were successful in securing 9 new research
grants and continued to support 25 ongoing research projects. In general,
research in 2003 continued to focus on major eye diseases of specific
relevance to our region, and included projects in myopia, ocular surface
stem cells, retinal vascular disorders, cataract surgery, ocular infections
and glaucoma. Department staff also published a total of 51 scientific
papers in peer reviewed international journals with a mean impact factor
of 2.601.
RESEARCH HIGHLIGHTS IN 2003
1. First Combined Meeting between SERI and the Association for Research
in Vision and Ophthalmology (ARVO)
The Department actively participated in a major research meeting event
in February 2003 - the First Combined Meeting between SERI, and the
Association for Research in Vision and Ophthalmology (ARVO). ARVO
is the leading forum for ophthalmic research in the world, and until
now, has always been held only in the US. Deemed a great success,
the SERI-ARVO meeting was the first such meeting to be held outside
the USA, with more than 800 delegates from 36 countries who attended.
Dept staff were integral in the planning and conduct of the meeting,
and ran a series of oversubscribed teaching workshops in ophthalmic
research methodologies.
2. Ocular Surface Stem Cell Transplantation Program
Our ocular surface stem cell program has been successful in performing
the first few cultured conjunctival stem cell transplants. In 2003, over
20 transplants have been performed with good success, and 3 out of 4
manuscripts have been accepted, or are in press, slated for publication
in 2004. These include 2 papers on new serum-free culture methods in
Investigative Ophthalmology and Visual Science (IOVS), and Current Eye
Research, and 1 clinical paper on cultured conjunctival stem cell
transplantation in Transplantation.
Faculty of Medicine Research Report 2003
57
DEPARTMENT OF
Ophthalmology
3. Completion of active phase of ATOM RCT
We have completed 2 year follow-up of all 400 patients in this major
RCT on the use of atropine eyedrops in retarding myopia progression in
schoolchildren. Results are spectacular, with atropine shown to be highly
effective in retarding myopia progression and eyeball elongation, and
also having a good safety profile. This study was highlighted at the 2003
ARVO meeting in Florida, and a manuscript has been submitted to the
New England Journal of Ophthalmology. ATOM is now in its final stage
of 3rd year observational follow-up, and a new RCT is being planned to
evaluate bilateral treatment in children and reduced therapeutic
concentrations of atropine.
DEPARTMENT OF
Ophthalmology
4. New Pilot Clinical Trial on NeuroVision Technology
NeuroVision Correction Technology (NVT) is a novel interactive computerbased visual enhancement program based on sound neural science and
visual psychophysics principles which has shown to improve visual acuity
and contrast sensitivity in adult amblyopia in a FDA RCT. We embarked
on a pilot study in collaboration with DMRI to evaluate the use of NVT
in improving vision in individuals with low myopia not exceeding –1.5D.
Results are extremely encouraging, with 80% of individuals showing
improvement in unaided visual acuity, and a major RCT is planned in
collaboration with DMRI and the SAF. Further studies on amblyopia and
pediatric myopia are planned. Funded by EDBI and Temasek Holdings,
this Israeli start-up will form a local joint venture based in Singapore in
early 2004 and initiate clinical treatment programs and clinical trials in
collaboration with SERI, SNEC and DMRI.
5. Genomics and Proteomics Research in SERI
While our genomics work in myopia and pterygium are progressing well,
a major highlight of 2003 has been our success in developing a core
proteomics platform at SERI labs through an NMRC program grant to
purchase a proteomics mass spectrometer. A major focus for 2004 will
be on the use of new proteomic technologies to pursue fundamental
research on tears, ocular surface diseases and myopia.
58
Faculty of Medicine Research Report 2003
Project Description
Grants Awarded in 2003
Genes characterizing pterygium: A common ocular surface disease
Principal Investigator
Co-Principal Investigator
: Assoc Prof Donald Tan
: Dr Leonard Ang,
Dr Phan Thong Thang,
Prof Roger W. Beuerman,
Prof Robert Lavker (USA)
Retinal Microvascular Abnomalities and Risk of
Cardiovascular Disease
Principal Investigator
Collaborator
: Dr Wong Tien Yin
: Assoc Prof Ng Tze Pin,
Assoc Prof Saw Seang Mei
: Assoc Prof Donald Tan
: Dr Bill Chan
A proteomics facility for SGH
Principal Investigator
Co-Principal Investigators
: Prof Roger W. Beuerman
: Assoc Prof Donald Tan,
Malcolm Paterson (Singhealth),
Dr Xiao (SERI),
Dr Eric Yap (DMRI),
Lei Zhao (SERI)
A Twelve-Month, Multicenter, Randomised, Double-Masked Study
to Evaluate the Efficacy and Safety of Once-daily Instillation of
Travoprost 0.004%/Timolol 0.5% and Latanoprost 0.005%/Timolol
0.5% Eye Drops in Subjects with Open-Angle Glaucoma or
Ocular Hypertension
Principal Investigator
Co-Principal Investigator
Collaborators
: Dr Simon Thom
(Imperial College London)
: Dr Wong Tien Yin
Retinal Vascular Markers And Cerebrovascular Morbidity In An
Elderly Singapore Community: The Singapore Longitudinal Study
of Aging (SLAS)
Principal Investigator
Collaborators
Principal Investigator
Collaborator
: Prof Roger W. Beuerman
: Assoc Prof Donald Tan
Tissue engineering of conjunctival and corneal stem cells for
clinical transplantation and immortalised ocular surface epithelial
stem cell derivation
Principal Investigator
Collaborators
A Singapore pilot study to evaluate the efficacy of a computerized
system for the vision improvement of people with low myopia
: Assoc Prof Paul Chew
: Dr Steve Seah (SNEC)
: Dr Lennard Thean (NUH),
Dr Clement Tan (NUH),
Dr Lim Boon Ang (SNEC),
Dr Joseph Manuel (NUH),
Dr Loon Seng Chee (NUH),
Dr Yeong Suet Ming (NUH)
Prospective Clinical Trial Assessing the Efficacies of 2
Accommodative Intraocular Lenses (IOLs) – (CrystalensTM and
AkkomodativeR HumanOptics) – in Elective hacoemulsification
Cataract Surgery
Principal Investigator
: Assoc Prof Chee Soon Phaik
Investigation of the Role of the Myocilin Gene in Primary
Angle Closure Glaucoma
Principal Investigator
Collaborators
: Dr Aung Tin
: Assoc Prof Paul Chew,
Dr Seah SK
Opening Ceremony of the First SERI-ARVO Meeting on Research in Vision
and Opthalmology with Guest of Honor, Deputy Prime Minister Tony Tan
Faculty of Medicine Research Report 2003
Tissue-engineered Cultured Conjunctival Sheet about to be used for ocular
surface transplantation
59
To evaluate the efficacy of autologous 20% human serum drops
in a variety of ocular surface disorders
Ongoing Projects
The prevalence and causes of visual impairment in
Sumatra, Indonesia
Principal Investigator
Collaborators
: Assoc Prof Saw Seang Mei
: Dr Rahat Husain,
Dr Gus Gazzard (UK),
Dr Maria Andjani,
Dr Daniel Widjaja,
Mr Mohd. Farook,
Prof David Koh,
Assoc Prof Chia Sin Eng,
Assoc Prof Wong Mee Lian,
Dr Hong Ching Ye,
Dr Jeanette Lee,
Assoc Prof Donald Tan
Principal Investigators
Collaborator
Multi-Ethnic Study of Atherosclerosis – Eye Study (MESA-Eye)
Principal Investigators
Principal Investigator
: Prof Ronald Klein (UW)
A s s e s s m e n t o f N o v e l M a r ke r s i n P t e r y g i u m a n d
Normal Conjunctivae
Principal Investigators
Collaborators
: Prof Ronald Klein (UW),
Dr Wong Tien Yin
Retinal microvascular changes and systemic vascular disease
A prospective, randomized trial evaluating the operational efficacy
of LASIK vs. PRK for the correction of low and moderate myopia
in the Singapore Armed Forces
Principal Investigators
: Dr Ti Seng Ei (SNEC),
Assoc Prof Donald Tan
: Dr Tang Jia-Yng
: Assoc Prof Donald Tan,
LTC (Dr) Benjamin Seet (SAF)
: Dr Chan Wing Kwong (SNEC),
Dr Andrew Carkeet (SERI),
Assoc Prof Saw Seang Mei,
Dr Julian Theng (SNEC),
Mr Mohd. Farook
: Assoc Prof Donald Tan,
Dr Wong Tien Yin
Corneal Disease and Corneal Transplantation Database
Principal Investigator
Collaborator
: Assoc Prof Donald Tan
: Dr Prathiba
Assessment of Novel Markers in Pterygium and Norm Conjunctivae
Principal Investigator
Collaborators
: Assoc Prof Donald Tan
: Prof Duncan Smith,
Prof Roger Beuerman
Stem cell research program (Outram Campus)
Principal Investigators
Collaborators
Primate Model of Experimental Myopia: Phase I-Genes and Early
Myopia in the Primate (Extension)
: Assoc Prof Lee Seng Teik (SGH),
Assoc Prof Donald Tan
: Assoc Prof Tay Sun Kuie,
Assoc Prof Wong Meng Cheong,
Dr Shirley Moore,
Dr Colin Song (SGH),
Dr Xiao Zhi Cheng (SGH)
Principal Investigator
Co-Principal Investigator
Collaborators
A Prospective Comparison of Primary Angle Closure: Glaucoma
Vs Primary Open Angle Glaucoma in Singapore
Principal Investigator
Collaborators
: Assoc Prof Paul Chew
: Dr Jovina See (Singhealth),
Dr Gus Guzzard (UK),
Dr Wong Hon Tym (TTSH),
Assoc Prof Saw Seang Mei,
Dr Aung Tin,
Dr Robert Ritch (US),
Dr David Garway-Heath (UK)
Collaborator
Transplantation of Autologous Cultured Conjunctival Cells for
Pterygium Surgery
Principal Investigator
Collaborators
: Assoc Prof Donald Tan
: Prof Roger W. Beuerman,
Dr Leonard Ang
Atropine in the treatment of Myopia (ATOM) Study
Principal Investigator
Collaborators
A Study to assess the affect of glaucoma on postural control with
age matched normal subjects
Principal Investigators
: Prof Roger W. Beuerman
: Assoc Prof Donald Tan
: Ms A. Barathi (SERI),
Prof Wallace Foulds (SERI)
: Assoc Prof Donald Tan
: Dr Vivian Balakrishnan,
Dr Chua Wei Han (SNEC),
Dr Louis Tong (SNEC),
Dr Yvonne Ling (SNEC)
Dr Quah Boon Long (SNEC),
Assoc Prof Saw Seang Mei
: Assoc Prof Paul Chew,
Dr Valerie Peres (CNRS)
: Dr Noor Shabana
60
Faculty of Medicine Research Report 2003
A 3rd-year Extension to a One Year Multi-Center, Double-Masked,
Placebo-Controlled,Parallel, Safety and Efficacy Study of 2%
Pirenzepine Ophthalmic Gel in Children with Myopia
Clinical Comparison of the Sovereign Phacoemulsification System
with Whitestar vs the Legacy System with Advantec Neosonic For
Cataract Extraction
Principal Investigator
Collaborators
Principal Investigator
: Assoc Prof Donald Tan
: Dr Vivian Balakrishnan,
Dr Chua Wei Han (SNEC),
Dr Louis Tong (SNEC),
Dr Quah Boon Long (SNEC)
Retinal Vascular Abnormalities As Predictors Of Cardiovascular
Disease
Principal Investigator
Analysis of Ocular Surface and Human Tears in Normal and
Diseased Eyes.
Principal Investigator
Co-Principal Investigator
Collaborators
: Prof Roger W. Beuerman
: Assoc Prof Donald Tan
: Dr Bill Lam,
Zhou Lei (SERI),
Xiong Xiang (SERI),
Dr Julian Theng (SNEC),
Dr Ti Seng Ei (SNEC),
Dr Ian Yeo (SNEC)
Detection of Early Glaucoma in Myopic Optic Nerve Heads of
East Asians using the Heidelberg Retina Tomograph II
Principal Investigator
Collaborators
: Assoc Prof Paul Chew
: Dr Zheng Ce,
Dr Wong Hon Tym (TTSH),
Dr David Garway-Heath (UK)
Systemic Autonomic Functions and Postural Stability in AngleClosure Glaucoma
Principal Investigator
Collaborators
: Assoc Prof Paul Chew
: Dr Valerie Peres (CNRS),
Dr Noor Shabana,
Dr Jovina See (Singhealth),
Dr Clement Tan (NUH),
Assoc Prof James Goh,
Dr Ho Ching Lin (SNEC),
Assoc Prof E. Wilder Smith
Changes in the Refractive Components in Myopic &
Emmetropic Eyes
Principal Investigator
Co-Principal Investigator
Collaborators
: Assoc Prof Saw Seang Mei
: Assoc Prof Donald Tan
: Dr Chua Wei Han (SNEC),
Dr Louis Tong (SNEC),
Dr Wu Hui Min (DMRI),
Dr Hong Ching Ye,
Dr Andrew Carkeet (SERI),
Dr Rose Vaithinathan (SHS)
Principal Investigator
Collaborators
: Dr Aung Tin
: Prof Shomi Bhattacharya (London),
Prof Koji Okada (Japan),
Dr G Kumaramanickavel (India)
Phase 2 study of Pirenzepine Ophthalmic Gel in controlling myopia
progression
Principal Investigator
Collaborators
: Assoc Prof Donald Tan
: Dr Vivian Balakrishnan,
Dr Chua Wei Han (SNEC),
Dr Louis Tong (SNEC),
Dr Quah Boon Long (SNEC)
A Multi-Centre, Investigator-Marked, Randomised, Parallel,
6-Month Study (With treatment Extended to 12 months) of the
Safety & Efficacy of Lumigan 0.03% Ophthalmic Solution
Compared with Latanoprost 0.005% Ophthalmic Solution
Administered Adjunctively with Timolol Ophthalmic Solution, In
patients with Glaucoma or Ocular Hypertension
Principal Investigator
Collaborators
: Assoc Prof Paul Chew
: Dr Ho Ching Lin (SNEC),
Dr Wong Hong Tym (TTSH)
A Twelve-Week, Double-Blind, Parallel Group, Primary Therapy
Study of the Safety and Efficacy of Travoprost 0.004%
compared to Latanoprost 0.005% in patients with Chronic-Angle
Closure Glaucoma
Principal Investigator
Collaborators
: Prof Roger W. Beuerman
: Assoc Prof Donald Tan
: Ms A Bharati (SERI),
Ms Sung Rhan (SERI),
Ms Jamie Chew (SERI)
Faculty of Medicine Research Report 2003
: Dr Wong Tien Yin
Investigating the role of the OPA1 gene in normal tension
glaucoma patients in Singaporeans.
Aetiology of Myopia
Principal Investigator
Co-Principal Investigator
Collaborators
: Assoc Prof Chee Soon Phaik
61
: Assoc Prof Paul Chew
: Dr Lennard Thean (NUH),
Dr Lim Boon Ang (SNEC),
Dr Hoh Sek Tien (SNEC),
Dr Clement Tan (NUH),
Dr Vernon Yong (TTSH),
Dr Loon Seng Chee (NUH),
Dr Alejandro Chung (NUH),
Dr Lee Sao Bing (Singhealth)
S. E. Ti and D. T. Tan
International Publications
Tectonic corneal lamellar grafting for severe scleral melting after
pterygium surgery. Ophthalmology 2003; 110 (6):1126-1136.
T. Aung, K. Okada, D. Poinoosawmy, L. Membrey, G. Brice, A. H. Child,
S. S. Bhattacharya, O. J. Lehmann, D. F. Garway-Heath and R. A. Hitchings
The phenotype of normal tension glaucoma patients with and
without OPA1 polymorphisms. British Journal of Ophthalmology.
2003; 87 (2):149-152.
S. L. Tow, T. Aung, F. T. Oen and S. K. Seah
Combined phacoemulsification, intraocular lens implantation and
trabeculectomy for chronic angle closure glaucoma. International
Ophthalmology. 2003; 24 (5):283-289.
S. Y. Lee, S. P. Chee, V. Balakrishnan, S. Farzavandi and D. T. Tan
Surodex in paediatric cataract surgery. British Journal of
Ophthalmology. 2003; 87 (11):1424-1426.
Shen, W. Y., Lee, S. Y., Yeo, Y. S. I., Lai, C. M., Mathur, R., Tan, Donald T. H.,
Constable, I.J. and Rakoczy, P. E
Predilection of the macular region to high incidence of choroidal
neovascularization after intense laser photocoagulation in the
monkey. Archives of Ophthalmology. 2003.
J. T. Theng, T. S. Ei, L. Zhou, K. W. Lam, S. P. Chee and D. Tan
Aung T, Ebenezer ND, Brice G, Child AH, Prescott Q, Lehmann OJ, Hitchings
RA and Bhattacharya SS
Prevalence of optineurin sequence variants in adult primary open
angle glaucoma: Implications for diagnostic testing. 2003;
40: e101.
S. K. Seah, G. Gazzard and T. Aung
Intermediate-term outcome of Baerveldt glaucoma implants in
Asian eyes. Ophthalmology 2003; 110 (5):888-894.
A. Carkeet, S. Velaedan, Y. K. Tan, D. Y. Lee and D. T. Tan
Higher order ocular aberrations after cycloplegic and noncycloplegic pupil dilation. Journal of Refractive Surgery. 2003;19
(3):316-322.
C. M. Chan, J. T. Theng, L. Li and D. T. Tan
Pharmacokinetic and toxicity study of an intraocular cyclosporine
DDS in the anterior segment of rabbit eyes. Investigative
Ophthalmology and Visual Science. 2003; 44 (11):4895-4899.
N. Shabana, V. C. Peres, A. Carkeet and P. T. Chew
Motion perception in glaucoma patients: a review. Survey of
Ophthalmology. 2003; 48 (1):92-106.
G. Gazzard, D. S. Friedman, J. G. Devereux, P. Chew and S. K. Seah
A prospective ultrasound biomicroscopy evaluation of changes
in anterior segment morphology after laser iridotomy in Asian
eyes. Ophthalmology 2003; 110 (3):630-638.
G. Gazzard, P. J. Foster, J. G. Devereux, F. Oen, P. Chew, P. T. Khaw and
S. Seah
Microsporidial keratoconjunctivitis in healthy individuals: a case
series. Ophthalmology 2003; 110 (7):1420-1425.
Intraocular pressure and visual field loss in primary angle closure
and primary open angle glaucomas. British Journal of
Ophthalmology. 2003; 87 (6):720-725.
C. R. Hicks, G. J. Crawford, X. Lou, D. T. Tan, G. R. Snibson, G. Sutton, N.
Downie, L. Werner, T. V. Chirila and I. J. Constable
G. Gazzard, W. Morgan, J. Devereux, P. Foster, F. Oen, S. Seah, P. T. Khaw
and P. Chew
Corneal replacement using a synthetic hydrogel cornea, AlphaCor
trade mark : device, preliminary outcomes and complications. Eye
2003; 17 (3):385-392.
Optic disc hemorrhage in Asian glaucoma patients. Journal of
Glaucoma. 2003; 12 (3):226-231.
C. R. Hicks, G. J. Crawford, D. T. Tan, G. R. Snibson, G. L. Sutton, N. Downie,
T. D. Gondhowiardjo, D. S. Lam, L. Werner, D. Apple and I. J. Constable
S. M. Saw, G. Gazzard, D. S. Friedman, P. J. Foster, J. G. Devereux, Wong
M L and S. Seah
AlphaCor cases: comparative outcomes. Cornea 2003; 22 (7):
583-590.
Awareness of glaucoma and health beliefs of patients suffering
primary acute angle closure. British Journal of Ophthalmology
2003; 87 (4):446-449.
K. Y. Lee, G. Gazzard and D. T. Tan
S. M. Saw, G. Gazzard, K. G. Eong and D. Koh
Ciliary body arteriovenous malformation? Eye 2003; 17 (5):
658-659.
62
Utility values and myopia in teenage school students. British
Journal of Ophthalmology 2003; 87 (3):341-345.
Faculty of Medicine Research Report 2003
S. M. Saw, G. Gazzard and D. S. Friedman
L. Zhou, R. W. Beuerman, A. Barathi and D. Tan
Interventions for angle-closure glaucoma: an evidence-based
update. Ophthalmology 2003; 110 (10):1869-1878.
Analysis of rabbit tear proteins by high-pressure liquid
chromatography/electrospray ionization mass spectrometry. Rapid
communications in mass spectrometry: RCM.2003; 17 (5):401412.
S. M. Saw, R. Husain, G. M. Gazzard, D. Koh, D. Widjaja and
D. T. Tan
Causes of low vision and blindness in rural Indonesia. British
Journal of Ophthalmology. 2003; 87 (9):1075-1078.
Si Z, Palkama A, Gebhardt BM, Velasquez D; Galeano MJ and
Beuerman RW
T. Y. Wong and D. T. Tan
Distribution of thrombospondin-4 in the bovine eye, Current Eye
Research, 2003; 27(3): 165-173.
The SERI-ARVO Meeting and future challenges of ophthalmic
research in Asia. British Journal of Ophthalmology. 2003; 87
(4):379-380.
T. Y. Wong, P. J. Foster, G. J. Johnson and S. K. Seah
Refractive errors, axial ocular dimensions, and age-related
cataracts: the Tanjong Pagar survey. Investigative Ophthalmology
and Visual Science. 2003; 44 (4):1479-1485.
Xiong X, Barathi A, Beuerman RW and Tan DT
Assay of leucine aminopeptidase activity in vitro using largepore reversed phase chromatography with fluorescence detection,
Journal of Chromatography B, 2003 ;796(1): 63-70.
Avunduk AM, Beuerman RW, Warnel ED, Kaufman HE and Greer D
T. Y. Wong, B. E. Klein, R. Klein, M. Knudtson and K. E. Lee
Comparison of efficacy of topical and oral fluconazole treatment
in experimental Aspergillus keratitis, Current Eye Research, 2003;
26(2): 113-117.
Refractive errors, intraocular pressure, and glaucoma in a white
population. Ophthalmology 2003; 110 (1):211-217.
Awasthi D, Kutz SC, Beuerman RW, Nguyen D, Carey ME and Zeiller S
T. Y. Wong, R. Klein, A. R. Sharrett, T. A. Manolio, L. D. Hubbard, E. K.
Marino, L. Kuller, G. Burke, R. P. Tracy, J. F. Polak, J. S. Gottdiener and D.
S. Siscovick
Early gene expression in the rat cortex after experimental traumatic
brain injury and hypotension, Neuroscience Letters, 2003, 10:345(1)
: 29-32.
The prevalence and risk factors of retinal microvascular
abnormalities in older persons: The Cardiovascular Health Study.
Ophthalmology 2003; 110 (4):658-666.
Avunduk AM, Beuerman RW, Varnell ED and Kaufman HE
T. Y. Wong, R. Klein, F. J. Nieto, B. E. Klein, A. R. Sharrett, S. M. Meuer, L.
D. Hubbard, and J. M. Tielsch
Wong TY, Mosley T, Klein R, Klein BEK, Sharrett AR, Couper DJ and
Hubbard LD
Retinal microvascular abnormalities and 10-year cardiovascular
mortality: a population-based case-control study. Ophthalmology
2003; 110 (5):933-940.
Retinal microvascular abnormalities and MRI signs of cerebral
atrophy in healthy, middle-aged people. Neurology 2003; 61:
806-811.
T. Y. Wong, R. Klein, B. E. Klein, S. M. Meuer and L. D. Hubbard
Moss S, Klein R, Klein BEK and Wong TY
Retinal vessel diameters and their associations with age and
blood pressure. Investigative Ophthalmology and Visual Science.
2003; 44 (11):4644-4650.
Retinal vascular changes and 20-year incidence of lower extremity
amputations in a cohort with diabetes. Archives of Internal
Medicine 2003; 163:2505-2510.
P. J. Foster, D. Machin, T. Y. Wong, T. P. Ng, J. F. Kirwan, G. J. Johnson, P.
T. Khaw and S. K. Seah
Klein R, Klein BEK, Moss S, Wong TY, Hubbard LD and Cruickshanks KJ
Determinants of intraocular pressure and its association with
glaucomatous optic neuropathy in Chinese Singaporeans: the
Tanjong Pagar Study. Investigative Ophthalmology and Visual
Science. 2003; 44 (9):3885-3891.
P. J. Foster, T. Y. Wong, D. Machin, G. J. Johnson and S. K. Seah
Risk factors for nuclear, cortical and posterior subcapsular cataracts
in the Chinese population of Singapore: the Tanjong Pagar Survey.
British Journal of Ophthalmology. 2003; 87 (9):1112-1120.
Faculty of Medicine Research Report 2003
Confocal microscopy of Aspergillus fumigatus keratitis, British
Journal of Ophthalmology, 2003; 87(4): 409-410.
Retinal vascular abnormalities in persons with Type 1 diabetes.
The Wisconsin Epidemiological Study of Diabetic Retinopathy.
Ophthalmology 2003; 110: 2118-2125.
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R and Klein BEK
A revised method for summarizing retinal vessel diameters.
Current Eye Research 2003; 27:143-149.
Wang JJ, Mitchell P, Leung H, Rochtchina E, Wong TY and Klein R
Hypertensive retinal vessel wall signs in the general older
population: the Blue Mountains Eye Study. Hypertension 2003;
42: 534-541.
63
Tan AG, Wang JJ, Rochtchina E, Klein R, Wong TY, Hubbard LD and
Mitchell P
Correlation between generalised and focal retinal arteriolar
narrowing in an older population. Clinical and Experimental
Ophthalmology 2003; 31:322-325.
Staff Profile
Associate Professor & Head
Associate Professors
:
:
Assistant Professors
:
Adjunct Professor
Adjunct Associate Professor
Clinical Professor
:
:
:
Wong TY
Cerebral white matter lesions, retinopathy and stroke. Stroke
2003; 34: e212.
Leung H, Wang JJ, Rochtchina E, Tan AG, Wong TY, Hubbard LD, Klein R
and Mitchell P
Computer-assisted retinal vessel measurement in an older
population: Correlation between right and left eyes. Clinical and
Experimental Ophthalmology 2003; 31:326-330.
Contact Information
Leung H, Wang JJ, Rochtchina E, Tan AG, Wong TY, Klein R, Hubbard LD
and Mitchell P
Relationships between age, blood pressure and retinal vessel
diameters in an older population. Investigative Ophthalmology
and Visual Sciences 2003; 44:2900-2904.
Contact Person
:
Telephone
:
Wong TY, Klein R, Duncan BB, Nieto FJ, Klein BEK, Couper DJ, Hubbard
LD and Sharrett AR
Facsimile
Email
Postal Address
:
:
:
Racial difference in the prevalence of hypertensive retinopathy.
Hypertension 2003;41: 1086-1091.
Zhang MZ, Lim ASM and Wong TY
A pilot study of lens extraction in the management of acute
primary angle-closure glaucoma. American Journal of
Ophthalmology 2003; 135: 534-536.
L P K Ang, E Y Yap and H B Fam
Ophthalmic Artery and Central Retinal Vein Occlusion in Primary
Antiphospholipid Syndrome. Eye 2003.
Yip LWL and Au Eong KG
Recurrent subretinal haemorrhages and progressive lacquer cracks
in a high myope. Acta Ophthalmologica Scandinavica 2003; 81(6):
646-657.
Ng EW, Joo MJ, Au Eong KG, Green WR and O’Brien TP
Ocular toxicity of intravitreal trovafloxacin in the pigmented
rabbit. Current Eye Research 2003; 27(6):387-393.
F M Chan, R Mathur, J J Ku, C Chen, S P Chan, V S Yong and K G Au Eong
Short-term outcomes in eyes with posterior capsule rupture during
cataract surgery. Journal of Cataract and Refractive Surgery. 2003;
29 (3):537-541.
64
Tan Tiang Hwee, Donald
Chew Tec Kuan, Paul
Chee Soon Phaik
Saw Seang Mei
(secondary appointment)
Wong Tien Yin
Ang Pek Kiang, Leonard
Aung Tin
Roger W. Beuerman
Au Eong Kah Guan
Lim Siew Ming, Arthur
Faculty of Medicine Research Report 2003
Assoc Prof Donald Tan
Head of Department
6772-5311
6772-5316
6777-7161
ophhead@nus.edu.sg
Department of Ophthalmology
National University of
Singapore
5 Lower Kent Ridge Road
Singapore 119074
INTRODUCTION
The Department is constantly at the forefront of research and technological
advances, so as to enable better understanding of the various
musculoskeletal disorders, develop innovative solutions to clinical problems
and implement new treatment and management modalities to improve
medical care.
The three main focus areas of research are in cell and molecular including
tissue engineering, mammalian tissue and bioengineering, which
have important cutting edge technologies for orthopaedic practice in
the future.
The Tissue Engineering Research Group has pioneered exciting
breakthroughs in tissue engineering, including a human clinical trial for
the repair of articular cartilage, regeneration of tendon and ligament in
vivo and development of bioresorbable three dimensional scaffolds as
carriers for cells and growth factors.
The Cell and Molecular Research Group currently has a number of grants
looking into the cellular and molecular mechanisms in bone physiology,
which includes osteoclast development and function in relation to
pathological bone resorption and osteoporosis; cellular and molecular
mechanisms in the development of osteoarthritis; and bone healing by
osteoblasts. The Muscle Group have developed a new motality that fully
optimizes the use of muscles for tendon transfers, by engineering one
muscle into two independent sub-units for transfer, and classified skeletal
muscles by relating muscle shape and morphology to intramuscular
innervation and muscle function.
The Spine Research Group has developed a novel contoured spinal fixation
device for lumbar interbody fusion in Asians and is studying the in vivo
fusion performance of this biodegradable device in a non human primate
model. Other research highlights include the biomechanical assessment
of the skin to help in the assessment of flap shrinkage, the construction
of a bioreactor to apply hydrostatic loading to regulate the metabolism
of cultured chondrocytes, and study of the interaction between
angiogenesis and osteosarcoma.
Faculty of Medicine Research Report 2003
65
DEPARTMENT OF
Orthopaedic Surgery
Multisensory skin flap planning assistance using a virtual
model of patient – specific biomechanics and blood supply
Project Description
Principal Investigator
Collaborators
: Assoc Prof Lim Beng Hai
: Dr Etienne Burdet,
Dr Timothy Poston
(John Hopkins Singapore),
Dr Alphonsus Chong (NUH),
Dr Amitabha Lahiri (NUH),
Dr Lim Kian Meng,
Dr Chew Chee Meng,
Dr Teo Chee Leong,
Dr Chen Chao Yu Peter
Grants Awarded in 2003
To compare the effects of passive range of motion of the knee
on the Less Invasive Stabilization System – Distal Femur (LISSDF) plate system with the antegrade and the retrograde femoral
nail in comminuted distal femoral fractures
Principal Investigator
Collaborator
: Dr Hee Hwan Tak
: Mr Ashvin Thambyah
The effects of graft enhancement using autologous mesenchymal
stem cells on osteointegration and the minimum graft length of
hamstring tendon grafts in a porcine model of anterior cruciate
ligament reconstruction
Principal Investigator
Collaborator
Principal Investigator
Co-Principal Investigators
: Dr James Hui
: Prof Lee Eng Hin
Distal radioulnar joint reconstruction – 4 strand technique:
Cadveric evaluation of load bearing ability and range of movement
Principal Investigator
Collaborators
A study on fusion performance of the novel contoured spinal
fixation device in conjunction with stem cells and bone
morphogenetic proteins in lumbar interbody fusion
: Assoc Prof Lim Beng Hai
: Dr James Loh (CGH),
Mr Ashvin Thambyah
Tissue engineering approaches to the repair and regeneration of
anterior cruciate ligament
Principal Investigator
Co-Principal Investigators
The regeneration of articular cartilage using hyaluronic acid
scaffolds – An animal study
Principal Investigator
Collaborators
Principal Investigator
Co-Principal Investigators
: Assoc Prof Lim Beng Hai
: Dr Alphonsus Chong (NUH),
Assoc Prof James Goh,
Dr James Hui,
Prof Lee Eng Hin
: Prof Lee Eng Hin
: Assoc Prof James Goh,
Dr James Hui,
Dr Suresh Nathan (NUH),
Dr Lim Sai Kiang (GIS),
Assoc Prof Cao Xinmin (IMCB),
Dr Li Jun (IMRE)
Ongoing Projects
Development of an intramedullary fixation device for
metacarpal fractures
Principal Investigator
Collaborators
: Assoc Prof James Goh
: Prof Lee Eng Hin,
Adj Prof Casey Chan,
Assoc Prof Toh Siew Lok,
Dr Graeme Guy (IMCB),
Dr James Hui
Tissue engineering in musculoskeletal tissues: Characterizing and
defining the cellular and molecular mechanisms and their role in
tissue integration
: Prof Lee Eng Hin
: Assoc Prof James Goh,
Dr James Hui
The influence of bone marrow derived mesenchymal stromal
cells on rate of tendon healing in rabbits
Principal Investigator
Collaborators
: Assoc Prof Wong Hee Kit
: Assoc Prof James Goh,
Dr Li Baojie (IMCB),
Dr Dietmar Hutmacher
: Assoc Prof Lim Beng Hai
: Dr Alphonsus Chong (NUH),
Assoc Prof Chou Siaw Meng (NTU)
The effects of load carrying on the posture and gait of normal
and scoliotic adolescents
Principal Investigator
Collaborators
: Assoc Prof Wong Hee Kit
: Assoc Prof James Goh,
Ms Chan Pui Yee
Effect of OP-1 in enhancing anterior lumbar interbody fusion
using allografts
Principal Investigator
Collaborators
66
: Assoc Prof Aziz Nather
: Dr Suresh Nathan (NUH),
Dr David Wong (NUH)
Faculty of Medicine Research Report 2003
Using tissue engineering to produce biologically active bone
allografts for orthopaedic surgery and oral maxillo-facial surgery
Principal Investigator
Collaborators
: Assoc Prof Aziz Nather
: Assoc Prof Ho Kee Hai,
Dr David Vikram (NUH),
Ms Wang Li Hui
Defence Science Technology Agency (DSTA) - Finite element
modeling of the cervical vertebrae in high + GZ environment
Principal Investigators
Collaborators
: Assoc Prof James Goh,
Assoc Prof Victor Shim
: Assoc Prof Toh Siew Lok,
Dr Peter Lee (DMRI)
Nerve regeneration and recovery following surgical decompression
of sustained spinal nerve root compression: Role of neutropic
agents in an experimental animal model
Principal Investigator
Collaborator
: Assoc Prof Wong Hee Kit
: Dr Yu Zhirong (NUH)
The application of a bioresorbable 3D scaffold and mesencymal
stem cells for tissue engineering an osteochondral transplant
Principal Investigator
Collaborators
: Prof Lee Eng Hin
: Assoc Prof James Goh,
Prof Teoh Swee Hin,
Dr Dietmar Hutmacher
Use of synthetic porous biodegradable polymer sheets for ligament
tissue engineering
Principal Investigator
Collaborators
: Assoc Prof James Goh
: Prof Lee Eng Hin,
Prof Casey Chan,
Prof Teoh Swee Hin
Digital pre-training in microsurgery
Principal Investigator
Collaborator
: Assoc Prof Lim Beng Hai
: Dr Timothy Poston
(John Hopkins Singapore)
Gross morphology of osteochondral defect repair in rabbit’s knee at 6 months.
Experimental side showed the defect was totally repaired by cartilage like
tissue and integrated smoothly with surrounding host tissue
Intra-articular injection of microsphere-encapsulated chondroitin
sulphate for the treatment of osteoarthritis in a rabbit model
International Society of Prosthetics and Orthotics (ISPO):
Mechanical testing of prosthetic ankle foot devices
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Dr James Hui
: Prof Lee Eng Hin,
Assoc Prof James Goh,
Assoc Prof Lim Lee Yong,
Dr Fong Chee Wai (IMCB)
A study of mechanical factors related to osteoarthritis
Principal Investigator
Collaborators
: Mr Ashvin Thambyah
: Assoc Prof James Goh,
Dr P Thiagarajan
(Mount Elizabeth Medical Centre)
Principal Investigator
: Prof Robert Pho
: Assoc Prof Kong Hwai Loong,
Dr Ivor Lim,
Dr Phan Toan Tong
Use of cultured mesenchymal stem cells on repair of chondral
defects in humans
Principal Investigator
Collaborators
Principal Investigator
Collaborator
: Dr Wilson Wang
: Prof Shamal Das De
Factor of safety in ligaments: A study of the physiological strains
of ligaments relative to its ultimate load
: Mr Ashvin Thambyah
: Prof K Satku
: Prof Robert Pho
Angiogenesis In Osteosarcoma
Principal Investigator
Collaborators
Effects of biomaterial particle phagocytosis on the characteristics
and function of osteoclasts
Principal Investigator
Collaborator
Cosmetic Prosthesis Project
: Assoc Prof James Goh
: Dr Peter Lee (DMRI),
Mr Steen Jensen (ISPO)
: Prof Lee Eng Hin
: Dr James Hui,
Prof Shamal Das De
Faculty of Medicine Research Report 2003
Design and development of a system to apply hydrostatic pressure
stimuli to regulate cell metabolism in cultures used in
musculoskeletal tissue
Principal Investigator
Collaborators
: Prof K Satku
: Mr Ashvin Thambyah,
Mr Shabbir Moochalla (DSTA),
Mr Achuth Narayan (DSTA)
Effects of tumour necrosis factor on the development, formation,
function and characteristics of osteoclasts
Principal Investigator
Collaborator
67
: Dr Wilson Wang
: Prof Shamal Das De
Characterization of mesenchymal stem cells isolated from animal
and human tissues
Principal Investigator
Collaborators
: Dr James Hui
: Dr Suresh Nathan (NUH),
Prof Lee Eng Hin,
Assoc Prof James Goh,
Prof Shamal Das De
Chen F, Hui JH, Chan WK and Lee EH
Cultured mesenchymal stem cell transfers in the treatment of
partial growth arrest. J Pediatr Orthop 2003;23(4):425-9.
A detailed investigation of the intra-muscular anatomy and
physiology of skeletal muscles to maximize the role and potential
of neuromuscular compartments for novel surgical procedures in
limb reconstruction
Principal Investigator
Collaborators
: Prof VP Kumar
: Mr Barry Pereira,
Mr Aymeric YT Lim (NUH)
: Dr Wilson Wang
: Dr L Krishna (NUH),
Prof K Satku
Pulmonary function and scoliosis in children with spinal muscular
atrophy types II and III. J Paediatr Child Health. 2003 ;39(9): 673676.
Reverse anterior tibial artery flap for reconstruction of foot donor
site. Plast Reconstr Surg 2003;112(6):1604-12
Fujihara K, Xheng-Ning Huang, Ramakrishna S, Satkunanantham K and
Hamada H
Performance study of braided carbon/PEEK composite compression
bone plates. Biomaterials 2003; 24:2661-7.
Clinical and Biomechanical Evaluation of Hydrostatic
Prosthetic Socket for Transtibial Amputees Using A Novel Quick
Curing Material
Principal Investigator
Collaborators
Chng SY, Wong YQ, Hui HP, Wong HK, Ong HT and Goh D
Dong JS, Peng YP, Zhang YX, Lim BH and Pho RW
Investigation of VEGF and VEGFR expression in osteoarthritic
articular cartilage
Principal Investigator
Collaborators
International Publications
: Assoc Prof James Goh
: Dr Peter Lee (DMRI),
Dr William Chan (TTSH),
Mr Ho Kam Wa (TTSH)
Goh JCH, Ouyang HW, Teoh SH, Chan CK and Lee EH
Tissue engineering approach to the repair and regeneration of
tendons and ligaments. Tissue Eng 2003; 9(1):S31-44.
Goh J, Lee PVS and Chong SY
Static and dynamic pressure profile of the patellar tendon bearing
(PTB) socket. Proc Inst Mech Eng (H) 2003; 217(2):127-6.
Goh JCH, Lee PVS and Chong SY
Stump/Socket pressure Cast Prosthetic Socket. Clin Biomech
(Bristol, Avon) 2003; 18:238-43.
Hee HT, Majd ME, Holt RT, Whitecloud TS and Pienkowski D
Complications of multilevel cervical corpectomies and
reconstruction with titanium cages and anterior plating. J Spinal
Disord 2003; 16:1-8.
Hee HT, Singh S, Chong SM and Myers L
Protective effects of growth hormone on physeal distraction: an
experimental study on rabbits. J Pediatrics Orthop B 2003; 12(5):
332-7.
PDCAST socket for transtibal amputees
Hee HT, Majid ME, Holt RT and Myers L
Do autologous growth factors enhance transforaminal lumber
interbody fusion? Eur Spine J 2003; 12(4):400-7.
Hee HT, Whitecloud TS and Myers L
The effect of previous low back surgery on general health statusresults from the National Spine Network initial visit survey. Eur
Spine J 2003;12S:12
68
Faculty of Medicine Research Report 2003
Hee HT, Yu ZR, Wong D and Wong HK
Satkunanantham K, Kumar VP, Chong SM and Thambyah A
Early results of thoracoscopic instrumented fusion versus
conventional posterior instrumented fusion in type-3 adolescent
idiopathic scoliosis. Eur Spine J 2003;12S:27
The natural history of spontaneous osteonecrosis of the
medial tibial plateau. J Bone Joint Surg Br 2003;85(7):
983-8
Hua J, Kumar VP, Tay SSW and Pereira BP
Thambyah A, Hee HT, Das De S and Lee SM
Microscopic changes at the neuromuscular junction in free muscle
transfer. Clin Orthop 2003; 411:325-33.
Gait adaptations of patients with longstanding hip fusion.
J Orthop Surg. 2003;11(2):154-8.
Hui JHP and Torode IP
Changing glenoid version after open reduction of shoulders in
children with obstetric brachial plexus palsy. J Pediatr Orthop
2003;23(1):109-13.
Hui HP and Marchie A
Staff Profile
Professor & Head
Professors
:
:
Adjunct Professor
Associate Professors
:
:
Adjunct Associate Professor
Assistant Professors
:
:
Research Fellows
:
Research Assistants
:
Current management of cartilage defects. J Rheumatol 2003;6:17077
Lee EH and Hui HP
Stem cell research and paediatric orthopaedics. J Pediatr Orthop
2003; 23(4):1-2.
Lee EH
The SARS war: Back to basic (Editorial). J Orthop Surg 2003;11
(1):1-2
Nathan S, Das De S, Thambyah A, Fen C, Goh J and Lee EH
Cell based therapy in the repair of osteochondral defects: A novel
use of adipose tissue. Tissue Eng 2003; 9(4):733-44.
Nathan S, Aleem MA, Thiagarajan P and Das De S
The incidence of proximal deep vein thrombosis following total
knee arthroplasty in an Asian population: a Doppler ultrasound
study. J Orthop Surg. 2003;11(2): 184-9.
K Satkunanantham
Robert Pho
Lee Eng Hin
V Prem Kumar
Shamal DasDe
Casey Chan
Lim Beng Hai
Wong Hee Kit
Aziz Nather
James Goh
Khong Kok Sun
James Hui
Wilson Wang
Hee Hwan Tak
Dietmar Hutmacher
(joint appointment)
Ashvin Thambyah
Barry Pereira
Li Li
Shao XinXin
Li Lin
Ge Zigang
Kanakkapillai
Mohamed Ismail
Cheong Chee Hoong
Ouyang HW, Goh JCH, Thambyah A, Teoh SH and Lee EH
Knitted PLGA scaffold loaded with bone marrow stromal cells in
repair and regeneration of rabbit Achilles tendon. Tissue Eng
2003; 9(3)431-9.
Contact Information
Contact Person
:
Continous local anaesthesia for post-operative mobilization of
injured digits. J Hand Surg (Br) 2003;28(6):513-9
Telephone
Facsimile
Email
:
:
:
Ranggapa S, Chen Fen, Lee EH, Bongso TA and Sim EWK
Contact Person
:
Telephone
Facsimile
Email
Postal Address
:
:
:
:
Homepage
:
Peng YP, Seow C, Low CK, Chew WY and Pho RW
Transformation of adult mesenchymal stem cells isolated from
the fatty tissue into cardiomyocytes. Ann Thorac Surg 2003;
75:775-9.
Faculty of Medicine Research Report 2003
69
Prof V Prem Kumar
Research Director
6772-4322
6778-0720
doskumar@nus.edu.sg
Assoc Prof James Goh
Research Director
6772-4423
6774-4082
dosgohj@nus.edu.sg
Department of Orthopaedic
Surgery
National University of
Singapore
5 Lower Kent Ridge Road
Singapore 119074
http://www.med.nus.edu.sg/os/
INTRODUCTION
Department of Otolaryngology is a department with 4 academic clinical
staff, 2 full time research scientists, and 3 overseas visiting professors.
We are complemented by 4 clinical staff from NUH to increase our patient
based research. The strategy of our Department is to develop focused
areas of research based on the questions which are encountered in
relevant clinical practice. Our immediate focus in research is to build up
a nasopharyngeal cancer program and a rhinologic immunology program.
Over the next few years, we will expand our research activities to cover
thyroid cancer and paediatric Otolaryngology. Recently, we have also
expanded our research interests into clinical application of genetic
predisposition and gene-environmental interaction on disease expression
of the above diseases.
DEPARTMENT OF
Otolaryngology
There has been increasing intra-departmental and international
collaborations in our Department. The Department has a Director of
Research who assists the Head in coordinating research activities and
collaborations, and regular monthly departmental research meeting in
order to share research initiatives, new findings and problems encountered.
Our staff are PIs of several BMRC, NMRC, NHG, and university research
projects and collaborators of several multidisciplinary research projects.
One of our research projects received 2003 Sam Sanders Award for Basic
Science from the American Academy of Otolaryngic Allergy (AAOA).
70
Faculty of Medicine Research Report 2003
The major research themes include:
Nasopharyngeal Cancer Program
We have a database in excess of 300 NPC patients collated over the past
few years that form a good base for our research. There is collaboration
with international institutions such as Johns Hopkins, Karolinksa which
have resulted in publication of new knowledge in somatostatin receptors,
COX-2, EGFR, Epigenetics, serum EBV quantifications, T-cell functions in
NPC. Our clinical research involves phase 2 trials with chemoradiation
protocols for late staged NPC and concomitant boost for early staged
NPC. Both of the latter trials have been completed and presented at
international meetings. We have an on going trial looking at the presence
of serum EBV quantity in first degree family members with NPC(NMRC
funded trial). Finally, the large multi-specialty practice involving Head
and Neck Surgery, Radiation Oncology, Medical Oncology, Plastic Surgery,
MaxilloFacial Surgery, Speech Therapy, Audiology and Diagnostic Imaging
provide a large number of research projects that can be undertaken.
Rhinology and Allergy
Our research interests cover several clinical and basic research areas
(community survey, development of dynamic and functional airway
examinations, investigation of genetic and epigenetic mechanisms,
immunohistochemical identification of inflammatory cells and T cell
functions) in order to contribute to a deeper understanding into the
immunological mecha nisms and development of therapeutic interventions
for rhinitis, sinusitis and nasal polyposis.
Cochlear physiology and inner ear medication
This is to study the feasibility of virus-mediated transgene delivery
into the inner ear through an intact round window membrane for
treatment of inner ear disorders. Our study reflects a trend towards
administration of medication through a topical application so that the
drug bypasses the circulation to go straight to the inner ear for maximal
therapeutic effects, which minimized the side effects resulting from the
systemic application.
Faculty of Medicine Research Report 2003
71
DEPARTMENT OF
Otolaryngology
The role of proinflammatory cells and cytokines in the
pathogenesis of sinusitis and nasal polyps: with
immunohistochemical characterization
Project Description
Principal Investigator
Collaborators
Grants Awarded in 2003
: Dr Wang De Yun
: Prof Yeoh Kian Hian,
Naresh Chachlani
EBV DNA screening in familiar Nasopharyngeal Cancer
Etiology and pathogenesis of otitis media in Singapore
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Assoc Prof Tan Kim Siang, Luke
: Loh Woei Shyang,
Dr Thomas Loh,
Dr Wenson Hsieh
Ongoing Projects
International Publications
Genetic polymorphisms of candidate genes in chromosome 5q3133 in atopic and allergic rhinitis in Singapore population
Principal Investigator
Collaborators
: Dr Wang De Yun
: Dr Heng Chew Kiat,
Mr Cheung Wai, Wilson
Cochlear delivery of neurotrophic factors by gene transfer through
an intact round window membrane for treatment of profound
hearing loss
Principal Investigator
Collaborator
: Assoc Prof Tan Kun Kiaang, Henry
: Gamini Kumarasinghe (NUH),
Dr Wang De Yun
: Dr Ruan Run-sheng
: Assoc Prof Ge Rowen
(Department of Biological Science)
ZQ Chen, ML Duan, RS Ruan, HS Lee, M Ulfendahl
Pharmacokinetics of caroverine in inner ear perilymph and its
effects on cochlear function after systemic and local adminstrations
in guinea pigs, Audiol Neurootol 2003; 8: 49-56.
ZQ Chen, ML Duan, RS Ruan, M Ulfendahl
Acute treatment of noise trauma with local caroverine application
in guinea pig, act. Otolaryngl (Stokhol), 2003; 123: 905-909.
Wang DY, Goh DYT, Ho AKL, Chew FT, Yeoh KH, Lee BW
The upper and lower airway responses to nasal challenge with
house dust mite Blomia tropicalis. Allergy; 2003; 58: 78-82.
Clinical manifestations of food allergy - a double blind, placebo
controlled food challenge study
Bunnag C, Dr Suprihati, Wang DY
Principal Investigator
Collaborator
Patient preference and sensory perception of three intranasal
glucocorticosteroids for allergic rhinitis. Clin Drug Invest 2003;
23: 39-44.
: Prof Yeoh Kian Hian
: Dr Wang De Yun
Inner ear gene transfer for treatment of profound hearing loss
Zhang PC, Pang YT, Loh KS, Wang DY
Principal Investigator
Collaborator
Comparison of histology between recurrent tonsillitis and tonsillar
hypertrophy. Clin Otolaryngol 2003; 28: 235-239.
: Dr Ruan Run-sheng
: Prof Yeoh Kian Hian
Huang ZL, Ong KL, Goh SY, Liew HL, Yeoh KH, Wang DY
Assessment of nasal cycle by Acoustic Rhinometry and
Rhinomanometry. Otolaryngol Head Neck Surg 2003; 128:
510-516.
Wang DY
Managing allergic rhinitis in primary care clinics. Medical Tribune;
2003: 8.
Yang L, Cheong N, Wang DY, Lee BW, Kuo IC, Huang CH, Chua KY
Generation of monoclonal antibodies against Blo t 3 using DNA
immunization with in vivo electroporation. Clin Exp Allergy 2003;
33: 663-668.
Teaching in the OR
72
Faculty of Medicine Research Report 2003
Chan KO, Huang ZL, Wang DY
Acoustic rhinometric assessment of nasal obstruction after
treatment with fluticasone propionate in patients with perennial
rhinitis. Auris Nasus Larynx 2003; 30: 379-83.
Yeoh SM, Kuo IC, Wang DY, Liam CK, Sam CK, De Bruyne JA, Lee BW,
Cheong N, Chua KY
Sensitization profiles of Malaysian and Singaporean subjects to
allergens from Dermatophagoides pteronyssinus and Blomia
tropicalis. Int Arch Allergy Immunol. 2003; 132: 215-220.
Chao S S, K S Loh, Luke Tan
Modalities of surveillance in treated nasopharyngeal carcinoma.
Otolaryngol Head Neck Surg. 2003; 129: 61-64.
Staff Profile
Associate Professor & Head
Clinical Professor
Visiting Professors
:
:
:
Assistant Professors
:
Senior Research Scientists
:
Tan Kim Siang, Luke
Yeoh Kian Hian
Peter Alberti
James D Smith
Alan G Kerr
Thomas Loh
Lynne Lim
Chao Siew Shuen
Ruan Run Sheng
Wang De Yun
Contact Information
Contact Person
:
Telephone
Facsimile
Email
Postal Address
:
:
:
:
Contact Person
:
Telephone
Email
:
:
Dr Wang De Yun
Senior Research Scientist
6772-5373 / 6772-5370
6775-3820
entwdy@nus.edu.sg
Department of Otolaryngology
National University of
Singapore
5 Lower Kent Ridge Road
Singapore 119074
Assoc Prof Tan Kim Siang Luke
Head of Department
6772-5370
entsec@nus.edu.sg
Faculty of Medicine Research Report 2003
73
INTRODUCTION
Research in the Department of Paediatrics is focused on three major
areas: Human Genetics, Immunology and Allergy, and Paediatric Oncology.
The Human Genetics Research Group aims to establish and develop
genetic research and diagnostic facilities in cardiovascular, endocrine
(adrenal disease and obesity), neuromuscular, neurometabolic,
haematology-oncology, hepatobiliary, renal and pulmonary genetics.
The Immunology and Allergy Research Group has 2 major laboratories:
The Pediatric Allergy Laboratory main areas of focus include
the immunopathogenesis of asthma and allergic diseases;
the prevention and treatment of asthma and allergic diseases,
specifically the optimization of DNA vaccines for allergic diseases;
the study of immunoregulatory proteins and their application in
treatment of allergic diseases; and characterization of Blomia
tropicalis mite allergens.
The Pediatric Renal and Transplant Immunology Research Laboratory
main areas of focus include the immunopathogenesis of nephrotic
syndrome, in particular minimal change disease; the immunogenetics
of familial nephritis; identification and characterization of the
immunosuppressive effects of Chinese medication used to treat
glomerulonephritis; and infections in solid organ transplantation.
The Pediatric Oncology Research Group has as its main focus
research in childhood acute lymphoblastic leukemia, with emphasis on
the identification of profiles based on gene expression and proteomic
analysis in pre- and post-therapy leukaemic blasts, that could be applied
to improving diagnosis and prognostication of childhood acute
lymphoblastic leukemia.
DEPARTMENT OF
Paediatrics
RESEARCH HIGHLIGHTS
Summary
The Human Genetics Research Group has achieved the following:
Discovered novel gene mutations associated with severe obesity in
their study which included over 200 subjects in an effort to determine
the obesity genes, phenotypes and complications profile of obese
children in Singapore. The group has published the world’s first report
of a novel melanocortin 3 receptor gene (MC3R) mutation associated
with severe obesity (Journal of Clinical Endocrinology and Metabolism
2002; 87(3):1423-1426).
Developed a comprehensive and multiplex method to detect mutations
in the alpha-thalassemia and beta-thalassemia genes, a process which
has wide clinical applications in our population where the mutations
are highly prevalent. Important publications arising from this work
include Clinical Chemistry 2003; 49:209-218; 49:800-803.
74
Faculty of Medicine Research Report 2003
Completed analysis of the dystrophin gene in 3 Asian populations,
resulting in the development of mutation screening strategies for
rapid molecular diagnosis. The results of this work has been published
in Hum Genet 2002; 47:552-555.
The multidisciplinary team working with the Biosensor Focused Interest
Group (BFIG), developed 2 new micro-devices for automated DNA
extraction and amplification on a microfluidic chip. The team pioneered
state-of-the-art integration of microfluidic systems and developed
novel components for fluidic mixing, blood cell sorting, blood cell
lysis and binding of nucleic acids to a surface for DNA purification.
This has wide commercial applications in molecular diagnostic
laboratories. The two chips have been licensed to a company
for marketing.
C13
A
C13
C18
C21
The Pediatric Immunology and Allergy Group has achieved the following:
A. Pediatric Allergy Laboratory
Development of a murine model for allergic dermatitis and asthma
using mite allergens such as Der p1, Der p2 and Blot 5. One of the
important characteristic features of this model is that sensitized
animals developed both allergic and neurogenic lung and cutaneous
inflammations, and has been accepted in a major journal (J Invest
Dermatol 2003, Aug;121(2):289-93).
The Allergy Group is one of the leading groups in the world working
on Blomia tropicalis allergens, and has developed 6 patents from this
work. The recombinant and native forms of at least 10 Blomia tropicalis
allergens cloned by the group are being evaluated clinically.
Industrial collaboration with GlaxoSmithKline Biologicals, s.a. Belgium,
to work on the optimization of DNA vaccines for allergic diseases.
Functional and structural studies of the Fip-fve protein, an
immunomodulatory protein isolated from mushroom Flammulina
velutipes, have shown that Fve is a potent adjuvant/immunomodulator
that enhances the efficacy of immunotherapy for allergy related
asthma and rhinitis. The novel aspects of this study will be
patented by NUS and GIS in April 2004.
B. Pediatric Renal and Transplant Immunology Laboratory
The Group has identified a new molecule, PX-3.102, from a
Chinese herb CMX-13, which is 1000-fold more potent in its
in-vitro immunosuppressive activity (US provisional patents serial
no.60/205,821 and 60/209,557). We currently have a licensing
agreement with Pan Pacific Pharmaceuticals (New Jersey, NY) for
further clinical development of PX-3.102, taking it into preclinical
toxicity studies and phase I clinical trials.
The Pediatric Oncology Group has achieved the following:
Published their highly successful work in gene expression profiling in
childhood acute lymphoblastic leukemia and population pharmacogenetic
study in thiopurine methyltransferase enzymes. The group has received
several local and international awards for the biodiscovery and
development of DNA and proteomic diagnostic biochips in childhood
acute lymphoblastic leukemia, including the prestigious Asian Innovation
Award for 2003.
Faculty of Medicine Research Report 2003
75
C16
C
N
C3
B
C3
C10
C6
N
C
Figure- The molecular models of Blo t1 (A)
and Der p1 (B) ,ite allergens. The conserved
cysteine residues forming putative
disulphate linkage as well as the active site
cysteine are shown. The N- and C-terminals
are indicated in both structures
DEPARTMENT OF
Paediatrics
The incidence and consequence of the Gly71Arg polymorphism
in the human UDP-glucuronosyl-transferase 1A1 (UDP1A1) in the
term newborn population - A prospective study
Project Description
Principal Investigator
Grants Awarded in 2003
: Dr Denise Goh Li Meng
BioMEMS for cells characterization
Environmental endotoxin exposure and its relationship with atopy
and allergy symptoms in the first two years
Principal Investigator
Co-Principal Investigator
Principal Investigator
Collaborators
Establishment and Validation of a preimplantation genetic
diagnosis program in Singapore
: Prof Hugo van Bever
: Dr Dawn Lim,
Adj Assoc Prof Lee Bee Wah,
Assoc Prof Chua Kaw Yan,
Ms Tan Teng Nging,
Assoc Prof Ho Bow,
Prof Karnen Garna Baratwidjaja
(Medicine, University of Indonesia)
Principal Investigator
Co-Principal Investigator
: Assoc Prof Poenar Daniel Piu (NTU)
: Dr Heng Chew Kiat
: Assoc Prof Samuel Chong
: Dr Christine Yap (SGH)
To establish values for cellular components in bronchoalveolar
lavage fluid as well as intracellular and extracellular IL-1ß, IL-6,
IL-10, tumour necrosis factor and gamma-interferon levels in
lung fluid obtained by bronchoscopic and non-bronchoscopic
methods from patients with pneumonia requiring bronchoscopy
for clearance of secretions
Principal Investigator
Collaborators
: Dr Nicola Ngiam Siew Pei
: Assoc Prof Daniel Goh Yam Thiam,
Dr Cindy Hia (NUH)
The role of myocardial perfusion imaging in the detection of
cardiac complications in Kawasaki disease
Principal Investigator
Collaborators
: Assoc Prof Quek Swee Chye
: Dr Ho Kheng Thye (NUH),
Dr Terence Lim (NUH)
Characterization and evaluation of the functional significance of
the unpregulated DEC-1 gene in children with steriod-responsive
nephrotic syndrome (SRNS) in relapse
Principal Investigator
Collaborators
: Prof Yap Hui Kim
: Dr Caroline Lee Guat Lay,
Dr Gong Wei Kin,
Mr Wilson Cheung Wai
Molecular Basis of Nonsense-mediated mRNA decay (NMD) in
beta thalassemia
Principal Investigator
Co-Principal Investigator
Collaborator
: Assoc Prof Samuel Chong
: Dr Denise Goh Li Meng
: Dr Caroline Lee Guat Lay
Development of prophylactic and therapeutic vaccines for asthma
and allergic diseases
Prevalence of Allergic symptoms and Atopy in 2 diverse populations
in SE Asia, and a comparative evaluation of the influence of
environmental microbial factors
Principal Investigator
Collaborators
Multiplex SNaPshotTM assay for common B-globin gene mutations. Shown are
Genescan electropherograms from a normal individual (A) and a B-thalassemia
patient compound heterozygous for two common mutations (B). The mutations
sites screened by this panel are indicated on the X-axis. At each mutation site,
the peak color specifies the allele/hucleotide, such that a mutant allele displays
a characteristics peak color and off-shifted position relative to its normal
allele peak
: Prof Hugo van Bever
: Dr Dawn Lim,
Adj Assoc Prof Lee Bee Wah,
Assoc Prof Chua Kaw Yan,
Ms Tan Teng Nging,
Assoc Prof Ho Bow,
Assoc Prof Malkeet Singh,
Prof Karnen Garna Baratwidjaja
(Medicine, University of Indonesia)
76
Principal Investigator
Collaborators
: Assoc Prof Chua Kaw Yan
: Adj Assoc Prof Lee Bee Wah,
Dr Ranee Lim,
Dr Lynette Shek,
Assoc Prof Daniel Goh Yam Thiam,
Dr Cheong Nge,
Dr Denise Goh Li Meng,
Dr Liew Lip Nyin,
Dr Dawn Lim,
Dr Thomas August (John Hopkins),
Dr Sven Pettersson (Bengt Bjorksten –
Karolinska Inst. Sweden),
Assoc Prof Lee Yuan Kuan,
Dr Lu Jinhua,
Dr Wang De Yun
Faculty of Medicine Research Report 2003
Characterisation of CYP11B1 mutations in 11-beta
hydroxylase deficiency
Principal Investigator
: Assoc Prof Loke Kah Yin
Biodiscovery and Development of DNA and proteomic diagnostic
biochips in Childhood Acute Lymphoblastic Leukaemia – NUS
Young Investigator’s Award
Principal Investigator
Hepatitis B Immune Status in children - a decade after
mass vaccination
Principal Investigator
Collaborators
: Assoc Prof Quak Seng Hock
: Dr Lai Poh San,
Dr Marion Aw,
Dr Oh Meng Choo
Immune responses to allergens in early childhood in relation to
environmental factors
Principal Investigator
Collaborators
Targeted gene repair of Duchenne Muscular Dystrophy
Lymphoblastoid Cells using modified oligonucleotide
Principal Investigator
Collaborators
: Dr ZA Dwi Pamono
: Dr Lai Poh San,
Dr Yee Woon Chee,
Dr Feng Zhiwei (NUH)
Ongoing Projects
: Dr Allen Yeoh Eng Juh
: Assoc Prof Chua Kaw Yan
: Adj Assoc Prof Lee Bee Wah,
Assoc Prof Lee Yuan Kun,
Assoc Prof Ho Bow,
Dr Shek Pei Chi, Lynette,
Prof Bengt Bjorksten,
Dr Scott M Montgomery
Functional studies of mutant melanocortin receptors due to novel
mutations of the melanocortin-3 receptor gene and melanocortin4 receptor gene causing obesity in humans
Principal Investigator
Collaborator
: Dr Lee Yung Seng
: Assoc Prof Loke Kah Yin
Characterization of differentially expressed genes from CD8+ Th2
cells in children with idiopathic nephrotic syndrome in relapse
and remission
Retroviral-mediated strategies for in vivo expression reporting
and isolation of novel zebrafish genes important in human
development and disease
Principal Investigator
Co-Principal Investigators
Principal Investigator
: Prof Yap Hui Kim
: Dr Cheung Wai, Wilson,
Dr Caroline Lee Guat Lay
Production of codon optimized recombinant dust mite
allergens in Chinese hamster ovary cells for diagnostic and
therapeutic purposes
Principal Investigator
Collaborators
: Assoc Prof Chua Kaw Yan
: Dr Ranee Lim Lay Hong,
Dr Dawn Lim Li Chern,
Dr Cheong Nge
An evaluation of cystic fibrosis transmembrane conductace
regulator (CFTR) gene mutations in Asians with chronic
pulmonary disease
Principal Investigator
Co-Principal Investigator
Collaborators
: Assoc Prof Daniel Goh Yam Thiam
: Assoc Prof Samuel Chong
: Dr Nicola Ngiam Siew Pei,
Assoc Prof Lim Tow Keang,
Dr Azman Johan (AH),
Dr Ong Kian Chung (TTSH),
Dr Chng Seo Yi,
Dr Cindy Hia Ping Ping,
Dr Shek Pei Chi, Lynette
Evaluation of the allergenicity of commonly consumed tropical
fish and characterization of their novel allergens
Principal Investigator
Collaborators
Characterization of the mechanism of albumin permeability in
childhood minimal change nephrotic syndrome
Principal Investigator
Collaborator
: Prof Yap Hui Kim
: Assoc Prof Hanry Yu
Single nucleotide polymorphisms (SNPS) in the MDR1 Gene in
the three ethnic groups in Singapore – correlating
polymorphisms/haplotypes with drug transport in search of
functional SNPS
Principal Investigator
Co-Principal Investigator
Collaborator
: Assoc Prof Samuel Chong
: Dr Caroline Lee Guat Lay
: Prof Edmund Lee
Production of recombinant chimeric mite allergens for
specific immunotherapy
Principal Investigator
Collaborators
: Dr Liew Lip Nyin
: Assoc Prof Chua Kaw Yan,
Dr Dawn Lim Li Chern
Heterologous expression of dust mite allergens in
lactobacillus casei
Principal Investigator
Collaborators
: Dr Dawn Lim Li Chern
: Dr Shek Pei Chi, Lynette,
Ms Yi Fong Cheng,
Adj Assoc Prof Lee Bee Wah
Faculty of Medicine Research Report 2003
: Assoc Prof Samuel Chong
77
: Dr Ranee Lim Lay Hong
: Assoc Prof Chua Kaw Yan,
Assoc Prof Lee Yuan Kun
Molecular characterization of mutant DAX-1 protein in X-linked
adrenal hypoplasia congenita: A study of 3 novel mutations
An arrayed-based primer extension assay for genotyping of SouthEast Asian thalassaemia mutations
Principal Investigator
Collaborator
Principal Investigator
Collaborator
: Assoc Prof Loke Kah Yin
: Dr John C Achermann
Characterization of molecular events involved in the
immunosuppressive action of PX-3.102 – a bioactive extract from
a Chinese herb
Principal Investigator
Collaborators
: Prof Yap Hui Kim
: Dr Caroline Lee Guat Lay,
Assoc Prof Ang Siau Gek,
Assoc Prof Lai Yee Hing
A nation-wide study in childhood acute lymphoblastic leukemia
incorporating minimal residual disease based risk-stratification
pharmacogenomic study of thiopurine methyltransferase deficiency
and establishment of a cell bank
Principal Investigator
Collaborators
Influence of probiotics on atopy, atopic disease and immunological
responses – A randomised double-blind, placebo-controlled
clinical trial
Principal Investigator
Collaborators
: Dr Shek Pei-Chi, Lynette
: Dr Marion Margaret Aw,
Adj Assoc Prof Lee Bee Wah,
Assoc Prof Abu Rauff,
Dr Chong Yap Seng,
Dr Saw Seang Mei,
Dr Dawn Lim Li Chern,
Assoc Prof Lee Yuan Kun,
Assoc Prof Chua Kaw Yan,
Dr Steven Ng Chin Yuen
: Assoc Prof Quak Seng Hock
: Dr Lai Poh San,
Dr Marion Margaret Aw
Refining the molecular diagnostics for routine screening in
Duchenne and Becker muscular dystrophy through analysis of
protein truncating mutations
Principal Investigator
Collaborators
: Prof Low Poh Sim
: Dr Lai Poh San,
Dr Stacey Tay
Principal Investigator
Co-Principal Investigator
Collaborators
: Dr Lee Yung Seng
: Assoc Prof Loke Kah Yin
: Dr Saw Seang Mei,
Dr Rose Vaithinathan
(School Health Service, HBP)
Characterizing normative values for calcaneal broadband
ultrasound attenuation (BUA) in Singapore children and
adolescents. Towards an accurate assessment of bone strength
and fracture risk in chronic paediatric disease
Principal Investigator
Co-Principal Investigator
Collaborators
: Dr Lee Yung Seng
: Assoc Prof Loke Kah Yin
: Dr Saw Seang Mei,
Assoc Prof James Goh
Standardization of hyperventilation activation on EEG recording
in children using non-invasive end-tidal carbon dioxide monitoring,
and the evaluation of the threshold value for activating absence
seizures in childhood absence epilepsy
Development of an micro-DNA extractor
Principal Investigator
Co-Principal Investigator
Collaborators
: Dr Allen Yeoh Eng Juh
: Assoc Prof Quah Thuan Chong,
Dr Tan Poh Lin,
Dr Tan Ah Moh (KKH),
Dr Heng Chew Kiat,
Dr Li Chi Kong
(Chinese University of Hong Kong),
Dr Dario Campana
(St Jude Children’s Research Hospital,
Memphis, US),
Dr Pui Ching Hon
(St Jude Children’s Research Hospital,
Memphis, US)
Characterisation of the genetics and complications of childhood
obesity in Singapore
Molecular analysis of JAG1 gene in biliary atresia, paediatric liver
disease and Allagille syndrome
Principal Investigator
Collaborators
: Dr Allen Yeoh Eng Juh
: Assoc Prof Quah Thuan Chong
: Dr Victor Samper (IME)
: Dr Heng Chew Kiat
: Assoc Prof Lim Tit Meng,
Dr Chen Yu (IME),
Dr Pavel Neuzil (IME),
Dr Daniel Poenar (NTU)
Principal Investigator
Collaborators
: Dr Ong Hian Tat (NUH)
: Prof Low Poh Sim,
Dr Stacey Tay Kiat Hong,
Ms Karen Lim Joo Li
Genetic polymorphisms of the IL-13 gene and IL-13 receptor
complex genes in minimal change nephrotic syndrome of childhood
Development of diagnostic and therapeutic tools for asthma and
allergic disease
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Prof Yap Hui Kim
: Assoc Prof Samuel Chong,
Mr Cheung Wei Wilson
78
: Adj Assoc Prof Lee Bee Wah
: Dr Chua Kaw Yan,
Assoc Prof Daniel Goh Yam Thiam,
Dr Lynette Shek,
Dr Chew Fook Tim,
Dr Wang De Yun
Faculty of Medicine Research Report 2003
Novel genetic variation screening in the newly cloned Acyl
Coenzyme A: Cholesterol Acyltransferase 2 (ACAT2) gene in the
3 ethnic groups of Singapore and their impact on plasma lipid
factors in relation to coronary artery disease
Role of IL-13 as a modulator of monocyte production of a vascular
permeability factors in idiopathic nephrotic syndrome of childhood
Principal Investigator
Collaborators
Drug resistant cytomegalovirus mutant strains in organ
transplant recipients
: Dr Heng Chew Kiat
: Dr Yang Hong Yuan,
Dr Stephen Sturley
(Institute of Human Nutrition,
Columbia University, USA),
Prof Richard Deckelbaum
(Institute of Human Nutrition,
Columbia University, USA),
Assoc Prof Samuel Chong,
Adj Prof Nilmani Saha, (Dept of Human
Genetics University of Pittsburgh, USA),
Prof Low Poh Sim
DNA vaccine for allergic asthma – Study of mechanisms and
optimization of gene transfer using cDNA encoding for a major
mite allergen, Der p 1
Principal Investigator
Collaborator
: Dr Liew Lip Nyin
: Assoc Prof Chua Kaw Yan
IL-13-induced monocyte 12/15-lipoxgenase gene activation:
A novel pathogenetic pathway for induction of minimal change
nephrotic syndrome
Principal Investigator
Collaborators
: Prof Yap Hui Kim
: Assoc Prof Khoo Hoon Eng,
Assoc Prof Ang Siau Gek,
Assoc Prof Lee Hian Kee,
Dr Gilbert SC Chiang (SGH)
Principal Investigator
Principal Investigator
Collaborators
: Prof Yap Hui Kim
: Prof Yap Hui Kim
: Dr Marion Aw,
Dr Chan Kwai Peng,
Dr Gamini Kumarasinghe
Evaluation of the prevalence and factors associated with snoring
and obstructive sleep apnea (OSA) in children in Singapore
Principal Investigator
Co-Principal Investigator
: Assoc Prof Daniel Goh Yam Thiam
: Dr Chng Seo Yi
Relationship between Exhaled Nitric Oxide and Atopy in Asthmatic
and Non-Asthmatic Asian Adults
Principal Investigator
Co-Principal Investigator
: Assoc Prof Daniel Goh Yam Thiam
: Dr Chng Seo Yi
A study on Haplotype Structure and SNP frequencies in candidate
genes in neurological disease and drug response
Principal Investigator
Co-Principal Investigators
: Prof Simon Shorvon
: Prof Nicholas Wood,
Prof David Goldstein,
Prof Kua Ee Heok,
Dr Yee Woon Chee,
Assoc Prof Lee Wei Ling,
Dr Lai Poh San
Simplified molecular diagnostic testing for Fragile X mental
retardation syndrome
Molecular characterization of adult onset multiple acyl coA
dehydrogenase deficiency (MADD)
Principal Investigator
Principal Investigator
Co-Principal Investigator
: Assoc Prof Samuel Chong
Study of the immunopathogenesis and neurogenic inflammation
of atopic dermatitis
Principal Investigator
: Assoc Prof Chua Kaw Yan
Molecular genetics in neuromuscular disorders
Principal Investigator
Co-Principal Investigators
Characterising normative values for areal and volumetric bone
mineral density and body composition in Singapore children and
adolescents: towards an accurate assessment of therapeutic
intervention in chronic paediatric disease and childhood obesity
Principal Investigator
Collaborators
: Assoc Prof Loke Kah Yin
: Dr Lee Yung Seng,
Assoc Prof James Goh,
Assoc Prof Saw Seang Mei
Molecular analysis and genotype-phenotype correlations for
the mitochondrial disorders in Singapore: A study of the
pathogenesis, as the first step to early diagnosis and possible
treatment intervention
Principal Investigator
Collaborators
: Dr Yee Woon Chee
: Dr Ho Meng Fatt,
Dr Lai Poh San
International Publications
Aw M M, R M Taylor, A Verma, A Parke, A J Baker, D Hadzic, P Muiesan,
M Rela, N D Heaton, G Mieli-Vergani and A Dhawan
Basiliximab (Simulect) for the treatment of steroid resistance
rejection in pediatric liver transplant recipients : a preliminary
experience. Transplantation, 75, (6) (2003): 796-799.
: Dr Stacey Tay Kiat Hong
: Assoc Prof Loke Kah Yin,
Dr Lee Yung Seng
Faculty of Medicine Research Report 2003
: Dr Lai Poh San
: Dr Yee Woon Chee
79
Chen S P, W Cheung, C K Heng, S C Jordan and H K Yap
Kuo I, N Cheong, M Trakultivakorn, B W Lee and K Y Chua
Childhood nephrotic syndrome in relapse is associated with downregulation of monocyte CD14 expression and lipopolysaccharideinduced tumour necrosis factor-%%alpha%% production. Clinical
and Experimental Immunology, 134 (2003): 111-119.
An extensive study of human IgE cross-reactivity of Blo t 5 and
Der p 5. Journal of Allergy and Clinical Immunology, 111, (3)
(2003): 603-609.
Lee Y S, A M Elliott, K Y Loke and R S Lachman
Cheong N, S C Soon, J D Ramos, I Kuo, K R Prasanna, B W Lee and
K Y Chua
Lack of human IgE cross-reactivity between mite allergens Blo
t 1 and Der p 1. Allergy, 58 (2003): 912-920.
A distinctive type of Metaphyseal Chondrodysplasia with
characteristic thickening of the distal ulna and radius: possible
Metaphyseal Chondrodysplasia-Rosenberg. American Journal of
Medical Genetics, 119A (2003): 50-56.
Cheong N, L Yang, B W Lee and K Y Chua
Li H, W Cheung, H H CHOO, J H P CHAN, P S Lai and W S F Wong
Cloning of a group 3 allergen from Blomia tropicalis mites. Allergy,
58, (4) (2003): 352-356.
IL-10 synergistically enhances GM-CSF-induced CCR1 expression
in myelomonocytic cells. Biochemical and Biophysical Research
Communications, 304 (2003): 417-424.
Cheung M, S Bansal, M M Aw, C R Buchanan, G Mieli-Vergani and
A Dhawan
Lim J, Lal S, Ng KC, Ng KS, Saha N, Heng CK
Liver failure in a neonate with congenital adrenal
hyporesponsiveness (Letter to editor). European Journal of
Pediatrics, 162, (7-8) (2003): 558.
Variation of the platelet glycoprotein IIIa PIA1/A2 allele
requencies in the three ethnic groups of Singapore. Int J Cardiol
90:269-273.
Chew J L and K Y Chua
Miao Y, Chong CS, Chai Y, Chen Y, Zou Q; Yan T; Heng CK, Lim TM
Collection of mouse urine for bioassays. Laboratory Animals, 32,
(6) (2003): 1-3.
Flip-chip packaged micro-plate for low cost thermal multiplexing.
Int J Comp Engr Sci (in press).
Chew J L, C B Wolfowicz, H Q Mao, K W Leong and K Y Chua
Miao Y, Chen Y, Zou Q, Singh J, Yan T; Heng CK, Lim TM
Chitosan nanoparticles containing plasmid DNA encoding house
dust mite allergen, Der p 1 for oral vaccination in mice. Vaccine,
21 (2003): 2720-2729.
Low cost micro-PCR array and micro-fluidic integration on single
silicon chip. Int J Comp Engr Sci (in press).
Duan W, I Kuo, S Selvarajan, K Y Chua, B H Bay and W S F Wong
Mitry R R, R D Hughes, M M Aw, C Terry, G Mieli-Vergani, R Girlanda, P
Muiesan, M Rela, N D Heaton and A Dhawan
Antiinflammatory effects of genistein, a tyrosine kinase inhibitor,
on a guinea pig model of asthma. American Journal of Respiratory
& Critical Care Medicine, 167, (2) (2003): 185-192.
Human hepatocyte isolation and relationship of cell viability to
early graft function. Cell Transplantation, 12 (2003): 69-74.
Ng B L, S H Quak, M M Aw, K T Goh and B Ho
Gwee P C, K Tang, J M Z Chua, E J D Lee, S S Chong and C G L Lee
Simultaneous genotyping of seven single nucleotide
polymorphisms (SNPs) of the MDR1 gene by single-tube multiplex
minisequencing. Clinical Chemistry, 49 (2003): 672-676.
Immune responses to differentiated forms of Helicobacter pylori
in children with epigastric pain. Clinical and Diagnostic Laboratory
Immunology, 10, no. 5 (2003): 866-869.
Ramirez S P B, T T Durai and S I HSU
Huang C H, I Kuo, H Xu, Y S Lee and K Y Chua
Mite allergen induces allergic dermatitis with concomitant
neurogenic inflammation in mouse. Journal of Investigative
Dermatology, 121 (2003): 289-293.
Paradigms of public-private partnerships in end-stage renal
disease care: The National Kidney Foundation Singapore.
Kidney International, Supplement 83, 63 (2003): S101-S107.
Ramirez S P B, S I HSU and W McClellan
Kadam-Pai P, X Y Su, J J Miranda, A Soemantri, N Saha, C K Heng and
P S Lai
Ethnic variations of a retinoblastoma susceptibility gene
polymorphism in 8 Asian populations. Journal of Genetics, 82,
nos. 1 & 2 (2003): 33-37.
Koh E G, K Lam, A Christoffels, M V Erdmann, S Brenner and V Byrappa
Hox gene clusters in the Indonesian coelacanth, Latimeria
menadoensis. Proceedings of the National Academy of Sciences
of the United States of America, 100, (3) (2003): 1084-1088.
80
Taking a public health approach to the prevention of end-stage
renal disease: The NKF Singapore Program. Kidney International,
Supplement 83, 63 (2003): S61-S65.
Ramos J D A, N Cheong, B W Lee and K Y Chua
Peptide mapping of immunoglobulin E and immunoglobulin G
immunodominant epitopes of an allergenic Blomia tropicalis
paramyosin, Blo t 11. Clinical and Experimental Allergy, 33, (4)
(2003): 511-517.
Faculty of Medicine Research Report 2003
Ramos J D A, A S M Teo, K L Ou, L C Tsai, B W Lee, N Cheong and
K Y Chua
Comparative allergenicity studies of native and recombinant
Blomia tropicalis paramyosin (Blo t 11). Allergy, 58 (2003):
412-419.
Wang W, K Y Wee-Kham, G H Yeo, T C Quah and S S Chong
Multiplex-minisequencing screen for common Southeast Asian
and Indian beta-thalassemia mutations. Clinical Chemistry, 49,
(2) (2003): 209-218.
Seow S V, I Kuo, P Paaventhan, P R Kolatkar and K Y Chua
Weale M E, C Depondt, S J Macdonald, A Smith, P S Lai, S D Shorvon,
N W Wood and D B Goldstein
Crystallization and Preliminary X-ray Crystallographic Studies on
the Fungal Immunomodulatory Protein Fve from the Golden
Needle Mushroom (Flammulina velutipes). Acta Crystallographica
Section B - Structural Science, 159 (2003): 1487-1489.
Selection and evaluation of haplotype tagging SNPs in the neuronal
sodium channel gene SCN1A: implications for linkage
disequilibrium gene mapping. American Journal of Human
Genetics, 73 (2003): 551-565.
Shek LP, Lee BW
Wolfowicz C B, T HuangFu and K Y Chua
Epidemiology and seasonality of respiratory tract virus infections
in the tropics. Paediatr Respir Rev 2003; 4:105-11.
Expression and immunogenicity of the major house dust mite
allergen Der p 1 following DNA immunization. Vaccine, 21, (1112) (2003): 1195-1204.
Shek LP, Khor ES, Tan GH, et al
Comparative study of the reactogenicity of a three-component
acellular pertussis vaccine and whole-cell pertussis vaccine
administered to healthy Singaporean infants. Southeast Asian J
Trop Med Public Health 2003; 34:863-8.
Wong G Q, M DiPietro, K Roeder, C K Heng, C H Bunker and R F Hamman
Tan H H, P S Low, Y S Tan, M C Tong, N Saha, H Yang and C K Heng
Wong M N L, C R Kirk and S C Quek
ABCA1 gene polymorphisms and their associations with Coronary
Artery Disease and Plasma Lipids in males from 3 ethnic
populations in Singapore. Human Genetics, 113, (2) (2003): 106117.
Persistent truncus arteriosus with absence of right pulmonary
artery. Heart, 89 (2003): 549.
Tham CK, W.C Chin, Heng CK
Predicting risk of coronary artery disease from DNA microarraybased genotyping using neural networks and other statistical
analysis tools. J Bioinformatics Comp Biol 1:521-539.
Van Bever H P, C P P Hia and S C Quek
Childhood SARS in Singapore (Letter to editor). Archives of
Diseases in Childhood, 88 (2003): 742.
Cladistic analysis of human apolipoprotein A4 polymorphisms in
relation to quantitative plasma lipid risk factors of coronary heart
disease. Annals of Human Genetics, 67, (2) (2003): 107-124.
Wong S C, E Oh, C H Ng and K P Lam
Impaired germinal center formation and recall T-cell-dependent
immune responses in mice lacking the costimulatory ligand B7H2. Blood, 102, (4) (2003): 1381-1388.
Yang L, N Cheong, D Y Wang, B W Lee, I Kuo, C H Huang and K Y Chua
Generation of monoclonal antibodies against Blo t 3 using
DNA immunization with in vivo electroporation. Clinical
and Experimental
Yap W H, A Tay, S Brenner and V Byrappa
Wang D Y, D Y T Goh, A K L Ho, F T Chew, K H Yeoh and B W Lee
The upper and lower respiratory responses to nasal challenge
with house-dust mite blomia tropicalis. Allergy, 58, (1) (2003):
78-82.
Molecular cloning of the pufferfish (Takifugu rubripes) Mx gene
and functional characterization of its promoter. Immunogenetics,
54, (10) (2003): 705-713.
Yeoh S C, E Lee, B W Lee and D L M Goh
Wang GQ, DiPetro M, Roeder K, Heng CK, Bunker CH, Hamman RF,
Kamboh MI
Cladistic analysis of human apolipoprotein A4 polymorphisms in
relation to quantitative plasma lipid risk factors of coronary heart
disease. Ann Hum Genet 67:107-124.
Wang W, E S K Ma, A Y Y Chan, D H K Chui and S S Chong
Multiplex-minisequencing screen for seven Southeast Asian nondeletional alpha-thalassemia mutations. Clinical Chemistry, 49
(2003): 800-803.
Wang W, E S K Ma, A Y Y Chan, J Prior, W N Erber, L C Chan, D H K Chui
and S S Chong
Single-tube multiplex-PCR screen for anti-3.7 and anti-4.2 alphaglobin gene triplications. Clinical Chemistry, 49 (2003): 16791682.
Faculty of Medicine Research Report 2003
Severe acute respiratory syndrome : Private hospital in Singapore
took effective control measures (Letter to editor). British Medical
Journal, 326, (7403) (2003): 1394.
Yu W P, S Brenner and V Byrappa
Duplication, degeneration and subfunctionalization of the nested
synapsin-Timp genes in Fugu. Trends in Genetics, 19, (4) (2003):
180-183.
Zhang T, T H Tan, J Fu, Y Ning, F R Jirik, S Brenner and V Byrappa
The regulation of retina specific expression of rhodopsin gene in
vertebrates. Gene, 313 (2003): 189-200.
Zhang Q, Chieu HK, Low CP, Zhang SC, Heng CK, Yang HY
Schizosaccharomyces pombe cells deficient in triacylglycerols
synthesis undergo apoptosis upon entry into stationary phase.
J Biol Chem 278 : 47145 – 47155.
81
Contact Information
Staff Profile
Associate Professor & Head
Senior Professorial Fellow
Professors
:
:
:
Associate Professors
:
Research Associate Professors
:
Adjunct Associate Professors
:
Assistant Professors
:
Senior Research Fellows
:
Research Fellows
:
Adjunct Senior Researcher
Adjunct Senior Fellow
Adjunct Research Fellow
Research Assistants
:
:
:
:
Quak Seng Hock
Emeritus Prof Wong Hock Boon
Yap Hui Kim
Low Poh Sim
Hugo PS van Bever
Roy Joseph
Quah Thuan Chong
Loke Kah Yin
Quek Swee Chye
Daniel Goh Yam Thiam
Chua Kaw Yan
Samuel Chong Siong Chuan
Byrappa Venkatesh
Lee Bee Wah
Lee Wei Ling
William Yip Chin Ling
Subramaniam Sivasankaran
Yip Yeng Loong
Marion Margaret Aw Hui Yong
Denise Goh Li Meng
Stacey Tay Kiat Hong
Lynette Shek Pei Chi
Lee Yung Seng
Nicola Ngiam Siew Pei
Allen Yeoh Eng Juh
Dawn Lim Li Chern
Zubair Amin
Lai Poh San
Heng Chew Kiat
Cong Lin
Huang Chiung Hui
Kuo I-chun
Lewin-Koh, Nicholas John I
Liew Lip Nyin
Lim Lay Hong, Ranee
Narasimhan Kothandaraman
Seow See Voon
Tan Teng Nging
Wei Chang Li
Wang Gang
Sylvia Ramirez Paz Baens
Lam Kong Peng
Yeo Chao Chuang, Adrian
Cheah Siew Hong, Felicia
Dolendo Mae Concepcion
Lye Hui Jen
Lesaicherre, Marie-laure
Lim Chin Chin
Liu Rubing
Ng Puay Guan, Tony
Sharmila Adhikari
Tan Petrina
Tan Teng Nging
Xu Hui
Yi Fong Cheng
82
Contact Person
:
Telephone
Facsimile
Email
Postal Address
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Homepage
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Faculty of Medicine Research Report 2003
Prof Yap Hui Kim
Director of Research,
Paediatrics
6772-4112
6779-7486
paeyaphk@nus.edu.sg
Department of Paediatrics
National University of
Singapore
Lower Kent Ridge Road
Singapore 119074
www.med.nus.edu.sg/paed
INTRODUCTION
Research remains a major focus in the Department of Pathology with
12 research grants led by Principal Investigators from the Department.
Our traditional strength has been the morphological and
immunohistochemical analysis of tissue, specifically tumour tissue. Even
as we continue to capitalize on this as well as the vast archival tissue
at our disposal, we have also adopted a more multidisciplinary approach
to our tumour research. This includes the use of molecular techniques
(genomics, proteomics and molecular cytogenetics) as clinical molecular
research tools to build up on the strong histopathological expertise of
the Department.
Translational Research at the Pathology Department
- Tissue Microarrays, FISH, TCR Gene Rearrangements
and Gene Sequencing
Areas of research include the study of genetic mutations/alterations in
different tumours, construction of tissue arrays/molecular information
arrays for different tumours, characterization of various malignancies
applying traditional immunohistochemical techniques, assessing lymphoid
malignancies using FISH probes, the analysis of DNA ploidy and apoptosis
in malignant tissues and the study of emergent pathogens such as the
SARS coronavirus and dengue virus. We have also developed strong links
with research institutes such as ORI and GIS. Collaborative projects
include studies on angiogenesis in tumours, evaluation of various forms
of therapy for chronic hepatitis B infection, pathogenesis of gastric
mucosal injury in Helicobacter infections and gastric cancer and the
development of chitin-based materials for tissue engineering.
Faculty of Medicine Research Report 2003
83
DEPARTMENT OF
Pathology
To develop and evaluate diagnostic tests in patients classified as
observation, suspect, and probable SARS cases
Project Description
Principal Investigators
Grants Awarded in 2003
Collaborator
Lymphoma cell interactions with endothelial adhesion molecules
under flow
Principal Investigator
Collaborator
: Dr Lim Yaw Chyn
: Assoc Prof Chong Siew Meng
Principal Investigator
Collaborator
Quantitative real-time polymerase chain reaction (Q-PCR):
molecular biology diagnostic technique applied to diagnosis,
prognostication and therapeutic management of infective posttransplantation complications and of haematological malignancies
Principal Investigator
Collaborators
Start-up grant funded by OLS - as above
: Dr Lim Yaw Chyn
: Assoc Prof Chong Siew Meng
Prospective and retrospective, high-throughput construction of
annotated frozen and paraffin tissue microarrays (TMA) linked
to assessment of histomorphology, immunophenotype and RNA
in-situ hybridization: Towards the establishment of molecular
information arrays
Principal Investigator
Collaborators
: Assoc Prof Evelyn S C Koay
: Dr Patrick H C Tan (SGH),
Dr P Kuperan (TTSH),
Dr Manuel Salto-Tellez,
Dr Liu Te Chih (NUH),
Assoc Prof Chong Siew Meng,
Assoc Prof S K Sethi,
Dr B H Tan (SGH),
Dr Gamini Kumarasinghe (NUH),
Dr Pary Sivaraman (NUH)
Ongoing Projects
: Dr Manuel Salto-Tellez
: Assoc Prof Evelyn S C Koay,
Dr Robert Hewitt,
Dr Thomas Putti,
Assoc Prof Chong Siew Meng,
Dr Richie Soong
Establishing the prevalence and prognostic significance of the
internal tandem duplication and the activating D835 point
mutations of the Flt3 gene in adult acute myeloid leukaemia
Preliminary studies to test the clinical relevance of the metastasissuppressing gene in the progression of colorectal and breast
cancer towards a metastatic phenotype
Principal Investigator
Collaborators
: Assoc Prof Evelyn S C Koay,
Dr Timothy Barkham (TTSH),
Dr Lee May Ann (DMERI)
: Dr Masasumi Inoue (IMCB)
: Dr Robert E Hewitt
: Dr Emma Shtivelman,
Prof Yoshiaki Ito,
Dr Kosei Ito
Principal Investigator
Collaborators
: Assoc Prof Evelyn S C Koay
: Ms Chang Ti Ling,
Dr Manuel Salto-Tellez,
Assoc Prof Kueh Yan Koon
Intrinsic variability in the detection of micrometastases in lymph
nodes for re-staging of colorectal cancer: effect of individual
markers and tissue samples
Principal Investigator
Collaborators
A representative case of cutaneous squamous cell carcinoma displaying positive
intranuclear staining for human telomerase reverse transcriptase activity (insitu hybridization technique)
84
: Dr Manuel Salto-Tellez
: Assoc Prof Evelyn S C Koay,
Ms Kong Say Li,
Assoc Prof Adrian Leong
Preparing digested peptides for mass spectrometric analysis in the search
for breast tumour biomarkers, a collaborative research study between the
Department of Pathology and the Molecular Diagnosis Centre at NUH, using
genomics, proteomics, immunohistochemical and cytogenetics techniques
Faculty of Medicine Research Report 2003
Physiopathological animal models of disease
Chang T L, M Salto-Tellez, T P Thamboo, Y S Lee and E S C Koay
Principal Investigator
Collaborator
T-cell receptor (TCR) gene rearrangements in cutaneous T-cell
lymphoproliferative disorders: validation and clinical application.
In Proceedings of the 15th Lorne Cancer Conference, pp. A1102.
Paper presented at 15th Lorne Cancer Conference, 13-16 February
2003, Erskine on the Beach, Lorne, Victoria, Australia).
: Dr Manuel Salto-Tellez
: Dr Lim Sai-Kiang
Detection of bone marrow-derived chimeric cells in the pancreas
of transplanted patients
Principal Investigator
Collaborator
: Dr Manuel Salto-Tellez
: Dr Bernat Soria
Microsatellite instability (MSI) and mismatch repair genes in
cases of hereditary nonpolyposis colorectal cancer syndrome
(HNPCC) and sporadic colorectal cancers: relation to prognosis
and methodology for screening of affected families
Principal Investigator
Collaborators
: Assoc Prof Evelyn S C Koay
: Dr Manuel Salto-Tellez,
Dr Lee Soo Chin (NUH),
Assoc Prof Adrian Leong
Detection of gene rearrangements involving the Alk-1 locus at
chromosome 2p23 using a fluorescence in-situ hybridization
probe on archival tissue: a study of 101 cases characterized by
histomorphology and immunohisto-chemistry
Principal Investigator
Co-Principal Investigators
Collaborator
: Dr Tan Hwan Cheong, Leonard
: Assoc Prof Evelyn S C Koay,
Assoc Prof Chong Siew Meng
: Dr Tan Soo Yong (TTSH)
HHV6 in transplant recipients
Principal Investigators
Collaborators
: Dr Tan Ban Hock (SGH),
Assoc Prof Evelyn S C Koay
: Dr H N Leong (SGH),
Dr L Y Hsu (SGH),
Dr A Kurup (SGH),
Dr P H C Tan (SGH),
Dr H C Toh (SGH),
Dr V Anantharaman (SGH)
Chiu L L, E S C Koay, N H Chan and M Salto-Tellez
Sequence confirmation of the EWS-WT1 fusion gene transcript
in the peritoneal effusion of a patient with desmoplastic small
round cell tumor. Diagnostic Cytopathology 29 (2003): 341-343.
Chiu L L, G H Leow, V T K Chow, P A Tambyah and E S C Koay
The use of an in-house RT-PCR assay for dengue virus detection
in the differential diagnosis for patients with possible SARS. Paper
presented at the 6th Asia Pacific Congress of Medical Virology,
7–10 December 2003, Kuala Lumpur, Malaysia.
Huan P T, L L Chiu, S Tow, M Salto-Tellez and E S C Koay
Detection of known and novel mutations in patients with suspected
Leber’s hereditary optic neuropathy in Singapore. Paper presented
at the XIX International Congress of Genetics 2003, 6–11July
2003, Melbourne, Australia.
Huang C H, I Kuo, H Xu, Y S Lee and K Y Chua
Mite allergen induces, allergic dermatitis with concomitant
neurogenic inflammation in mouse. Journal of Investigative
Dermatology, 121 (2003): 289-293.
Khoo M J, L L Chiu, K Razvi and E S C Koay
Validation of a DNA chip assay for identification and speciation
of human papillomavirus (HPV) in endocervical swabs. Journal
of Molecular Diagnostics, 5 (2003): 272. (Paper presented at the
Association for Molecular Pathology Annual Meeting 2003, 20–23
November 2003, Orlando, Florida, USA).
Koay E S C
International Publications
Chang T L, M Salto-Tellez, Y K Kueh and E S C Koay
Simplified capillary electrophoresis detection of the Flt-3 internal
tandem duplications and D835 point mutations in acute myeloid
leukaemia. Haematologica, 88 (2003): ELT04.
Chang T L, M Salto-Tellez, T P Thamboo, Y S Lee and E S C Koay
Diagnostic validation of a capillary electrophoresis analysis of
TCRg gene rearrangements: Prediction of malignant transformation
of cutaneous T-cell lymphoproliferative disorders. Clinical
Chemistry, 49 (2003): 513-515.
Faculty of Medicine Research Report 2003
Molecular aspects of laboratory diagnosis of cancer. Paper
presented at the Royal College of Pathologists of Australia and
Australasian Association of Clinical Biochemists Chemical
Pathology course, 10-14 February 2003, University of Tasmania,
Launceston, Tasmania, Australia.
Koay, E S C and W Y Chong
Molecular detection of aspergillus infection in human tissues by
real-time polymerase chain reaction. In Nucleic acid markers for
bacterial and viral infections in intensive care and
immunocompromised patients: Current status and future trends,
compiled by International Federation of Clinical Chemistry and
Laboratory Medicine and Roche Diagnostics GmbH, pp. 16. (Paper
presented at 9th Bergmeyer Conference Master Discussion on
Improving the Clinical Value of Laboratory Data, 24-26 March
2003, Eibsee Hotel, Grainau, Garmisch-Partenkriche, Germany).
85
Koay E S C, K Singh, L L Chiu, C K Chow and K Gamini
Singh K, L Ajit, L Chiu, C Chow, V Chow and E S C Koay
Laboratory diagnosis of dengue: Appropriate use of PCR (Abstract).
In Proceedings of the 19th Annual Clinical Virology Symposium,
compiled by University of South Florida College of Medicine, pp.
T52. (Paper presented at 19th Annual Clinical Virology Symposium
and Annual Meeting of the Pan American Society for Clinical
Virology, 27-30 April 2003, Hilton Clearwater Beach Resort,
Clearwater, Florida, United States).
Appropriate use of RT-PCR for the laboratory diagnosis of dengue
fever. Paper presented at the 6th Asia Pacific Congress of Medical
Virology, 7–10 December 2003, Kuala Lumpur, Malaysia.
Lau G, T P Thamboo and S H Lai
Tan K B, T P Thamboo and G C Raju
Fatal pulmonary thromboembolism in Singapore: Has anything
changed? Medicine Science and the Law, 43, 4 (2003): 307-314.
Xanthomatous Pseudotumour. An unusual post-chemotherapy
phenomenon in breast cancer. Archives of Pathology & Laboratory
Medicine, 127, 6 (2003): 739-741. (Case Report).
Mangold K A, R U Manson, R B Thomson Jr., E S C Koay, L A Peterson
and K L Kaul
Validation of real-time PCR and melt curve analysis for the
detection and speciation of Plasmodium (Abstract). Journal of
Molecular Diagnostics, 5, 4 (2003): 277. (Paper presented at the
Association for Molecular Pathology Annual Meeting 2003, 20–23
November 2003, Orlando, Florida, USA).
Tan K B, M K Premasiri and C P Thomas
Uterine malignant mixed mullerian tumour with pilomatrixomalike areas (Letter to editor). Pathology, 35, 6 (2003): 532-533.
Tan L H C and S M Chong
Grade II nodular sclerosing Hodgkin lymphoma commonly mimics
non-Hodgkin lymphomas with anaplastic morphology: a pathologic
review of 42 cases reclassified by current WHO criteria (Abstract).
Modern Pathology, 16, 1 (2003): 255A.
Tan L H C, Elaine Do, S M Chong and E S C Koay
Nealda Leila, M Y, A Wee, L Y Lim and E Khor
Flexible chitin films as potential wound dressing materials: wound
model studies. Journal of Biomedical Materials Research, 66A
(2003): 224-232.
Ng W L and E S C Koay
Human papillomavirus (HPV) genotyping by PCR-direct
sequencing approach. Paper presented at the 6th Asia Pacific
Congress of Medical Virology, 7th – 10th December 2003, Kuala
Lumpur, Malaysia.
Detection of ALK gene rearrangements in formalin-fixed, paraffinembedded tissue using a fluorescence in-situ hybridization (FISH)
probe: A search for optimum conditions of tissue archiving and
preparation for FISH (Editorial section). Molecular Diagnosis, 7,
1 (2003): 27-33.
Thamboo T P and Y S Lee
Pseudocystic leiomyoma of the ovary: A case report and literature
review. Pathology, 35, 6 (2003): 534-535.
Thamboo T P, L C H Liew and G C Raju
Söller R, E S C Koay, S Looareesuwan and F Zedler
Rapid and sensitive detection of malaria by real-time PCR
(Abstract). In Abstracts, Kongress fü Infektianskrankheitan und
Tropenmedize (International Congress for Tropical Medicine),
ABS-5911-00349. Berlin, February 2003. (Paper presented at
International Congress for Tropical Medicine, February 2003,
International Conference Centre, Berlin, Germany).
Salto-Tellez M, S L Kong, A P K Leong and E S C Koay
Intrinsic variability in the detection of micrometastases in lymph
nodes for re-staging of colorectal cancer: Effect of individual
markers and tissue sample. European Journal of Cancer, 39, 9
(2003): 1234-1241.
Salto-Tellez M, D H Zhang, L L Chiu, S C Wang, B Nilsson and E S C Koay
Immunocytochemistry versus molecular fingerprinting of
metastases. Cytopathology 14 (2003): 186-190.
Satkunanantham K, V Prem Kumar, S M Chong and A Thambyah
The Natural History of Spontaneous Osteonecrosis of the Medical
Tibial Plateau. Journal of Bone and Joint Surgery. British Volume,
7, B (2003): 983-988.
86
Adrenal leiomyosarcoma: A case report and literature review.
Pathology, 35, 1 (2003): 47-49.
Thamboo T P, K B Tan, S Wang and M Salto-Tellez
Extra-hepatic embolisation of Y-90 micropheres from Selective
Internal Radiation Therapy (SIRT) of the liver. (Letter to Editor).
Pathology, 35, 4 (2003): 351-353.
Tan J M M, E P C Tock and V T K Chow
The novel human MOST-1 (c8orf17) gene exhibits tissue
specific expression, maps to chromosome 8q24.2, and is
overexpressed/amplified in high grade cancers of the breast
and prostate. Molecular Pathology, 56, 2 (2003): 109-115.
Thomson R, M Lewandowski, K Mangold, K Kaul, E S C Koay and
K Singh
Rapid detection of Staphylococcus aureus (SA) and methicillinresistant SA (MRSA) directly from nasal surveillance swabs using
real-time PCR (R-PCR) (Abstract). In Proceedings of the 40th
Annual Meeting of the Infectious Diseases Society of American,
in Clinical Infectious Diseases (ISSN: 1058-4838). (Paper presented
at 4th Annual Meeting of the Infectious Diseases Society of
America, 24-27 October 2002, Chicago, Michigan, United States).
Faculty of Medicine Research Report 2003
Wee A and B S M Nilsson
Highly well differentiated hepatocellular carcinoma and benign
hepatocellular lesions: Can they be distinguished on fine needle
aspiration biopsy? Acta Cytologica, 47 (2003): 16-26.
Wee A, T P Thamboo and A Thomas
Not all alpha-fetoprotein-producing carcinomas in the liver are
of primary hepatic origin: A fine needle aspiration biopsy
experience. Acta Cytologica, 47 (2003): 799-808.
Zhang D-H, M Salto-Tellez, T C Putti, E Do and E S C Koay
Reliability of tissue microarrays in detecting protein expression
and gene amplification in breast cancer. Modern Pathology, 16,
(2003): 79-85.
Zhang D-H, M Salto-Tellez, E Do, T C Putti and E S C Koay
Evaluation of HER-2/neu oncogene status in breast tumors on
tissue microarrays. Human Pathology, 34 (2003): 362-368.
Contact Information
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Zhang D-H, M Salto-Tellez, L L Chiu, L Shen and E S C Koay
Tissue microarray study for classification of breast tumors. Life
Sciences, 73 (2003): 3189-3199.
Zhang D, M Salto-Tellez, L Shen and E S C Koay
A model of molecular classification of breast tumours based on
tissue microarrays: molecular profiling and monothetic cluster
analysis (Abstract). In Proceedings of the 15th Lorne Cancer
Conference. Australia, 1 February 2003. (Paper presented at 15th
Lorne Cancer Conference, Melbourne, Australia).
Staff Profile
Associate Professor and Head
Professors
:
:
Professorial Fellows
:
Associate Professors
:
Assistant Professors
:
Adjunct Assistant Professor
Senior Tutors
:
:
Research Fellow
:
Chong Siew Meng
Lee Yoke Sun
Aileen Wee
Aw Tar Choon
Alexander R Chang
K Shanmugaratnam
Edward Tock Peng Chong
G C Raju
Teh Ming
Evelyn S C Koay
Sunil K Sethi
Thomas C Putti
M Salto-Tellez
Tan Hwan Cheong, Leonard
Robert E Hewitt
Lim Yaw Chyn
Richie Soong
Tan Kong Bing
Thomas P Thamboo
Nga Min En
Zhang Daohai
Faculty of Medicine Research Report 2003
87
Assoc Prof Chong Siew Meng
Head of Department
6772-4300 / 6772-4313
pathead@nus.edu.sg
Assoc Prof Teh Ming
Department Research Director
6772-4306
pattehm@nus.edu.sg
Assoc Prof E S C Koay
Department Research Director
6772-4564
patkoaye@nus.edu.sg
6778-0671
Department of Pathology
National University of
Singapore
5 Lower Kent Ridge Road
Singapore 119074
http://www.med.nus.edu.sg
/path/pathwebF.htm
INTRODUCTION
The Department is involved in both basic and clinical pharmacology
research. The Department has organised its research efforts into four
main areas including Pharmacogenetics/Pharmacokinetics,
Neuropharmacology, Immunopharmacology, and Cardiovascular
Pharmacology. Members of the Department work together in these
general areas and collaborate with staff in other Departments and
elsewhere in Singapore. The longer term strategic aim is to increase the
quality of research output and maintain a successful research focus
which is competitive with other academic institutions worldwide.
Specific research topics of interest in the current year include,
relationship of genetics to variability in cardiovascular responses and
in susceptibility to disease,
optimization of anti-cancer (and other) drug therapy from a
pharmacokinetics perspective,
gene and protein expression and involvement of local hormones
and transmitters in animal models of inflammation (asthma,
pancreatitis, septic shock),
receptor gene expression and pharmacological modulation of
experimental models of stroke,
role of pharmacological mediators in anxiety/depression/fear and the
response to psychoactive drugs,
evaluation of novel derivatives of des-aspartate angiotensin I in
cardiovascular and other disease states and,
DEPARTMENT OF
Pharmacology
therapeutic uses of agents derived from natural products with particular
reference to potential anti-cancer agents and hypolipidaemics.
88
Faculty of Medicine Research Report 2003
Project Description
Pathogenesis of acute pancreatitis and associated lung injury:
The role of neurogenic inflammation
PrincipaI Investigator
Collaborators
Grants Awarded in 2003
Studies on three Chinese medicinal herbs for their effects on
appetite and immune parameters in normal doxorubicin-treated
P388 Tumour-bearing mice
Principal Investigator
: Assoc Prof Benny Tan
C-C Chemokines in Inflammation : Acute pancreatitis versus sepsis
Principal Investigator
: Dr Madhav Bhatia
Breakdown of Acetylcholine-induced potentiation of NMDA
Receptor Function As A Putative Mechanism of Glutamatergic
Hypofunction And Cognitive Decline
Principal Investigator
Collaborators
Drugs for “A Beautiful Mind” – A Start-Up Project On The
Neuropsychopharmacology of the amelioration of cognitive
dysfunction by atypical antipsychotics
Principal Investigator
Collaborators
: Assoc Prof Tan Chay Hoon
: Dr Gavin S. Dawe,
Assoc Prof Peter Wong,
Assoc Prof Ong Wei Yee,
Ms Psyche Lee (Biological Sciences)
Vascular pharmacology of a novel gasomediator, hydrogen
sulphide; Implications of a new treatment of septic shock/ multiple
organ dysfunction
Principal Investigator
Collaborators
: Prof Philip Moore
: Dr Madhav Bhatia,
Assoc Prof Shabbir Moocchala (DMERI)
Molecular Mechanisms of the CCK2 Receptor in the regulation
of fear and anxiety: Generation & Analysis of an inducible CCK
gene deletion in mouse
Principal Investigator
Co-Principal Investigator
: Dr Madhav Bhatia
: Prof A. Basbaum
(University of California),
Prof C. Pothoulakis
(Harvard Medical School),
Prof J. Neoptolemos
(University of Liverpool)
: Assoc Prof Peter Wong
: Dr MKP Lai (SGH),
Dr CBT Ang (NNI),
Dr CP Chen (SGH/NNI),
Dr Gavin S. Dawe,
Dr CM Low
Angiotensins And Cardiac Infarction
Principal Investigator
: Assoc Prof Sim Meng Kwoon
+
cAMP Regulation of Herg K Channel Expression and Function
Principal Investigator
: Dr Bian Jinsong
Cardioprotective effects of active ingredients isolated from Salviae
Miltiorrhizae after myocardial infarction
Principal Investigator
Collaborators
: Dr Zhu Yi Zhun
: Assoc Prof Benny Tan,
Dr Matt Whiteman
Evaluation of Angino (purified Salvia Miltiorrhizae) in hearts
Principal Investigator
: Dr Zhu Yi Zhun
: Assoc Prof Peter Wong
: Dr Zhu Yi Zhun
Preparation of tissue subcellular fractions for receptor binding studies
Faculty of Medicine Research Report 2003
89
Phenotyping of metabolising enzymes
Proteomics of Airway Inflammation: Identification of pathogenetic
molecules and therapeutic targets
Ongoing Projects
Pharmacokinetic Study of Thalidomide In Patients with unresectable
Hepatocellular Carcinoma
Principal Investigator
Collaborators
: Assoc Prof Lee How Sung
: Dr Goh Boon Cher (NUH),
Assoc Prof Kong Hwai Loong,
Leow Chon Ker,
Robert Lim (NUH)
Endothelin receptors expressed in neurons and microglia in the
acute phase of brain ischaemia
Principal Investigator
Collaborators
: Assoc Prof Peter Wong
: Dr Zhu Yi Zhun,
Dr YK Ng,
Assoc Prof Fred Wong
Development and Pharmacokinetics of topotecan antiresistance
stealth liposomes
Principal Investigator
Collaborators
Principal Investigator
Co-Principal Investigators
: Assoc Prof Lee How Sung
: Goh Boon Cher (NUH),
Lu Wan Liang (Peking University),
Alex Chang (JHS)
Neurogenic Inflammation in pancreatitis and associated lung
injury: novel possibilities for therapeutic interventions
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Assoc Prof Sim Meng Kwoon
Design, application and validation of a novel computational model
for population pharmacokinetic and pharmacodynamic modeling
Principal Investigator
Collaborators
: Dr Madhav Bhatia
: Prof Allan Basbaum
(University of California),
Prof John Neoptolemos
(University of Liverpool)
Stem Cell Transplants for adult brain repair: Do human umbilical
cord blood stem cells show functional transdifferentiation in
animal model of ischaemic stroke
Cardiovascular Actions of Angiotensin IV
Principal Investigator
: Assoc Prof Fred Wong
: Assoc Prof Chang Chan Fong,
Assoc Prof Tan Tin Wee,
Dr Cynthia Chee Bin Eng (TTSH),
Dr John A Abisheganaden (TTSH),
Dr Chng Hiok Hee (TTSH),
Dr Leong Khai Pang (TTSH)
: Dr Gavin S. Dawe
: Assoc Prof Wong Meng Cheong
(SGH),
Assoc Prof Shabbir Moocchala
(DMERI),
Dr Lu Jia (DMERI),
Dr Ang Beng Ti, Christopher (TTSH),
Assoc Prof Xiao Zhi-Cheng (SGH),
Assoc Prof Peter Wong
Investigating the neurotoxicity of cysteine in ischaemia using in
vivo animal models of stroke and in vitro primary cell cultures
: Prof Edmund Lee
: Dr Zeng Yingzhi (IHPC),
Dr Wu Ping (IHPC),
Assoc Prof Shabbir Moocchala
(DMERI),
Dr Balram Chowbay (NCC)
Principal Investigator
Collaborators
: Assoc Prof Peter Wong
: Dr CP Chen (SGH/NNI),
Prof B Halliwell
Pharmacogenetic characterization of drug response-population
genetic studies, identification & characterization of novel genetic
variants in drug transporter
Principal Investigator
Collaborators
: Prof Edmund Lee
: Dr Caroline Lee,
Dr Gavin S. Dawe
Do Noradrenergic mechanisms play a role in the cognitive effects
of atypical antipsychotics? - A neuropsychological and functional
magnetic resonance (FMRI) study
Principal Investigator
Collaborators
: Dr Gavin S. Dawe
: Assoc Prof Rathi Mahendran,
Dr Lyn Chua (IMH),
Dr Sitoh Yi Yian (TTSH),
Assoc Prof Tan Chay Hoon,
Dr Verma Swapna (IMH)
High performance liquid chromatography studies for monitoring
pharmacokinetic profile of novel drugs
90
Faculty of Medicine Research Report 2003
Chemokines as potential therapeutic targets for acute respiratory
distress syndrome
Principal Investigator
Collaborator
: Dr Madhav Bhatia
: Dr Lu Jia (DMERI)
Understanding regulation of fear in primates
Principal Investigator
Collaborator
: Dr Zhu Yi Zhun
: Assoc Prof Shabbir Moocchala (DMERI)
Effects of Urotensin-II on heart
Principal Investigator
: Dr Zhu Yi Zhun
Anti-anxiety effects of Salviae Miltiorrhizae in the treatment of
anxiety/fear
Principal Investigator
Collaborator
: Dr Zhu Yi Zhun
: Assoc Prof Benny Tan
Signal transduction antisense therapy for asthma in an animal
model
Principal Investigator
Collaborators
: Assoc Prof Fred Wong
: Assoc Prof Chang Chan Fong,
Prof Edmund Lee
Studies in animal models of Type II diabetes to derive bioactive
compounds from Morinda officinalis and Pereskia grandifolia
with effects on blood glucose, lipids and antioxidant levels
Principal Investigator
: Assoc Prof Benny Tan
International Publications
Moore P.K., Bhatia, M., Moochhala, S
Hydrogen sulphide: from the smell of the past to the gas of the
future. Trends in Pharmacological Sciences, 24, 609-611.
Bhatia M, Proudfoot AE, Wells TN, Christmas S, Neoptolemos JP,
Slavin J
Treatment with Met-RANTES reduces lung injury in caeruleininduced pancreatitis. Br J Surg., 90, 698-704.
Bhatia M, Slavin J, Cao Y, Basbaum AI, Neoptolemos JP
Preprotachykinin-A gene deletion protects mice against acute
pancreatitis and associated lung injury. Am J Physiol Gastrointest
Liver Physiol., 284, G836.
Bhatia M
Tachykinins as therapeutic targets in inflammation. Curr Med
Chem, Anti-Infl Anti-Allergy Drugs. 2: 19-27.
Tsang SW, Lai MK, Francis PT, Wong PT, Spence I, Esiri MM, Keene J,
Hope T, Chen CP
Serotonin transporters are preserved in the neocortex of anxious
Alzheimer's disease patients. Neuroreport, 14, 1300.
Wang H, Zhu YZ, Farook JM, Moochhala S, Teo AL, Lee LK, Wong PT
Understanding the regulation of genes involved in impulse control
and suicidal behaviour
Genetic variations in CCK2 receptor in PVG hooded and SpragueDawley rats and its mRNA expression on cat exposure. Behav
Neurosci., 117, 390.
Principal Investigator
Collaborators
Ang ET, Wong PT, Moochhala S, Ng YK
: Assoc Prof Tan Chay Hoon
: Dr Tan Ene Choo (DMRI-DSTA),
Dr Patrick Tan (NCC-DMRI)
Stem cells and the Neurobiology of Ageing: A New Frontier for
Molecular Pharmacology and Experimental Therapeutics in AntiAgeing Medicine.
Principal Investigator
Collaborators
: Dr Gavin S. Dawe
: Dr Sohail Ahmed (IMCB),
Dr Gerald Udolph (IMCB),
Assoc Prof Xiao Zhi-Cheng (SGH)
Neuroprotection associated with running: is it a result of increased
endogenous neurotrophic factors? Neuroscience, 118, 345.
Wang H, Zhu YZ, Wong PT, Farook JM, Teo AL, Lee LK, Moochhala S
cDNA microarray analysis of gene expression in anxious PVG and
SD rats after cat-freezing test. Exp Brain Res., 149, 421.
Zhu YC, Zhu YZ, Lu N, Wang MJ, Wang YX, Yao T
Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy
and cardiac remodelling. Clin Exp Pharmacol Physiol., 30, 918.
Ji X, Tan BK, Zhu YC, Linz W, Zhu YZ
Comparison of cardioprotective effects using ramipril and DanShen
for the treatment of acute myocardial infarction in rats. Life Sci.,
73, 1426.
Nirthanan S, Charpantier E, Gopalakrishnakone P, Gwee MC, Khoo HE,
Cheah LS, Kini RM, Bertrand D
Neuromuscular effects of candoxin, a novel toxin from the venom
of the Malayan krait (Bungarus candidus). Br J Pharmacol.,
139, 844.
Faculty of Medicine Research Report 2003
91
Nirthanan S, Gopalakrishnakone P, Gwee MC, Khoo HE, Kini RM
Tan EC, Chan AO, Tan CH, Mahendran R, Wang A, Chua HC
Non-conventional toxins from Elapid venoms. Toxicon., 41,
397-407.
Case-control and linkage disequilibrium studies of the tryptophan
hydroxylase gene polymorphisms and major depressive disorderPsychiatr Genet., 13, 154.
Sim MK, Qui XS
Angiotensins in plasma of hypertensive rats and human. Regul
Pept., 111, 182.
Tan EC, Tan CH, Karupathivan U, Yap EP
Mu opioid receptor gene polymorphisms and heroin dependence
in Asian populations. Neuroreport, 24, 572.
Duan W, Kuo IC, Selvarajan S, Chua KY, Bay BH, Wong WSF
Antiinflammatory effects of genistein, a tyrosine kinase inhibitor,
on a guinea pig model of asthma. Am J Respir Crit Care Med.,
167, 192.
Chong SA, Tan EC, Tan CH, Mythily, Chan YH
Polymorphisms of dopamine receptors and tardive dyskinesia
among Chinese patients with Schizophrenia - Am J Med Genet.,
116B, 54.
Liu QY, Tan BK
Relationship between anti-oxidant activities and doxorubicininduced lipid peroxidation in P388 tumour cells and heart and
liver in mice. Clin Exp Pharmacol Physiol., 30, 188.
Lee HS, Goh BC, Fan L, Khoo YM, Wang LZ, Lim R, Ong AB, Chua C
Raevskii VV, Dawe GS, Stevenson JD
Wang LZ, Goh BC, Grigg ME, Lee SC Khoo YM, Lee H
Endogenous dopamine modulates corticopallidal influences via
GABA. Neurosci Behav Physiol., 33, 844.
A rapid and sensitive liquid chromatography/tandem mass
spectrometry method for determination of docetaxel in human
plasma. Rapid Commun Mass Spectrom.17:1548-1552.
Phenotyping CYP3A using midazolam in cancer and non-cancer
Asian Patients. Br J Clin Pharmacol 55:270-277.
L. Lue, T. Yao, Y.Z. Zhu, G. Y. Huang, YX Cao, YC Zhu
Chronic all-trans retinoic acid treatment prevents medial thickening
of intramyocardial coronary arteries in spontaneously hypertensive
rats. Am J Physiology (Heart Circ Physiol.) 285, 1370-1377.
YC Zhu, YZ Zhu, T Yao
Angiotensin Receptors and Cardiac Remodeling. Clinical and
Experimental Pharmacology and Physiology, 30, 918.
Soo RA, Lim HL, Wang LZ, Lee HS, Millward MJ, Tok LT, Lee SC, Lehnert
M, Goh BC
Phase I trial of fixed dose-rate gemcitabine in combination with
carboplatin in chemonaive advanced non-small-cell lung cancer:
a Cancer Therapeutics Research Group study. Cancer Chemother
Pharmacol; 52:153-158.
Wang LZ, Goh BC, Lee HS, Noordhuis P, Peters GJ
IL-10 synergistically enhances GM-CSF-induced CCR1 expression
in myelomonocytic cells. Biochemical and Biophysical Research
Communications, 304, 417-424.
An expedient assay for determination of gemcitabine and its
metabolite in human plasma using isocratic ion-pair reversed
phase high performance liquid chromatography. Ther Drug Monit;
25: 552-557.
Ren M, F Watt, B K H Tan and B Halliwell
Balram C, Sharma A, Sivathasan C, Lee EJ
Correlation of iron and zinc levels with lesion depth in newly
formed atherosclerotic lesions. Free Radical Biology and Medicine,
34, 746-752.
Frequency of C3435T single nucleotide MDR1 genetic
polymorphism in an Asian population: phenotypic-genotypic
correlates. Br J Clin Pharmacol. 56, 78-83.
Swamy S M and B K H Tan
Balram C, Zhou Q, Cheung YB, Lee EJ
Intracellular glutathione depletion and reactive oxygen species
generation are important in alpha-hederin-induced apoptosis of
P388 cells. Molecular and Cellular Biochemistry, 245, 127-139.
CYP3A5*3 and *6 single nucleotide polymorphisms in three
distinct Asian populations. Eur J Clin Pharmacol., 59, 126.
Tan EC, Chong SA, Tan CH, Teo YY, Peng K, Mahendran R
Tumour necrosis factor-alpha gene promoter polymorphisms in
chronic schizophrenia - Biol Psychiatry 54,1211
The modulation of irinotecan-induced diarrhoea and
pharmacokinetics by three different classes of pharmacologic
agents. Oncol Rep. 10, 751.
Tan EC, Chong SA, Mahendran R, Tan CH, Teo YY
Gwee PC, Tang K, Chua JM, Lee EJ, Chong SS, Lee CG
Mu opioid receptor gene polymorphism and neuroleptic-induced
tardive dyskinesia in patients with schizophrenia - Schizophr
Research, 65:61-63.
Simultaneous genotyping of seven single-nucleotide
polymorphisms in the MDR1 gene by single-tube multiplex
minisequencing. Clin Chem., 49, 676.
Li H, Cheung W, Choo HH, Chan JHP, Lai PS and Wong WSF
92
Chowbay B, Sharma A, Zhou QY, Cheung YB, Lee EJ
Faculty of Medicine Research Report 2003
Chowbay B, Cumaraswamy S, Cheung YB, Zhou Q, Lee EJ
Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians
and the influence of MDR1 haplotypes on cyclosporin disposition
in heart transplant recipients. Pharmacogenetics, 13, 89-95.
Joseph JS, Thirumangalathu, S, Tsang, F, Wong, FSW, Kini, RM
Trocarin, a blood coagulation factor Xa homologue from
snake venom, causes inflammation and mitogenesis.
Toxicon,42,769-776.
Staff Profile
Professor & Head
Professors
:
:
Associate Professors
:
Assistant Professors
:
Senior Research Fellow
:
Moore, Philip Keith
Matthew Gwee Choon Eng
Edmund Lee Jon Deoon
Sim Meng Kwoon
Ti Teow Yee
Tan Chay Hoon
Tan Kwong Huat, Benny
Lee How Sung
Peter Tsun Hon Wong
Wong, Wai Shiu, Fred
Gavin Dawe
Madhav Bhatia
Bian Jinsong
Zhu Yi Zhun
Contact Information
Contact Person
:
Telephone
Facsimile
Email
Postal Address
:
:
:
:
Homepage
:
Prof Moore, Philip Keith
Head of Department
6874-3266
6873-7690
phcsec@nus.edu.sg
Department of Pharmacology
18 Medical Drive, Kent Ridge
Singapore 117597
http://www.med.nus.edu.eg/
phar/welcome.htm
Faculty of Medicine Research Report 2003
93
INTRODUCTION
The Department of Physiology has established and is seeking to build
on four major research areas as described below:
Neurobiology – research into cellular, system, and behavioral functions
of the central nervous system with emphasis on
the modulation of the pain experienced by the septo-hippocampal
region of the forebrain,
axonal guidance and neuronal plasticity in learning and memory, and
the role of voltage-gated calcium channels in neurotransmitter release,
muscle contraction, hormone secretion and gene expression.
Apoptosis and Cancer Biology – research into the cell’s growth
regulatory machinery, and the mechanism(s) involved in oncogenesis
and metastasis with emphasis on signal transduction, reactive oxygen
species, regulation of the death signal, cell cycle control, telomere biology,
gene regulation, oncogene and tumour suppressor action, drug resistance,
anti-tumour pharmacology.
Cell and Tissue Engineering – research into the structural and functional
relationships of cells and tissues that enable tissue repair and regeneration
with emphasis on
liver regeneration,
bioartificial livers, and
the role of extra-cellular matrices in the control of cell differentiation.
Immunology and Inflammation – research into the genetic controls and
mechanisms of immune function and development with emphasis on
T cell biology,
immune cell signaling,
immunogenetics, and
inflammation.
DEPARTMENT OF
Physiology
94
Faculty of Medicine Research Report 2003
Research programs were well supported by grants from the National
Medical Research Council, Biomedical Research Council and Academic
Research Fund (NUS). Twenty new grants were approved in 2003 totaling
close to $6 million.
Much of the research in our Department is done in conjunction with
collaborators at both national and international institutions including:
DMRI, Singapore; IMCB, Singapore; Johns Hopkins Singapore Pte Ltd,
Singapore; SGH, Singapore; TTSH, Singapore; Amgen Research Institute,
Toronto, Canada; Dept of Biomedical Engineering, Johns Hopkins School
of Medicine, USA; Dept of Molecular and Experimental Medicine, Scripps
Research Institute, USA; Dept of Pharmacology, Yale University School
of Medicine, USA; Dept of Physiology, Free University of Brussels, Belgium;
Dept of Toxicology, Karolinska Institute, Stockholm, Sweden; Dept of
Surgery, Prince of Wales University, Hong Kong; Institute of Bioengineering
and Bioscience, Georgia Institute of Technology, USA; Technical University,
Munich, Germany; Dept of Immunology, University of Glasgow, UK; Dept
of Immunology, University of Strathclyde, UK.
The Department published a total of 19 international papers, many in
highly ranked international journals. These include the EMBO Journal,
American Journal of Human Genetics, Cancer Research, FASEB Journal,
Journal of Biological Chemistry, American Journal of Respiratory and
Critical Care Medicine, Journal of Neuroscience, Cell Death and
Differentiation, Journal of Hepatology, Tissue Engineering, and Biomaterials.
Furthermore our department members were co-inventors in 2 patents
filed in 2003, one filed in the USA and another filed in the UK.
DEPARTMENT OF
Physiology
Faculty of Medicine Research Report 2003
95
Molecular mechanisms of the radio-resistance of human brain
tumours (International Union Against Cancer)
Project Description
Principal Investigator
Collaborators
Grants Awarded in 2003
Biochemical characterization of cubic membrane transition in
amoeba Chaos and alternative model systems
Principal Investigator
Collaborators
: Dr Deng Yuru
: Prof Sepp Kohlwein
(University of Graz, Austria),
Prof Carmen Mannella (USA),
Prof Francis Sluse
(University of Liege, Belgium)
Humoral immune responses against human coronavirus
SARS antigen and development of potential vaccines
and therapeutic antibodies
Principal Investigator
Collaborators
Cubic membranes: cellular adaptation and protection against
oxidative stress?
Principal Investigator
Collaborator
: Dr Deng Yuru
: Prof Sepp Kohlwein
(University of Graz, Austria)
Principal Investigator
Collaborators
: Dr Deng Yuru
: Prof Sepp Kohlwein
(University of Graz, Austria),
Prof Carmen Mannella (USA),
Prof Francis Sluse
(University of Liege, Belgium)
Principal Investigator
: Dr M Prakash Hande
:
: Dr Alan Lee
The implication of Plexin-B3/RhoGTPases interaction in
axon guidance
Principal Investigator
: Dr Alan Lee
Functional characterization of a novel axon guidance molecule
plexin-B3
Principal Investigator
Collaborators
BRCA1 and BRCA2 genes in telomere-chromosomal integrity
Principal Investigator
: Assoc Prof Koh Dow Rhoon
: Assoc Prof Eric Yap (DMRI),
Dr Howe Hwee Siew (TTSH),
Dr Chng Hiok Hee (TTSH)
Immunohistochemical localization of mouse Plexin-B3 expression
Molecular cytogenetics of human tumours: mFISH approach
and Molecular Cytogenetics Core Facility at the Oncology
Research Institute
Principal Investigator
: Assoc Prof Koh Dow Rhoon
: Assoc Prof Vincent Chow,
Dr Jaap Goudsmit (Crucell Holland B.V.),
Dr Jan H ter Meulen
(Crucell Holland B.V.),
Dr Menzo J.E. Havenga
(Crucell Holland B.V.)
Immunogenetics of systemic lupus erythematosus
Cubic membranes: a novel 3D nano-periodic biological structureimplications for cellular response to starvation and ischemia
Principal Investigator
Collaborators
: Dr M Prakash Hande
: Dr Razq Hakem (University of Toronto),
Dr Fabrizio d’Adda di Fagagna
(Milan, Italy),
Dr A. S. Balajee (Columbia University)
: Dr Alan Lee
: Dr Steve Cheung,
Dr Qi Zhong (IMCB)
Dr M Prakash Hande
Microinjection of mouse embryos
Slide preparation for immunostaining
96
Faculty of Medicine Research Report 2003
Mechanisms of drug-induced inhibition of inflammation and
leukocyte recruitment
Principal Investigator
: Dr Lina Lim
Characterization of basophil rolling and adhesion under
physiological flow conditions in vitro
Principal Investigator
Use of fluorescence in situ hybridisation techniques to study
the telomere-chromosome integrity in DNA repair deficient
mammalian cells
Principal Investigator
Collaborators
: Dr Lina Lim
Interplay between intracellular redox status and pro-apoptotic
protein Bax during drug-induced tumor cell death: potential
implications for cancer chemotherapy
Principal Investigator
Collaborator
: Assoc Prof Shazib Pervaiz
: Dr Marie-Veronique Clement
Study to assess the role of cellular redox status on intracellular
pH regulation and its effect on drug-induced apoptosis in tumor
cells and to develop novel molecules that sensitize tumor cells
to death stimuli by altering the redox status
Principal Investigator
Collaborator
: Assoc Prof Shazib Pervaiz
: Dr Marie-Veronique Clement
Evaluation of altered gene expression and resistance to
development of hepatocellular carcinoma in the liver of the
C/EBP gene knock-in mouse
Principal Investigator
Principal Investigator
Evaluation of foetal electrocardiography and foetal heart
rate variability
Principal Investigator
Collaborator
: Dr Wang Nai-dy
: Assoc Prof Ho Ting Fei
: Adj Assoc Prof Yip Chin Ling, William
Assessment of lung volumes and mechanics in infants and young
children with congenital heart disease
Principal Investigator
Collaborator
: Assoc Prof Ho Ting Fei
: Adj Assoc Prof Yip Chin Ling, William
Prevalence and clinical study of eating disorders in young females
Principal Investigator
Collaborators
: Dr Wang Nai-dy
Assessment of C/EBP
gene knock-in mouse embryonic stem
cells for the ability to differentiate into hepatocytes in vivo and
assessment of these stem cell-derived hepatocytes for resistance
to tumourgenesis
: Dr Manoor Prakash Hande
: Dr Razq Hakem (University of Toronto),
Dr Zhao-Qi Wang
(IARC (WHO), Lyon, France),
Dr David Chen (Lawrence Berkeley
Laboratory, Berkeley, CA, USA),
Dr Robert Weiss
(Cornell University, USA)
: Assoc Prof Ho Ting Fei
: Dr Lee Ee Lian (IMH),
Dr Liow Pei Hsiang (IMH),
Dr Samuel Cheng (IMH),
Dr Mollie Seow (MOH)
Role of heparin / heparan sulfate interacting protein (HIP) in
colon cancer cell proliferation and differentiation
Principal Investigator
Collaborators
Ongoing Projects
: Assoc Prof Hooi Shing Chuan
: Assoc Prof Adrian Leong,
Dr Manuel Salto-Tellez
Anti-bacterial activity of recombinant PRAP
Cubic membranes: a cellular response to oxidative stress?
Starvation vs. ischemia
Principal Investigator
:
Dr Deng Yuru
Principal Investigator
Collaborator
: Assoc Prof Hooi Shing Chuan
: Assoc Prof Eric Yap Peng Huat (DMRI)
Anti-bacterial activity of PRAP fragments and PRAP secreted
in tissue culture supernatants
PrincipaI Investigator
Collaborator
: Assoc Prof Hooi Shing Chuan
: Assoc Prof Eric Yap Peng Huat (DMRI)
Role of histone deacetylases in colorectal carcinogenesis
& metastasis
Principal Investigator
: Assoc Prof Hooi Shing Chuan
Histone deacetylase inhibitors- screening & mechanism of action
Principal Investigator
Collaborators
Study of chromosome translocations
Faculty of Medicine Research Report 2003
97
: Assoc Prof Hooi Shing Chuan
: Assoc Prof Lee Chee Wee,
Assoc Prof Maxey Chung
Differential gene expression in EL4 lymphoma cells and altered
susceptibility to oxysterol-induced cell death: A pilot study to
demonstrate a causal relationship
Differential gene expression profiling of human mast cells following
IgE/Antigen stimulation: Functional genomics analysis of selected
novel genes
Principal Investigator
Principal Investigator
: Prof Hwang Lam Hum, Peter
: Dr Alirio J. Melendez
Pain: state dependent changes and modulation by
hippocampal formation
Studies on the anaphylatoxin activation of neutrophils and
macrophages through their C5a receptor
Principal Investigator
Collaborator
Principal Investigator
: Assoc Prof Sanjay Khanna
: Dr Shabbir Moochhala (DMRI)
Investigations into the neural circuitry underlying hippocampal
nociceptive responses and its influence on formalin nociception,
an animal model of persistent pain
Principal Investigator
: Assoc Prof Sanjay Khanna
: Assoc Prof Koh Dow Rhoon
: Assoc Prof Chong Siew Meng
: Assoc Prof Koh Dow Rhoon
: Assoc Prof Fong Kok Yong,
Dr Yoon Kam Hon,
Dr Ng Swee Cheng
: Assoc Prof Lee Chee Wee
: Prof Giuseppe Pizzorno (Yale University
School of Medicine)
Characterization of mouse plexin-B3 structural gene and
construction of gene knockout vector
Principal Investigator
: Dr Alan Lee
Principal Investigator
Collaborator
Principal Investigator
Collaborator
: Dr Marie-Veronique Clement
: Assoc Prof Shazib Pervaiz
: Assoc Prof Shazib Pervaiz
: Dr Marie-Veronique Clement
: Dr Alirio J. Melendez
: Assoc Prof Hanry Yu
: Dr Gareth Griffiths (EMBL)
Influence of extra-cellular microenvironment on cellular dynamics
for tissue engineering
Principal Investigator
Collaborator
: Assoc Prof Hanry Yu
: Dr Gang Bao (Georgia Institute of
Technology, USA)
Cellular dynamics in engineered extra-cellular microenvironment
: Dr Alan Lee
Investigation of the intracellular signalling pathways initiated by
the anaphylatoxin C5a in monocytes and macrophages
Principal Investigator
Principal Investigator
Collaborator
Principal Investigator
Collaborators
Characterization of mouse plexin-B3 signaling cascades
Principal Investigator
: Assoc Prof Shazib Pervaiz
Organelle-specificity of the microtubule-based transport machinery
on phagosome and other intracellular organelles
Physiological function of nucleoside transporter proteins and
uridine phosphorylase in uridine homeostasis and 5-fluorouracil
based antitumour therapy
Principal Investigator
Collaborator
Principal Investigator
Intracellular acidification and decrease in superoxide anion: Novel
mechanism for bypassing Bcl-2 protection in tumor cells
T cell response to nucleosomes in lups patients with nephritis
Principal Investigator
Collaborators
Effector mechanisms that enhance sensitivity of tumor cells to
drug-induced apoptosis
Regulation of tumor cells response to apoptosis by reactive
oxygen intermediates
Immunoregulatory functions of CD30 in oral tolerance
and autoimmune states
Principal Investigator
Collaborator
: Dr Alirio J. Melendez
: Assoc Prof Hanry Yu
: Assoc Prof Hooi Shing Chuan,
Dr Chen Jia Ping, Paul
(Chemical & Environmental Engineering)
Vitrification of hepatocyte spheroids and encapsulated hepatocytes
Principal Investigator
Collaborator
: Assoc Prof Hanry Yu
: Dr Lilia Kuleshova
(Otani Women’s Clinic, Japan)
Identification of the phospholipid signalling pathways triggered
by FceRI in human mast cells: An antisense approach for the
identification of potential new targets for therapeutic intervention
Principal Investigator
: Dr Alirio J. Melendez
98
Faculty of Medicine Research Report 2003
Clement MV, JL Hirpara and S Pervaiz
International Publications
Shi DY, Deng Y, Liu SL, Zhang YD and Wei L
Redox stress regulates cell proliferation and apoptosis of human
hepatoma through Akt protein phosphorylation. FEBS Letters,
542(1-3): 60-64.
Hande MP, TV Azizova, CR Geard, LE Burak, CR Mitchell, VF Khokhryakov,
FK Vasilenko and DJ Brenner
Decrease in intracellular superoxide sensitizes Bcl-2-overexpressing
tumor cells to receptor and drug-induced apoptosis independent
of the mitochondria. Cell Death and Differentiation, 10(11):
1273-1286.
Pervaiz S
Resveratrol: From grapevines to mammalian biology. FASEB
Journal, 17(14): 1975-1985.
Ahmad KA, M-V Clement and S Pervaiz
Past exposure to densely ionizing radiation leaves a unique
permanent signature in the genome. American Journal of Human
Genetics, 72(5): 1162-1170.
Resveratrol inhibits hydrogen peroxide induced apoptosis by
creating an intracellular milieu non-permissive for death execution.
Annals New York Acad Sci. (In press)
Abraham J, B Lemmers, MP Hande, ME Moynahan, C Chahwan, A Ciccia,
J Essers, K Hanada, R Chahwan, AK Khaw, P McPherson, A Shehabeldin,
R Laister, C Arrowsmith, R Kanaar, SC West, M Jasin and R Hakem
Moh MC, LH Lee, X Yang and S Shen
Eme1 is involved in DNA damage processing and maintenance
of genomic stability in mammalian cells. EMBO Journal, 22(22):
6137-6147.
Wang Y, S Tan and SC Hooi
The HIP gene encoding a heparin/heparan sulfate interacting
protein is mutated in metastatic human colorectal cancer.
International Journal of Molecular Medicine, 11(4): 473-477.
Zhang J, H Wong, S Ramanan, D Cheong, A Leong and SC Hooi
The proline-rich acidic protein is epigenetically regulated and
inhibits growth of cancer cell lines. Cancer Research, 63(20):
6658-6665.
Luo N, LH Chew, KY Fong, DR Koh, SC Ng, KH Yoon, S Vasoo, SC Li and
J Thumboo
Do English and Chinese EQ-5D versions demonstrate measurement
equivalence? An exploratory study. Health and Quality of Life
Outcomes, 1(1): 7.
Luo N, LH Chew, KY Fong, DR Koh, SC Ng, KH Yoon, S Vasoo, SC Li and
J Thumboo
Validity and reliability of the EQ-5D self-report questionnaire in
English-speaking Asian patients with rheumatic diseases in
Singapore. Quality of Life Research, 12(1): 87-92.
Law JWS, AYW Lee, M Sun, AG Nikonenko, SK Chung, A Dityatev, M
Schachner and F Morellini
Decreased anxiety, altered place learning, and increased CA1
basal excitatory synaptic transmission in mice with conditional
ablation of the neural cell adhesion molecule L1. Journal of
Neuroscience, 23(32): 10419-10432.
Lim LHK and EM Wagner
Airway distension promotes leukocyte recruitment in rat tracheal
circulation. American Journal of Respiratory & Critical Care
Medicine, 168(9): 1068-1074.
Faculty of Medicine Research Report 2003
HEPN1, a novel gene that is frequently down regulated in
hepatocellular carcinoma, suppresses cell growth and induces
apoptosis in HepG2 cells. Journal of Hepatology, 39(4): 580-586.
Ong LL, CPN Er, A Ho, MT Aung and H Yu
Kinectin anchors the translation elongation factor-1d to
endoplasmic reticulum. Journal of Biological Chemistry, 278(34):
32115-32123.
Lu HF, WS Lim, J Wang, ZQ Tang, PC Zhang, KW Leong, SM Chia, H Yu
and HQ Mao
Galactosylated PVDF membrane promotes hepatocyte attachment
and functional maintenance. Biomaterials, 24(27): 4893-4903.
Wong SC, H Yu, SM Moochhala and JB So
Antisense telomerase induced cell growth inhibition, cell cycle
arrest and telomerase activity down-regulation in gastric and
colon cancer cells. Anticancer Research, 23(1A): 465-469.
Xu X, WC Yee, PYK Hwang, H Yu, CAA Wan, SJ Gao, KL Boon, HQ Mao,
KW Leong and S Wang
Peripheral nerve regeneration with sustained release of
poly(phosphoester) microencapsulated nerve growth factor within
nerve guide conduits. Biomaterials, 24(13): 2405-2412.
Yin C, SM Chia, CH Quek, H Yu, RX Zhuo, KW Leong and HQ Mao
Microcapsules with improved mechanical stability for hepatocyte
culture. Biomaterials, 24(10): 1771-1780.
Wong SCH, LL Ong, CPN Er, SJ Gao, H Yu and JBY So
Cloning of rat telomerase catalytic subunit functional domains,
reconstitution of telomerase activity and enzymatic profile of pig
and chicken tissues. Life Sciences, 73(21): 2749-2760.
Sun T, MLH Chan, Y Zhou, X Xu, J Zhang, XJ Lao, XW Wang, CH Quek, JP
Chen, KW Leong and H Yu
Use of ultrathin shell microcapsules of hepatocytes in bioartificial
liver-assist device. Tissue Engineering, 9(1): 65-75.
99
Staff Profile
Associate Professor and Head
Professor
Associate Professors
Adjunct Associate Professors
Associate Professorial Fellow
Assistant Professors
:
:
:
:
:
:
Visiting Fellow
Adjunct Senior Fellows
:
:
Senior Research Fellow
Research Fellows
:
:
Contact Information
Hooi Shing Chuan
Peter Hwang Lam Hum
Ho Ting Fei
Sanjay Khanna
Koh Dow Rhoon
Lee Chee Wee
Shazib Pervaiz
Hanry Yu
Graeme Guy
Walter Hunziker
Lee Kim Hock, Lionel
Li Fuk Loi, Benjamin
Soong Tuck Wah
Wong Chong Thim
Deng Yuru
Manoor Prakash Hande
Lee Beng Huat, Martin
Lee Yiu Wah, Alan
Lim Hsiu Kim, Lina
Lim Yaw Chyn
Alirio J. Melendez
Shen Shali
Wang Nai-dy
Yap Suen Mei, Celestial Therese
Sohail Ahmed
Lam Yeng Po, Paula
Li Peng
Ng Chun Yeen, Aylwin
Tan Boon Ooi, Patrick
Lilia Kuleshova
Zakaria Ali Moh. Almsherqi
Jayapal Manikandan
Dr Liu Jian-Jun
Ma Fengjuan
Pook Sim Hwee
Renji Reghunathan
Zhi Liang
Dr Zhu Jian Hang
100
Research Enquiries
Contact Person
Telephone
Email
:
:
:
Dr Alirio J. Melendez
6874-1697
phsmraj@nus.edu.sg
Postgraduate Enquiries
Contact Person
Telephone
Email
:
:
:
Dr Wang Nai-dy
6874-3663
phswnd@nus.edu.sg
General Enquiries
Contact Person
Telephone
Email
:
:
:
Asha Reka Das
6874-3223
phssec@nus.edu.sg
Postal Address
:
Fascimile
Homepage
:
:
Department of Physiology
Faculty of Medicine
National University of
Singapore
Blk MD9, 2 Medical Drive
Singapore 117597
6778-8161
http://www.med.nus.edu.sg
/phys/
Faculty of Medicine Research Report 2003
INTRODUCTION
The Strategic Research Initiatives of the Department include research on:
Psychiatric Epidemiology and Gerontological Research,
Early identification and treatment of psychiatric disorders, particularly
schizophrenia and related psychoses,
Psychological aspects of general medical and surgical conditions.
Our aim is to engage in collaborative research with local and overseas
partners in both clinical and basic sciences, leveraging on platform
technologies like functional neuro-imaging and molecular/genetic research.
RESEARCH
Research in psychosis by the First Episode Schizophrenia (FES) Study
Group has focused on the neuro-cognitive aspects of early psychosis. The
Gerontology Research Programme (GRP) is a flagship research initiative
of the Department and provides a systematic, coordinated programme of
research activities on the health of the elderly population in Singapore
that will help understanding the population aging transition and provide
the scientific information needed for formulating strategies of disease
prevention and health promotion. The SARS outbreak in 2003 prompted
research into the psychological reactions of healthcare workers in Singapore
and other SARS-affected countries.
DEPARTMENT OF
Psychological Medicine
Faculty of Medicine Research Report 2003
101
Postnatal Depression in Singaporean Women and their partners
Project Description
Principal Investigator
Collaborators
Grants Awarded in 2003
: Dr Cornelia Chee
: Dr Chong Yap Seng,
Assoc Prof Calvin Fones,
Ms Jasmine Tan Liam Kiau
Anger, social support and cardiovascular responses
Psychological and Behavioural Responses of Healthcare Workers
to the SARS Outbreak
Principal Investigators
Collaborators
: Assoc Prof Calvin Fones,
Prof David Koh
: Assoc Prof Lim MK,
Assoc Prof Chia SE
Collaborators
Cognitive Behaviour Therapy of Depressed Post-Myocardial
I n f a r c t i o n Pa t i e n t s : E f f e c t s o n C a r d i o va s c u l a r a n d
Haematological Measurements
Principal Investigator
Principal Investigator
Co-Principal Investigators
: Assoc Prof George D Bishop
: Dr Vicky Tan,
Dr Jeannette Jen-Mai Lee
: Dr Zhang Jin Ting,
Assoc Prof Calvin Fones,
Assoc Prof Ko Soo Meng
An epidemiological Study of Depression in Singapore
Principal Investigator
Co-Principal Investigators
: Adj Assoc Prof Leslie Lim
: Dr Chua Hong Choon (WH/IMH)
: Assoc Prof Ng Tze Pin,
Assoc Prof Calvin Fones
Biological markers of alcoholism: a comparative study of the
alcohol dehydrogenase and aldehyde dehydrogenase systems in
Indian and Chinese alcohol dependent patients
Ongoing Projects
Singapore Longitudinal Ageing Study (SLAS) is the principal
population-based longitudinal cohort study in the GRP
Principal Investigator
Collaborator
Principal Investigator
Collaborators
Anxiety Disorders in Singapore: a community survey
: Assoc Prof Ng Tze Pin
: Prof Kua Ee Heok,
Assoc Prof Calvin Fones,
Assoc Prof Ko Soo Meng
Principal Investigator
Collaborators
A preliminary neurocognitive study of "high functioning” nonschizophrenic relatives of schizophrenia patients
Principal Investigator
Collaborators
: Dr Tan Hao Yang
: Assoc Prof Calvin Fones,
Assoc Prof Ko Soo Meng
: Adj Assoc Prof Leslie Lim
: Assoc Prof Ng Tze Pin,
Assoc Prof Calvin Fones,
Prof Kua Ee Heok
International Publications
Differentiation of Mild Cognitive Impairment from Normal
Ageing and Alzheimer’s Disease in Older Adults in Singapore: A
Pilot Study
Principal Investigator
Collaborators
: Adj Assoc Prof Leslie Lim
: Assoc Prof Tan Chay Hoon
: Dr Martha Chiu
: Prof Kua Ee Heok,
Assoc Prof Ko Soo Meng,
Assoc Prof Wang Shih-chang,
Assoc Prof Tan Chay Hoon
Imaging the human mind
Ng TP, Fones CS, Kua EH
Preference, need and utilization of mental health services,
Singapore National Mental Health Survey. Aust N Z J Psychiatry.
2003;37(5):613-9.
Memory assessment
102
Faculty of Medicine Research Report 2003
Kua EH, Ko SM, Ng TP
Recent trends in elderly suicide rates in a multi-ethnic Asian city.
Int J Geriatr Psychiatry. 2003;18(6):533-6.
Verma SK, M Subramaniam, Chong SA, Kua EH
Substance Abuse in Schizophrenia. Social Psychiatry and Psychiatric
Epidemiology, 37: 326-328, 2003
Kua J, Kua EH and Tsoi W
A 20-year follow-up study of schizophrenia in Singapore. Acta
Psychiatrica Scandinavica, 108 (2003): 118-125
Foster PJ, Machin D, Wong TY, Ng TP, Kirwan JF, Johnson GJ, Khaw PT,
Seah SK
Determinants of intraocular pressure and its association with
glaucomatous optic neuropathy in Chinese Singaporeans: the
Tanjong Pagar Study. Invest Ophthalmol Vis Sci. 2003;44 (9):
3885-91.
Niti M, Ng TP
Avoidable hospitalisation rates in Singapore, 1991-1998: assessing
trends and inequities of quality in primary care. J Epidemiol
Community Health. 2003;57(1):17-22.
Kua EH
Staff Profile
Mental Health and family care of the elderly in Asia. International
Psychogeriatrics, 15, 7 (2003)
Kua EH, Clarice Hong
Attempted suicide by elderly Chinese in Singapore International
Psychogeriatrics, 3 (2003): 78-81
Ng TP, Wong ML, Hong CY, Koh KT, Goh LG
The use of complementary and alternative medicine by asthma
patients. QJM. 2003; 96 (10):747-54.
Associate Professor & Head
Professor
Associate Professors
:
:
:
Assistant Professor
Adjunct Associate Professor
Research Fellow
:
:
:
Contact Information
Ng TP, Niti M
Trends and ethnic differences in hospital admissions and mortality
for congestive heart failure in the elderly in Singapore, 1991 to
1998. Heart. 2003;89(8):865-70.
Ng TP, Niti M, Tan WC
Trends and ethnic differences in asthma hospitalization rates in
Singapore, 1991 to 1998. Ann Allergy Asthma Immunol.
2003; 90 (1):51-5.
Contact Person
Telephone
Facsimile
Email
Postal Address
:
:
:
:
:
Homepage
:
Tan WC, Xiang X, Qiu D, Ng TP, Lam SF, Hegele RG
Epidemiology of respiratory viruses in patients hospitalized with
near-fatal asthma, acute exacerbations of asthma, or chronic
obstructive pulmonary disease. Am J Med. 2003;115 (4):
272-7.
Exploring the mind in old age
Faculty of Medicine Research Report 2003
Calvin Fones Soon Leng
Kua Ee Heok
Ko Soo Meng
Ng Tze Pin
Tan Hao Yang
Leslie Lim
Lisa Chuah
103
Assoc Prof Ng Tze Pin
6772-4511
6777-2191
pcmngtp@nus.edu.sg
Department of Psychological
Medicine
National University of
Singapore
5 Lower Kent Ridge Road
Singapore 119074
http://www.med.nus.edu.sg/
pcm/
INTRODUCTION
The Department of Surgery comprises academic staff from the National
University of Singapore and clinical staff of the National University
Hospital. There are eight clinical divisions within the department namely
General Surgery, Urology, Plastic and Reconstructive Surgery, Cardiothoracic
Surgery, Neurosurgery, Paediatric Surgery, Colorectal Surgery and
Hepatobiliary and Pancreatic Surgery. In addition the Department also
co-ordinates the interdepartmental and multidisciplinary clinical services
associated with minimally invasive and transplantation surgery. The
Department carries out clinical, as well as undergraduate and postgraduate
teaching activities and both clinical and basic research.
The research carried out in the Department includes the areas of cancer
biology, wound healing, bone regeneration/grafting, liver transplantation,
cardiology, stem cells and islet cell transplantation. Funding for these
projects comes from the Biomedical Research Council, National Medical
Research Centre, The Academic Research Fund, The National Health Group
and The Singapore Cancer Society. Collaborations exist with other
departments in the Faculties of Medicine, Science and Engineering in
NUS and with the Institute of Molecular and Cell Biology, National
University Medical Institutes, Genome Institute of Singapore, the Defence
Military Research Institute as well as local Hospitals. International
collaborations with Research Institutes, Universities and companies
abroad have increased over the years.
The research highlights for this year include: the development of a new
stem cell differentiation initiative under the direction of Prof. Bernat
Soria; an initiative to study the use of adipose derived mesenchymal cells
for bone reconstruction; optimisation of the use of skeletal mycoblasts
in cardiac repair; chiemric pancreas formation; and the analysis of BRCA1
mutations in medullary cancers.
DEPARTMENT OF
Surgery
104
Faculty of Medicine Research Report 2003
Ongoing Projects
Project Description
Transplantation for type I Diabetes using the Edmonton protocol
Grants Awarded in 2003
Adipose-derived mesenchymal cells for bone reconstruction:
A preliminary study in a mouse model
Principal Investigator
Collaborators
: Assoc Prof Lim Thiam Chye
: Dr S Moochhala (DMRI),
Dr Thorsten Schantz
(Laboratory for BioMedical Engineering)
Intramyocardial engraftment of skeletal myoblast for cardiac
repair: optimization of transplantation conditions
Principal Investigator
Collaborators
: Assoc Prof Eugene Sim
: Dr H K Haider (NUMI),
Ms Jiang Shujia (NHC),
Assoc Prof Teh Ming
Principal Investigator
Co-Principal Investigators
Collaborators
Continuing Investigations into the Role of Epidermal Mesenchymal
Interactions in Keloid pathogenesis and Aberrant Skin
Fibroproliferation
Principal Investigators
Collaborators
Induction of chimeric pancreas formation by transplanting
mouse/rat embryonic organ rudiments
Principal Investigators
: Dr Dennis Wang,
Assoc Prof John Isaac
Are medullary breast cancers an indication for BRCA1 mutation
screening? A mutation analysis of 42 cases of medullary
breast cancer
Principal Investigator
Co-Principal Investigator
: Dr Sng Jen-Hwei
: Dr Philip Iau Tsau Choong
: Sir Roy Calne
: Assoc Prof John Isaac,
Dr Dennis Wang,
Assoc Prof Lee Kok Onn,
Assoc Prof Thai Ah Chuan
: Sum Chee Fang (AH),
Lim Su Chi (AH),
Dr Cheah Wei Keat,
Dr Pary Sivaraman,
Assoc Prof Wang Shih Chang
: Dr Ivor Lim,
Dr Phan Toan Thang
: Robert Qi (HKUST, SAR,
China formerly IMCB),
Assoc Prof Boon Huat Bay,
Sabine Werner
(ETH, Zurich, Switzerland),
Michael T Longaker (Stanford, USA)
Assessment of Myocardial Injury and C-Reactive Protein After
Coronary Artery Surgery: Effects of a Selective COX II Inhibitor
Principal Investigator
: Assoc Prof Wong Poo Sing
The prevalence of large exon rearrangements in the BRCA1 gene
in Asian early onset and familial breast cancer patients
Principal Investigator
Co-Principal Investigator
Collaborators
: Dr Sng Jen Wei
: Dr Philip Iau Tsau Choong
: Dr Lee Soo Chin (Oncology, NUS),
Prof John Wong
(Division of Haematology/
Oncology, NUS)
Engineered Bone Graft in the Reconstruction of the
Craniofacial Skeleton
Principal Investigator
Collaborators
: Assoc Prof Lim Thiam Chye
: Dr Chou Ning (NUH),
Assoc Prof Shabbir Moochhala (DMRI),
Dr Dietmar Hutmacher (Bioengineering)
Auto Transplantation of Mesenchymal Stem Cell into Chronically
Failing Heart Porcine Model
Principal Investigator
Collaborators
NUH/NUS Clinical Islet Isolation Unit
Faculty of Medicine Research Report 2003
105
: Assoc Prof Eugene Sim
: Assoc Prof Reida El Oakley,
Dr Sunil Rangappa,
Prof Lee Eng Hin,
Assoc Prof Teh Ming
5-azacytindine induced cardiomyocytetransformation of bone
marrow derived mesenchymal stem cells and their therapeutic
potential for the treatment of chronic myocardial infarction
Principal Investigators
Collaborators
: Assoc Prof Eugene Sim,
Dr H K Haider (NUMI)
: Prof Lim Yean Leng,
Mr Ye Lei,
Assoc Prof Liu Teh Chih,
Phillip Wong
Is the Internalization of BCG by bladder cancer cells essential for
successful therapy
Principal Investigator
Collaborator
: Dr R. Mahendran
: Assoc Prof Kesavan Esuvaranathan
Hepatocarcinogenesis secondary to mitochondrial DNA
abnormality in liver cirrhosis
Principal Investigator
Collaborator
: Assoc Prof Leow Chon Kar
: Dr Theresa Tan
The influence of butyrate acid on the muscle differentiation
potential of granulocyte-colony stimulating factor mobilized
human peripheral blood stem cells
Anti-CD154 monoclonal antibody use in conjunction with low
dose immunosuppression in a primate renal allograft model
Principal Investigators
Principal Investigator
Collaborators
Collaborator
: Dr Winston Shim (NCC),
Asoc Prof Eugene Sim
: Assoc Prof Liu Teh Chih
Urine analysis for prognostic indicators of response to therapy
in bladder cancer patients receiving intravesical BCG instillations
Principal Investigator
Co-Principal Investigator
: Assoc Prof Kesavan Esuvaranathan
: Dr R. Mahendran
: Sir Roy Calne
: Assoc Prof John Isaac,
Dr Damian Png,
Dr Hu Huai Zhong
Evaluation of a novel liposomal vector for multiple cytokine gene
therapy in bladder cancer
Principal Investigator
Collaborator
: Assoc Prof Kesavan Esuvaranathan
: Dr R. Mahendran
Transplantation of tissue stem cells from adult bone marrow for
tissue replacement and genetic therapy: an in vivo cellular
alternative to bioengineering and vector mediated gene therapy
A multicenter randomised controlled trial of BCG and IFN-2b in
the treatment of superficial bladder cancer
Principal Investigator
Collaborators
Principal Investigator
Collaborators
: Assoc Prof Reida Oakley
: Dr Lim Sai Kiang (GIS),
Dr Lee Eng Hin,
Dr Ng Soon Chye,
Assoc Prof Teh Ming,
Dr Lim Yean Teng,
Dr Lee Szu Hee,
Dr Manuel Salto-Tellez
Effect of myocardial laser revascularisation and gene therapy on
chronic myocardial ischemia
Percussion, diuresis and inversion therapy assisted passage of
lower pole renal calculi after ESWL
Principal Investigator
Co-Principal Investigator
Collaborator
: Assoc Prof Kesavan Esuvaranathan
: C.W.S. Cheng (SGH),
K. P. Tay (TPH),
P.K. Tan (TTSH),
I. Swaminathan (AH),
Assoc Prof Teh Ming
Principal Investigator
Collaborators
: Dr Edmund Chiong
: Assoc Prof Kesavan Esuvaranathan
: Assoc Prof Li Man Kay
: Assoc Prof Eugene Sim
: Assoc Prof Reida El Oakley,
Dr Jaroslav Hubacek,
Prof Lim Yean Leng (NHC),
Dr Chua Yeow Leng (NHC)
Pathogenesis of post-surgical adhesions and role of phospholipase
A2 and it’s inhibitors in reducing the peritoneal inflammatory
response after surgical trauma
A randomised controlled double-blind trial to determine the
efficacy of orally administered theophylline in assisting the
passage or uteric calculi
Principal Investigator
Co-Principal Investigators
Principal Investigator
Collaborators
Collaborators
: Dr R Mahendran
: Prof P. Gopalakrishnakone,
Dr Charles Tsang (NUH)
: Dr Adrian Ong,
Prof J. Delaney
106
: Assoc Prof Kesavan Esuvaranathan
: Ms Soh Hwei (NUH),
Assoc Prof Li Man Kay
Faculty of Medicine Research Report 2003
The Effect of Chronic Bladder Outlet Obstruction and Spinal Cord
Hemisection on Expression of Neuropeptides and Nitric Oxide
Synthase in the Bladder Wall, Paravesical Ganglia and Spinal Cord
of the Guinea Pig and Human Bladder and Its Relationship to
Detrusor Instability and the Urge Syndrome
Principal Investigators
Collaborators
: Assoc Prof Chin Chong Min,
Dr Damian Png Jin Chye
: Prof Ling Eng Ang,
Dr Chia Seng Joo,
Assoc Prof Li Man Kay
International Publications
Q Wu, R Mahendran and K Esuvaranathan
Nonviral cytokine gene therapy on an orthotopic bladder cancer
model. Clin Cancer Res. 2003; 9(12):4522-8.
J T Schantz, D W Hutmacher, C X Lam, M Brinkmann, K M Wong, T C Lim,
N Chou, R E Guldberg and S H Teoh
Repair of Calvarial Defects with Customised Tissue-Engineered
Bone Grafts II. Evaluation of Cellular Efficiency and Efficacy in
Vivo. Tissue Engineering, S-127 to S-139, 9, Suppl.1 (2003).
J T Schantz, S H Teoh, T C Lim, M Endres, C X E Lam and D W Hutmacher
Repair of Calcarial Defects with Customized Tissue-Engineered
Bone Grafts I. Evaluation of Osteogenesis in a Three-Dimensional
Culture System. Tissue Engineering, S113-126, 9, Suppl.1 (2003).
I J Lim, T T Phan, E K Tan, T T Nguyen, E Tran, M T Longaker, C Song, S T
Lee and H T Huynh
Synchronous activation of ERK and Phosphatidylinositol 3-Kinase
pathways is required for collagen and extracellular matrix
production in keloids. Journal of Biological Chemistry, 278, 42
(2003): 40851-40858.
Liu Qiang, S T F Chan and R Mahendran
E S Tai, A bin Ali, Q Zhang, L M Loh, C E Tan, L Retnam, R M El Oakley,
S K Lim
Hepatic expression of PPARalpha, a molecular target of fibrates,
is regulated during inflammation in a gender-specific manner.
FEBS Lett. 2003; 546(2-3):237-40.
C M Chin, J HU, E A Ling, M K Li and D Png
The effect of chronic bladder outlet obstruction on expression
of nitric oxide synthase in the guinea pig bladder wall to study
its relationship to detrusor instability. European Urology, 1 (2003):
219. (Suppl on European Urology Supplement 2).
C S Chaw, Y Y Yang, I J LIM, T T Phan and N Chung
Water-soluble betamethasone-loaded poly(lactide-co-glycolide)
microparticles as sustained release dosage forms. Effects of
formulation, process types and fabrication conditions on the
performance of microparticles. Journal of Microencapsulation,
20, 3 (2003): 349-359.
J W Chua, Wei Jin and C M Chin
Management of staghorn calculus. Medical Progress, 30, 2 (2003):
28-33.
H K Haider, S Jiang, L Ye, P K Law and E K W Sim
Myoblast transplantation for cardiac repair using transient
immunosuppression. Basic and Applied Myology, 1, 13 (2003):
45-52.
Iyer, Shridhar Ganpathi and C K Leow
Free air or colon? Ann Coll Surg H K, 7 (2003): 136-138.
Faculty of Medicine Research Report 2003
Nitric oxide induces cyclooxygenase expression and inhibits cell
proliferation in colon cancer cell lines. Carcinogenesis,
24, 4 (2003): 637-642.
L Makmur, J Lim and T C Lim
Radiation Therapy In Immediate Breast Reconstruction with Diep
Flap. Plastic and Reconstructive Surgery, 112, 3/CORRESPONDENCE
(2003):920-921.
T T Phan, I J Lim, B H Bay, R Qi, M T Longaker, S T Lee and H Huynh
Role of IGF system of mitogens in the induction of fibroblast
proliferation by keloid-derived keratinocytes in vitro. American
Journal of Physiology-Cell Physiology, 284, 4 (2003): C860-C869.
T T Phan, P See, T N T Nguyen, S T Lee, S Y Chan and H Huynh
Suppression of IGF-1 signaling pathway in keloid-derived
fibroblasts by quercetin: Its therapeutic potential use in the
treatment and/or prevention of keloids. British Journal of
Dermatology, 148, 3 (2003):544-552.
S Ranggapa, Fen Chen, E H Lee, T A Bongso and E K W Sim
Transformation of adult mesenchymal stem cells isolated from
the fatty tissue into cardiomyocytes. Annals of Thoracic Surgery,
75 (2003): 775-779.
E K W Sim, S Muskawad, C S Lim, K H Lim, R T Grignani, J H Yeo, A
Durrani, G Lau and C Duran
A morphological comparison of human and porcine aortic valves.
Clinical Anatomy, 3, 16 (2003): 193-196.
107
J H Sng, A B Ali, S C Lee, D Zahar, J E L Wong, G Cross, V Blake, A Sharif
and P T C Iau
BRCA1 2841/5insA is a recurring mutation with a founder effect
in Singapore Malay women with early onset breast/ovarian cancer.
European Journal of Cancer, 1, (4) (2003): 33.
J H Sng, A B Ali, D Zahar, SC Lee, J E L Wong, V Blake, A Sharif, G Cross
and P T C Iau
BRCA1 c.2845insA is a recurring mutation with a founder effect
in Singapore Malay women with early onset breast/ovarian cancer.
Journal of Medical Genetics, 40, (10) (2003): e117.
H K Tan, T K Y Lee and C H Wang
Simulation of intratumoral release of etanidazole : effect of the
size of surgical opening. Journal of Pharmaceutical Sciences, 92,
4 (2003): 773-789.
H K Tan, F J Wang, T K Y Lee and C H Wang
Computer simulation of the delivery of etanidazole to brain
tumour from PLGA wafer: comparison between linear and double
brust release systems. Biotechnology and Bioengineering, 82, 3
(2003): 278-288.
E K Sim, S Jiang, L Ye, Y L Lim, O C Ooi and H K Haider
Skeletal myoblast transplant in heart failure. J Card Surg. 2003
18(4):319-27. Review.
H K Haider, Y Lei, J Shujia and E K Sim
Cellular myocardial reconstruction using human myoblasts. J Am
Coll Cardiol. 2003 6;42(3):589.
H K Haider, Y Lei, S Jiang, P K Law and E K Sim
Avoiding compliance with histocompatibility dogma using immune
privileged cell xenografts. Ann Thorac Surg. 2003;76(1):
339-40
E K Sim and R T Grignani
Lesser impairment of respiratory function is the mechanism of
faster recovery after partial sternotomy for valve replacement.
Ann Thorac Surg. 2003;75(4):1360.
E K Sim, H K Haider and P K Law
Single fiber skeletal muscle transplantation or purified myoblast
engraftment? J Thorac Cardiovasc Surg. 2003;125(5):1181-2.
W C Ong, S J Lee, M Leow, J Lim, T C Lim and L Makmur
Suction Curettage - Treatment for Axillary Hyperhidrosis and
Hidradenitis. Plastic and Reconstructive Surgery (2003): 958-959.
P S Wong, C K Leow, P S Goh and N Chan
Inferior vena cava leiomyosarcoma. European Journal of Cardiothoracic Surgery, 23 (2003): 241.
J J Wang, C W Ng, Y W Khin, S S Feng, T K Y Lee, C H Wang and
P Shoenmakers
Release of paclitaxel from polylactide-co-glycolide (PLGA)
microparticles and disks under irradiation. Journal of
Microencapsulation, 20 (2003): 317-327.
L Zeng, X Si, W P Yu, H T Le, K P Ng, R M Teng, K Ryan, D Z M Wang,
S Ponniah and D J Pallen
PTP alpha regulates integrin-stimulated FAK autophosphorylation
and cytoskeletal rearrangement in cell spreading and migration.
Journal of Cell Biology, 160, (1) (2003): 137-146.
L Ye, H K Haider, S Jiang, R Ge, P K Law, E K Sim
High efficiency transduction of human VEGF165 into human
skeletal myoblasts: in vitro studies. Exp Mol Med. 2003
31;35(5):412-20.
108
Faculty of Medicine Research Report 2003
Contact Information
Staff Profile
Professor & Head
Associate Professor &
Deputy Head
Professors
:
Soo Khee Chee
:
:
John Isaac
Ti Thiow Kong
Lee Chuen Neng
Sir Roy Calne
(Visiting Professor)
Bernat Soria (Visiting Professor)
Abu Rauff
Alan Porter
Chin Chong Min
Kesavan Esuvaranathan
K. Prabhakaran
Leow Chon Kar
Lim Thiam Chye
Eugene Sim
Wong Poo Sing
Reida Menshawe El Oakley
Timothy Lee
Prema Raj
Hong Ga Sze
Ivor Lim
Mark Da Costa
Edmund Chiong
Jan Thorsten Schantz
Phan Toan Thang
Ratha Mahendran
Dennis Wang
Sng Jen Hwei
Shanmugam Neviliappan
Thomas Yong
Winston Shim
(Honorary appointment)
Lim Hou-Sen (Adjunct)
Hu Jin
Pook Sim Hwee
Damayanti Zahar
Satish Ramapatna L
Wang Xiao Jing
Tham Sin Mun
Lim Yew Koon
Siti Saifa
Wu QingHui
Sriram Ramanan
Lu Yong Jian
Adjunct Professors
:
Associate Professors
:
Adjunct Associate Professors
:
Assistant Professors
:
Senior Research Fellows
:
Research Fellows
:
Research Assistants
:
Faculty of Medicine Research Report 2003
Contact Person
:
Telephone
Email
Facsimile
:
:
:
Contact Person
:
Telephone
Email
Facsimile
:
:
:
Postal Address
:
109
Assoc Prof Kesavan
Esuvaranathan
(Postgraduate/Research
Enquiries)
Department of Surgery
6772-4224
suresuva@nus.edu.sg
6777-8427
Dr R. Mahendran
(Postgraduate/Research
Enquiries)
Department of Surgery
6874-8000
surrm@nus.edu.sg
6777-8427
Department of Surgery
National University of
Singapore
5 Lower Kent Ridge Road
National University of
Singapore
Singapore 119074
INTRODUCTION
Research interests in NUMI are:
cardiovascular research
cancer research
the fundamental issues in pancreatic islet beta-cell biology and with
diabetes related problems
neurodegenerative diseases
A major part of the cardiovascular research is based on human myoblast
and allogenic bone marrow cell transplantation in relation to cellular
cardiomyoplasty in small and large animal models of myocardial infarction.
Myogenic donor cell transplantation for cardiac repair is a potential new
strategy to regenerate irreversibly damaged cardiac tissues and structures.
We have successfully developed pig heart model of myocardial infarction
by coronary artery ligation. We have also created a novel approach to
combine angiogenesis and heart cell therapy for cardiac repair so that
patients do not have to resort to a transplant.
Cancer is the leading cause of deaths in Singapore as well as in the AsiaPacific region. We hope to produce significantly good results within a
relatively short period in Singapore by strengthening the four selected
areas of cancer research (gastric, breast, colorectal, and leukaemia)
where strong researchers already exist in Singapore as well as good
research collaboration in NUS/NUH.
In the year 2003, we received three prestigious awards for our
research achievement:
Prof Yoshiaki Ito is the 12th recipient of the prestigious Tomizo Yoshida
Award in recognition of his discovery of the gene RUNX3, a family of
human cancer genes that could suppress the growth of cancer cells in
the stomach. Ye Lei, a PhD student, received two awards: The Young
Investigator Award 12th International Congress on Cardiovascular Pharm
ISCP-2003, Spain, and National Health Group Young Investigator Merit
Award 2003 (Singapore).
DEPARTMENT OF
National University
Medical Institutes
110
Faculty of Medicine Research Report 2003
RUNX3 in breast cancer
Project Description
Principal Investigator
Collaborators
Grants Awarded in 2003
Molecular mechanism for the activation of Rac1 and downstream
effectors by glucose stimulation in the regulation of insulin
secretion from islet beta-cells
Principal Investigator
Collaborator
: Dr Li Guodong
: Prof Anjan Kowluru
(Wayne State University, USA)
Lipofection of human VEGF165 in human myoblasts for
angiomyogenesis: making it safer for the ailing heart
Principal Investigator
Co-Principal Investigator
Collaborators
: Dr Khawaja Husnain Haider
: Assoc Prof Eugene Sim
: Assoc Prof Teh Ming,
Dr Terrance Chua
(National Heart Centre),
Dr Philip Wong
(National Heart Centre),
Mr Ye Lei
: Dr Lau Quek Choon
: Prof Saraswati Sukumar (Johns Hopkins
University, USA),
Dr Manuel Salto Tellez
The role of aberrant proteolysis in the pathogenesis of acute
promyelocytic leukemia (APL)
Principal Investigator
Collaborator
: Dr Matiullah Khan
: Dr Motomi Osato (IMCB)
Role of RUNX3 as a tumor suppressor in human colorectal cancer
Principal Investigator
: Dr Robert Hewitt
Role of RUNX3 transcription factor in tumor suppression mediated
by TGF-beta
Principal Investigator
: Dr Yasuko Yamamura
Targeting the ER Stress in APL for therapeutic intervention
Principal Investigator
: Dr Matiullah Khan
Establishment of a Gastric Cancer Epidemiology, Clinical and
Genetics Programme
Human skeletal myoblast transplantation for cardiac repair:
molecular basis of donor cell survival and improvement of
myocardial performance
Principal Investigators
Principal Investigator
Co-Principal Investigator
Collaborators
Prospective and retrospective, high-throughput construction of
annotated frozen and Paraffin Tissue Microarrays (TMA) linked
to assessment of histomorphology, immunophenotype and RNA
in-situ Hybridization: Towards the establishment of molecular
information arrays
: Dr Khawaja Husnain Haider
: Assoc Prof Eugene Sim
: Assoc Prof Teh Ming,
Dr Terrance Chua (National Heart Centre)
Genetic influence on prion protein an insight to
neurodegenerative diseases
Principal Investigator
Collaborators
Principal Investigator
: Dr Wong Boon Seng
: Prof Barry Halliwell,
Dr Matt Whiteman
: Assoc Prof Yeoh Khay Guan,
Assoc Prof Laurence Ho,
Prof Yoshiaki Ito
: Dr Manuel Salto-Tellez
Ongoing Projects
Growth and apoptosis of islet beta-cells during depletion of
cellular GTP by inhibition of IMP dehydrogenase
Principal Investigator
: Dr Li Guodong
Crossing the histocompatibility barriers using transient
immunosuppression: implications in cellular cardiomyoplasty
using human skeletal myoblasts for cardiac repair
Principal Investigator
Collaborators
Point mutations in Runx 1 found
in leukemia patients (red)
Faculty of Medicine Research Report 2003
111
: Dr Khawaja Husnain Haider
: Dr Lim Yean Leng
(National Heart Centre),
Assoc Prof Teh Ming,
Dr Philip Wong
(National Heart Centre),
Mr Ye Lei
H K Haider, S J Jiang, L Ye, P K Law and E K W Sim
International Publications
Myoblast transplantation for cardiac repair using transient
immunosuppression. Basic & Appl Myology 2003, 13: 45-52.
J Huo, S A Metz and G D Li
E K W Sim, H K Haider and P K Law
Role of tissue transglutaminase in GTP depletion induced apoptosis
of insulin-secreting (HIT-T15) cells. Biochem. Pharmacol 2003,
66, 213-223
Single skeletal muscle transplantation or the purified myoblast
engraftment. J Thoracic Cardiovasc Surgery 2003, 125: 118-82.
E K W Sim, L Ye, S J Jiang, Y L Lim, O C Ooi and H K Haider
R Amin, H Q Chen, J Li, G D Li and A Kowluru
Mastoparan-induced insulin secretion from insulin-secreting
clonal ß [ßTC3 and INS-1] cells: Evidence for its regulation via
activation of Rac, a small molecular weight GTP-binding protein.
Endocrinology 144, 4508-4518
J Huo, S A Metz and G D Li
p53-independent induction of p21Waf1/Cip1 contributes to the
activation of caspases in GTP-depletion induced apoptosis of
insulin-secreting cells. Cell Death Differ. (published online Sep
12, 2003)
L Ye, H K Haider, S J Jiang, P K Law and E K W Sim
High efficiency transduction of humanVEGF165 into human
skeletal myoblast cells: in vitro studies. Exp Mol Medicine 2003,
35(5), 412-20.
L Ye, H K Haider, C S Wang, Z Q Cheng, H Chen, K J Hu and Q Zhao
Dose dependent effect of aprontinin on aggravated proinflammatory cytokines in patients with pulmonary hypertension
following cardiopulmonary bypass. Cardiovascular Drugs and
Therapy, 2003, 17: 343-48.
Skeletal myoblast transplant in heart failure. J Cardiac Surg 2003,
18: 319-327.
H K Haider, L Ye, S J Jiang, P K Law and E K W Sim
Avoiding compliance with histocompatibility dogma using immune
privileged cell xenografts. Annals Thoracic Surgery 2003, 337:
339-340.
H K Haider, L Ye, S J Jiang and E K W Sim
Cellular myocardial reconstruction using human myoblasts. J Am
Coll Cardiol 2003, 42: 589.
S J Jiang, H K Haider, L Ye, M Teh, G Fang, T Chua, P K Law and
E K W Sim
Xenotransplantation of human skeletal myoblasts shows longterm survival in a porcine heart. ASEAN Heart J 2003, 10: 31-36.
L Ye, H K Haider, S J Jiang, H L Lieng, N M Idris, R A Jalil, P K Law and
E K W Sim
Angiogenesis using human myoblast carrying human VEGF165
for injured heart. Annals Acad Med Singapore, 2003: 32(5):
S21-S23.
C K Kim, E J Choi, S H Choi, J S Park, H K Haider and Ahn W S
H K Haider, S J Jiang, S Aziz, L Ye, P K Law and E K W Sim
Enhanced p53 gene transfer to human ovarian cancer cells using
the cationic non-viral vector, DDC. Gynecol Oncol 2003, 90(2):
265-72.
Effectiveness of transient immunosuppression using cyclosporine
for xenomyoblast transplantation for cardiac repair. Exp Clinical
Transplant 2003, 1: 27-28.
Mr Ye Lei who received two prestigious awards for his research achievement
& his team
112
Mechanism of unfolded protein response
(UPR) induced by PML-RAR in Acute
Promyelocytic Leukemia (APL)
Faculty of Medicine Research Report 2003
Oncology Research Institute
Y Ito and K Miyazono
RUNX transcription factors as key targets of TGF-beta superfamily
signaling. Current Opinion in Genetics & Development 13, 4347.
K Döhner, K Tobis, T Bischof, S Hein, R F Schlenk, S Fröhling, H Döhner,
B U Mueller, T Pabst, M Osato, N Asou, L M Johansen, T Dayaram,G
Behre, W Hiddemann, Y Ito, D G Tenen
Mutation analysis of the transcription factor PU.1 in younger
adults (16 to 60 years) with acute myeloid leukemia: a study of
the AML Study Group Ulm (AMLSG ULM) Blood 102: 3850 – 3851
B U Mueller, T Pabst, M Osato, N Asou, L M Johansen, M D Minden, G
Behre, W Hiddemann, Y Ito and D G Tenen
J Harada, K Kokura, C Kanei-Ishii, T Nomura, M M Khan, Y Kim, S Ishii
Requirement of the co-repressor HIPK2 for Ski-mediated inhibition
of BMP-induced transcriptional activation. J Biol Chem. 2003 Jul
21 PMID: 12874272
K Kokura, H Kim, T Shinagawa, M M Khan, T Nomura, S Ishii
The Ski-binding protein C184M negatively regulates tumor growth
factor-b signalling by sequestering the smad proteins in the
cytoplasm. J Biol Chem. May 30 278 (22): 20133-20139.
M P Hande, T V Azizova, C R Geard, L E Burak, C R Mitchell, V F
Khokhryakov, F K Vasilenko and D J Brenner
Past exposure to densely ionizing radiation leaves a unique
permanent signature in the genome. American Journal of Human
Genetics 72 (5): 1162-1170.
Heterozygous PU.1 mutations are associated with acute myeloid
leukemia. Blood 101:2074
J Abraham, B Lemmers, M P Hande, M E Moynahan, C Chahwan, A Ciccia,
J Essers, K Hanada, R Chahwan, A K Khaw, P McPherson, A Shehabeldin,
R Laister, C Arrowsmith, R Kanaar, S C West, M Jasin, R Hakem
K Inoue, S Ozaki, K Ito, T Iseda, S Kawaguchi, M Ogawa, S C Bae, N
Yamashita, S Itohara, N Kudo and Y Ito
Eme1 is involved in DNA damage processing and maintenance
of genomic stability in mammalian cells. EMBO Journal 22:
6137-6147.
Runx3 is essential for the target-specific axon pathfinding of
trkC-expressing dorsal root ganglion neurons. Blood Cells,
Molecules & Diseases. 30, 157-160
S C Bae and Y Ito
Comment on Levanon et al., Runx3 knockouts and stomach cancer.
EMBO reports 4:6
M P Hande
DNA repair factors and telomere-chromosome integrity
in mammalian cells Cytogenetic and Genome Research
(Invited Review; in press).
M Matsuno, M Osato, N Yamashita, M Yanagida, T Nanri, T Fukushima,
Y H Wang, S Kusumoto, M Towatari, R Suzuki, T Naoe, K Nishii, K
Shigesada, R Ohno, H Mitsuya, Y Ito and N Asou
Dual mutations of the AML1 and FLT3 genes in patients with
acute myeloblastic leukemia of the M0 subtypes. Leukemia 17,
2492-2499
T Yoshida, H Kanegane, M Osato, M Yanagida, T Miyawaki, Y Ito,
K Shigesada
Functional analysis of RUNX2 mutations in cleidocranial dysplasia:
novel insights into genotype-phenotype correlations. Blood Cells,
Molecules & Diseases. 30, 184-193
S T Fraser, M Ogawa, T Yokomizo, Y Ito and S Nishikawa
Putative intermediate precursor between hematogenic endothelial
cells and blood cells in the developing embryo. Developmental
Growth & Differentiation 45, 63-75.
Faculty of Medicine Research Report 2003
113
Staff Profile
Professor and Director
Associate Professor &
Deputy Director
Professor and Director (ORI)
Senior Research Scientists
:
Yap Hui Kim
:
:
:
Research Scientists
:
Research Fellows
:
Research Assistants
:
Shazib Pervaiz
Yoshiaki Ito
Wong Boon Seng
Richie Soong Chuan Teck
Yasuko Yamamura
Li Guodong
Khawaja Husnain Haider
Lee Shao Chin
Lilia Kuleshova
Huang Canhua
Ko Tun Kiat
Lau Quek Choon
Matiullah Khan
Huang Liqun
Liu Qiang
Rudaba Nasreen Akhand
Huo Jianxin
Li Jingsong
Goh Wee Kee
Anuradha Poonepalli
Contact Information
Contact Person
Telephone
Facsimile
Email
Postal Address
:
:
:
:
:
Homepage
:
Contact Person
Telephone
Facsimile
Email
Postal Address
:
:
:
:
:
Ms Tan Bee Lay
6874-8098
6773-5461
nmisec@nus.edu.sg
National University
Medical Institutes
Blk MD11 10 Medical Drive
#02-01 Clinical Research Centre
Singapore 117597
http://numi.nus.edu.sg
Ms Selena Gan
6874-1873
6773-5461
nmigans@nus.edu.sg
Oncology Research Institute
National University
Medical Institutes
Blk MD11 10 Medical Drive
#03-01C Clinical
Research Centre
Singapore 117597
114
Faculty of Medicine Research Report 2003
AWARDS & PRIZES
Faculty Of Medicine Research Report 2003
AWARDS & PRIZES
Ms Sharon Thio
Anatomy
won the Merit Award, Basic Science Poster Contest at the 4th Combined
Scientific Meeting (Life Sciences in Singapore : Integrating Multidimensional
Perspectives in January 2003.
Dr Yip Wai Cheong
A*STAR International Fellowship. Awarded by the Biomedical Research
Council, A*STAR.
Microbiology
Zou X, Foong KWC, Yip GWC, Cao T, Bay BH and Ouyang HW
Best Oral Science Award - 7th NUS-NUH Annual Scientific Meeting.
“The effect of heparin sulfate and chondroitin sulfate on palatal
fibroblast activities”.
Assoc Prof Vincent T. K. Chow
Prof P Gopalakrishnakone
Koh Wee Lee
was awarded the Faculty Research Excellence Award 2002-2003.
was awarded the Excellent Award Travel Scholarship for the 6th AsiaPacific Congress of Medical Virology, December 2003.
Biochemistry
Chan Yow Cheong Oration, 6th Asia Pacific Congress of Medical Virology,
December 2003.
Obstetrics & Gynaecology
Prof Barry Halliwell
has again been named by ISI as one of the world’s most cited scientists
in Biology and Biochemistry, ranked in the top 30 out of 5724 worldwide.
COFM
Dr Koh Woon Puay
was awarded the Avon Foundation-AACR International Scholar-in-Training
Award for the AACR 94th Annual Meeting, 2003.
Dr Annelies Wilder-Smith
was awarded the Best Oral Presentation Award at the 9th International
Conference on Travel Medicine, New York held from 7-11 May 2003.
Prof Ariff Bongso
was presented the Excellence for Singapore Award in May 2003 for his
work in assisted reproduction and stem cell biology, which makes Singapore
a centre of medical excellence. He was also awarded the Fellowship (ad
eundem) of the Royal College of Obstetricians & Gynaecologists in
September 2003 acknowledging his major contributions to the well being
of women.
Dr Chong Yap Seng, Dr Su Lin Lin and Dr Samuel M
were the recipients of the Best Free Paper Oral Presentation Award
for the article ‘The Use of Misoprostol Administered by Different
Routes to Prevent Postpartum Haemorrhage: A Systematic Review’
by the International Conference on Evidence-Based Medicine 2003 in
October 2003.
Dr WH Chua, Assoc Prof SM Saw and Assoc Prof D Tan
SC Ng, YS Chong, M Rauff, Myo ZM, C Nurfarah, SSL Chew, M
Yap, PRM Deurenberg
were awarded the Young Investigator Award – Outstanding (Clinical) at
the First SERI-ARVO Meeting on Research in Vision and Ophthalmology,
Singapore 2003 for the paper “Refractive errors and their correction in
Singapore school children”.
were presented the 11th Asian Congress of Pediatrics Award for the
article ‘The influence of breast compared to formula feeding on infant
adiposity – A prospective pilot study’ by the Asian Congress of Pediatric
on 7 November 2003.
Choolani M, Kumar S, O’Donnell H, O’Donoghue K, Campagnoli
C, Talbert D, Roberts I, Bennett PR, Fisk NM
Medicine
Assoc Prof Kong Hwai Loong
was listed in The Peak’s ‘The Who’s Who of Singapore’, Second Edition.
Dan Y Y
was awarded the A*STAR scolarship to go Seattle to study Fetal liver
Stem Cells.
116
were the recipients of the Best Oral Presentation in Obstetrics for the
article ‘Primitive fetal erythroblasts: ideal target for 1st trimester noninvasive prenatal diagnosis.’ in the 4th Singapore Congress in O&G/1st
Singapore-Malaysian Conference in O&G, Sheraton Towers Hotel,
Singapore, 16-19 January, 2003.
Loy Chong Jin
won the Young Scientist of the year at the 7th NUS-NUH Annual Scientific
Meeting (in conjunction with GIS, IMCB and JHS) held in 2003.
Faculty of Medicine Research Report 2003
Gong Yin Han, Lim Lis Sa Elissa, Loy Chong Jim, Obbard Jeffery,
Stephane Bayen, Yong Eu Leong
won the Best Clinical Science Poster Award for the article “Screening for
endocrine-disrupting compounds in mussel and phytoplankton with sexhormone receptor driven reporter gene bioassays and LC-MS and CEMS” at the 7th NUS-NUH Annual Scientific Meeting (in conjunction with
GIS, IMCB and JHS) held in 2003.
Lim Lis Sa Elissa, Gong Yin Han, Chin Hong Soon, Loy Chong
Jim, Obbard Jeffery, Yong Eu Leong
won the Best Clinical Science Poster Award (Merit) for the article “Sex
hormone disruptors in Singapore’s marine environment” at the 7th NUSNUH Annual Scientific Meeting (in conjunction with GIS, IMCB and JHS)
held in 2003.
Ophthalmology
Dr Wong Tien Yin
was awarded the Ethicon Foundation Travel Grant by Royal College of
Surgeons of Edinburgh, UK.
Orthopaedic Surgery
Teo Yee Hong, Dr Li Li, Dr James Hui, Prof Lee Eng Hin
Young Doctor Award. A comparative study of efficacy of mesenchymal
stem cells (MSC) from bone marrow, periosteum and fat transfers in the
treatment of partial growth arrest at the 7th NUS-NUH Annual Scientific
Meeting, 2-3 October 2003.
Andrew Dutton, Dr James Hui, Prof Lee Eng Hin
Young Orthopaedic Investigator Award. Enhancement of meniscal
regeneration using mesenchymal stem cells in a porcine model at the
Annual Scientific Meeting of the Singapore Orthopaedic Association, 2528 November 2003.
Byers Benjamin A, Guldberg Robert E, Hutmacher Dietmar W,
Garcia Andres J
First Prize, Oral Presentation in PhD category. Runx2 Genetic Engineering
Enhances In Vitro and In Vivo Mineralization in Fused Deposition-Modeled
Polycaprolactone Tissue-Engineered Scaffolds at the 6th Annual meeting
of the Tissue Engineering Society International , 10-13 December 2003.
Dr Wong Tien Yin
Otolaryngology
was awarded Young Scientist of the Year Award (Finalist) by National
Academy of Science, Singapore.
Dr Wong Tien Yin
Dr Wang De Yun
was awarded the BMRC Young Investigator Award for his remarkable
contribution to research in Singapore.
received 2003 Sam Sanders Award for Basic Science from the American
Academy of Otolaryngic Allergy (AAOA).
Dr Wong Tien Yin
Paediatrics
was awarded the Outstanding Service in Prevention of Blindness by the
Asia Pacific Academy of Ophthalmology (APAO).
Dr Wong Tien Yin
Dr Allen Yeoh, Prof Wong Lim Soon, Dr Li Jinyan, Ms Liu Huiqing
was awarded the Faculty Research Excellence Award 2002-2003.
Dr Leonard Ang
was awarded The Asian Innovation Awards - GOLD MEDAL by the Far
Eastern Economic Review (FEER) and the Singapore Economic Development
Board.
Best Free Paper (2nd) - 14th Singapore General Hospital Annual Scientific
Meeting 2003.
Dr Lee Yung Seng
Dr Leonard Ang
Young Investigator Award - 14th Singapore General Hospital Annual
Scientific Meeting 2003.
Dr Aung Tin
was awarded The Eye Institute-Pfizer Research Prize for Best Original
Paper for his paper ‘Additive effect of unoprostone and latanoprost in
patients with elevated intraocular pressure.’
Faculty of Medicine Research Report 2003
AFES Young Investigator Award
“Prevalence of Melanocortin-3 Receptor (MC3R) and Melanocortin-4
Receptor (MC4R) Gene Mutations in Obese Singapore Children”. ASEAN
Federation of Endocrine Societies (AFES) 12th Congress of ASEAN
Federation of Endocrine Societies, 30 Nov - 4 Dec 2003, Singapore.
Felicia Cheah Siew Hong
Poster Merit Award - 4th Combined Scientific Meeting. “The zebrafish
Danio rerio as an animal model for craniofacial development and disease
- genomic and functional studies of tgfß3”.
117
Arnold Tan Sia Chye
2nd Prize Poster Award - 4th Singapore Congress in O&G and 1st
Singapore-Malaysia Conference in O&G (O&G Society). “Validation of a
single cell polymerase chain reaction (PCR) assay for application to
preimplantation genetic diagnosis (PGD) of hemoglobin (Hb) Bart's
hydrops fetalis syndrome".
Dr Dawn Lim Li Chern
Psychological Medicine
Dr Tan Hao Yang
won the American Psychiatric Institute for Research and Education –
Astra Zeneca Young Minds in Psychiatry Award for Schizophrenia Research
(International Category) in May 2003.
was awarded the American Academy of Allergy, Asthma and Immunology
(AAAAI) International Travel Grant Award 2003
Surgery
Zhao Ziqing, Priya Kadam and Dr Lai Poh San
Finalist in the Singapore Science and Engineering Fair 2003. “Single
nucleotide polymorphisms analysis of RB1 gene in Four Asian Populations”.
Dr Lai Poh San, Low Swee Ling, Khng Hwee Hoon, Prof Low
Poh Sim
Amersham Biosciences Best Presentation Award at the 4th Combined Life
Sciences Conference in Singapore: Integrating Multidimensional
Perspectives, 15-18 January 2003, Faculty of Medicine, Singapore
Pathology
Dr Ye Lei
Young Investigator Award
12th International Congress on Cardiovascular Pharmacotherapy held in
Spain in 2003.
Dr Zhang Zhijiang
was awarded a travel award to present his work at the American Society
of Gene Therapy Annual Meeting held in Washington DC in 2003.
Dr Sng Jen-Hwei
Dr Tan Kong Bing, Ms Vanessa Soh, Dr Thomas P Thamboo, Ms
Barbro Nilsson, Dr Satina Chang and Dr Norman Chan
were awarded the Royal College of Pathologists of Australasia Quality
Assurance Programs Trainee Poster Prize during the Pathology Update
of the Annual Scientific Meeting, Royal College of Pathologists of
Australasia, Sydney, Australia, March 2003 for their Poster Presentation.
Title: "Quality indices in a cervicovaginal cytology service: pre and postlaboratory accreditation".
Dr Tan Kong Bing, Ms Lim Hui Qin, Mr Winston Wu and Dr
Norman Chan
vwere awarded the Best Poster Award (Medicine/Paediatrics) during the
National Healthcare Group 2nd Annual Scientific Congress in October
2003, Singapore. Title: "Cell block immunocytochemistry helps in the
differentiation between adenocarcinomas and mesotheliomas".
won the award for the best oral presentation– Surgery/Obstetrics &
Gynaecology/Dentistry at the National Healthcare Group Annual scientific
meeting held in 2003.
Dr Wu Qinghui
won a merit award at the 7th NUS-NUH Annual Scientific Meeting held
in 2003.
Ms Seow Shih Wee
won the fourth prize in the 3rd Annual Graduate Student Society-Faculty
of Medicine Sci Conference held in 2003.
Dr Liu Qiang, Dr Wu Qinghui, Dr Zhang Zhijiang and Ms Seow
Shih Wee
were awarded travel awards by the Sir Edward Youde Memorial Fund to
attend a postgraduate conference in Hong Kong in 2003.
Ms Chiu Lily, Ms Leow Gek Har, Assoc Prof Vincent T K Chow,
Assoc Prof Paul A Tambyah and Assoc Prof Evelyn S C Koay
were awarded the 6th APCMV Excellence Award at the 6th Asia Pacific
Congress of Medical Virology, 7–10 December 2003, Kuala Lumpur,
Malaysia. Title: “The use of an in-house RT-PCR assay for dengue virus
detection in the differential diagnosis for patients with possible SARS”
Physiology
NUMI
Dr Ye Lei
Young Investigator Award
12th International Congress on Cardiovascular Pharmacotherapy held in
Spain in 2003.
Dr Ye Lei
National Health Group Young Investigator Merit Award 2003 (Singapore).
Dr M. Prakash Hande
was awarded the UICC Yamagiwa-Yoshida International Cancer Study
Grant by International Union Against Cancer (Union Internationale Contre
le Cancer), Geneva, Switzerland.
118
Prof Yoshiaki Ito
Was awarded The Tomizo Yoshida Award for his work in RUNX genes in
Nagoya, Japan, September 2003.
Faculty of Medicine Research Report 2003
PATENTS
Faculty Of Medicine Research Report 2003
PATENTS
Anatomy
Paediatrics
Suresh C Srivastava, Satya P. Bajpai. Kwok-Hung Sit
Heng Chew Kiat, Javier Cabrera, Tham Chen Khong
1.
Methods for assessing risk of diseases with multiple contributing factors
CpG Oligonucleotides as a carrier of drug-gemcitabine-CpG
oligonucleotides as highly promising anticancer agents.
2. Oligonucleotides and intermediaries.
Applicant: ChemGenes Corp. Wilmington, MA. National University of
Singapore; Application number: Transmittal Express Mail No.
ER220423975US, Transmittal Express Mail N. EU067835608US; Filed on
July 16, 2003
Biochemistry
Chua Kaw Yan, Cheong Nge, Lee Bee Wah
Novel therapeutic molecules and uses therefore. Filed on February 2003
Chua Kaw Yan, Cheong Nge and Lee Bee Wah
The use of a fungal immunomodulatory protein, Fve, for immunotherapy,
against allergy, virus infection and cancer. INTRO Ref: CHUA KY 03-UK.
Filed on 16 April 2003
Miao Yubo, Chen Yu, Lim Tit Meng, Heng Chew Kiat
Too HP., Anwar, A. and August, JT.
Specific Detection and Quantification of the Replicative Forms of the RNA
Virus by Fluorescence-based PCR, USSN- 60/408,818.
Shallow multi-well plastic chip for thermal multiplexing. US Provisional
Application No. : 60/456, 929. Filed on 24 March 2003. US Application
No. : 10/613, 599 filed on 3 July 2003
Victor Samper, Ji Hong Miao, Chen Yu, Heng Chew Kiat, Lim
Tit Meng
Microbiology
Nucleic Acid Purification Chip. US Provisional Application filed on 30
December 2003.
Ho Bow
A novel generation of cloned horseshoe crab recombinant Factor C for
detection and removal of endotoxin (United States Patent Application
No. 6, 645, 724, 11 Nov 2003).(European Patent Office Patent Application
No. 98 945 748.6)
Mary Ng Mah Lee and Justin Chu Jang Hann
Interaction between cell receptor protein and flavivirus attachment
domain/s and uses thereof. U.S. Provisional Application no. 60/442,517,
filed on January 22, 2003
Chan Soh Ha, Leung Pak Hing, Song Yong Cheng
Gold Drug A - Effective anti-cancer agent shown in vitro and in vivo. US
Patent No. 2003/0114695 A1
Pharmacology
Zhu Yi Zhun
Anti-anxiety effects of Salviae Miltiorrhizae in the treatment of
anxiety/fear. (China)
Brett P. Monica, William A. Gaarde, Pamela Nero, Robert Mckay,
W.S. Fred Wong
Antisense modulation of p38 mitogen-activated protein kinase expression.
PCT International Application (USA)
Sim Meng Kwoon
Use of angiotensin I derivative as an agent for the treatment and prevention
of glomerulosclerosis and renal failure (USA).
Obstetrics & Gynaecology
P. Gopalakrishnakone, XC Pu, PTH Wong, MCE Gwee
and RM Kini
Yong EL, Yap SP.
Methods for preparing an estrogenic preparation and isolated estrogenic
compounds from a plant and uses thereof. US Patent No: 2003/0170292
A1. Published: September 11 2003. Published on-line
Yong EL, Lim ELS
Butler M. Method for the preparation of phytoprogestogenic extracts
from rhizoma ligusticum chuanxiong and uses thereof. US and PCT
application no. PCT/SG03/00195, Intro Ref: Yong el 03 – PCT. Filed on 29
August 2003.
Therapeutic molecules derived from snake venom. (USA)
Physiology
William Harnett, Margaret M. Harnet, Ian B. McInnes, Charles
McSharry, Alirio J. Melendez
Es-62 for asthma. New British Patent Application No. 0322186.8 Surgery.
Yong EL, Ng Toon Yaa, Shen Ping, Heng WS, Gong Yin Han
Compositions and method for treatment of steroid/nuclear receptor mediated diseases. US Regular Patent Application. Intro ref. Yong EL 04.
Filed on 2 December 2003
Surgery
Teoh Swee Hin, Ten Kim Cheng, Dietmar Hutmacher, Lim Thiam
Chye, Jan-Thorsten Schantz and Chou Ning
Bioabsorbable plug implants and methods for bone tissue regeneration.
Place of registration: US
120
Faculty of Medicine Research Report 2003
GRADUATE STUDENTS
Faculty Of Medicine Research Report 2003
GRADUATE STUDENTS
Thesis Passed
Bai Jing
Anaesthesia
Drug metabolism and transport in cirrhotic liver.
Edula Goutham
Hepatitis B database.
MSc
Kunde Ramamoorthy Govindarajan
Helen Isaac
MHC - peptide interaction studies using Bioinformatic tools.
Cytokine changes in traumatic brain injury.
Lee Tien Huat
Shalini Girotra
Heat shock proteins as cancer vaccines.
The role of acupuncture in the treatment of neck pain.
Li Hongzhe
Genetic epidemiology of coronary artery disease: Polymorphic studies
of ACATZ.
PhD
Sethuraman Rama
Li Kai
Isolation and characterization of new peptides from human cerebrospinal
fluid (CSF).
Development of computational methods for the rapid determination of
NMR resonance assignment of large proteins.
Li Xiaolei
Structure and function studies of snake toxin.
Anatomy
Ren Jihui
Analysis of membrane tracfficking in ncr-yeast strains.
MSc
Shanmugasundaram Deivanayagam
Roles of aquaporins in normal and preelamptic placenta.
Kok Yee Jiun
Control of FAS-mediated apoptosis in glioma cells.
Shen Yiru
Studies of site-directed mutagenesis of CD38 in CHO cell lines.
Sathiyamoorthy Selvarajan
C-erb B2 expression in invasive breast cancer in Singapore women.
PhD
PhD
Liang Fubo
Functional Studies of CD157-mediated Tyrosine Kinase Signalling.
Nirthanan Selvanayagam
Biological activity of venoms and toxins from some snakes from Sri Lanka.
COFM
Thirumangalathu Shoba
Neurogenesis and retinoic acid induced changes in the cardiac ganglionic
cells of the developing rat heart.
MSc
Wang Xu
Neurodegeneration and glial cell reactions in the visual system of the rat
following experimentally-induced glaucoma.
Chen Jing
C Ananth
Alcohol drinking and coronary heart disease mortality in
Singapore Chinese.
Neurotoxic effects of domoic acid in rats.
Manoj Kumar Singh
Review of acute pancreatitis patients in a tertiary hospital in Singapore.
Biochemistry
M Med (OM)
MSc
Thio Yauw Leng Bernard
A survey of dermatological conditions in a pharmaceutical plant in
Singapore.
Anita Suresh
Biocomputing for database construction, data mining, molecular modelling.
Reynold Ofanoa
Occupational health and safety priority areas in the Kingdom of Tonga.
122
Faculty of Medicine Research Report 2003
Ms Kuay Kuee Theng
Physiology
Catalogue of the expressed genes of the major allergen producing dust
mite, Biomia Tropicalis
Ms Tan Teng Nging
MSc
Epidemiology of allergic respiratory diseases in preschool children
in Singapore.
AKM Sanual Haq Chowdhury
Ms Wong Fei Ling
To study the mechanism of chemotherapeutic activity of resveratrol
Immunochemical characterization, identification and cloning of novel
allergens from fungus, curvularia lunata.
Surgery
Ms Yang Li
Characterization of Blo t3, a novel group 3 allergen from house dust
mites Blomia tropicalis.
PhD
Ms Zhang Yujing
Clinical profile of infants and children with congenital heart disease in
National University Hospital.
PhD
Dr RL Satish
Pathogenesis of postsurgical adhesions in the presence of physical barriers
and phospholipase a2 inhibitors.
Dr Pook Sim Hwee
Mechanisms of BCG immunotherapy
Mr Kuo I-Chun
Development of therapeutic and diagnostic reagents for allergic diseases.
MD
MD
Dr Aamir Hassan Sheikh
Assoc Prof Quek Swee Chye
Role of p38Map kinase in colorectal cancer
Haemostatic profile and coronary risk in Singapore newborns and their
molecular control.
Dr Anil Kumar
Pharmacology
MSc
Role of S100A4 in colorectal cancer metastasis
Dr Zhang Zhijiang
Intravesical TNF- gene therapy mediated by a novel liposome system in
an orthotopic murine bladder cancer model.
Dr Zhang Li
Therapeutic angiogenesis by gene therapy
Ji Xinyan
A comparative study of the cardioprotective effects of salvia miltiorrhiza
and ramipril after acute myocardial infarction in rats.
NUMI
Xu Chengyu
Effects of angiotensin IV on cardiac hypertrophy in rats and
rat cardiomyocytes.
PhD
Vanaja Manivasager
Huo Jianxin
Photodynamic diagnosis of neoplasms using the novel photosensitizer,
protoporphyrn IX.
Mechanisms of GTP-depletion induced apoptosis in HIT-T15 insulin
secreting cells.
PhD
Mr B. Chowbay
Pharamacogenetics of ABC transportors and drug metabolising enzymes
and the influence of SNPs on irinotecan (CPT-II) disposition in
nasopharyngeal carcinoma patients.
Faculty of Medicine Research Report 2003
123
Kalpana Ramnarayanan
MD
Mucin binding of Helicobacter pylori.
Lim Chai Yen
Chan Leung Kwok, Clement
Epigenetic analysis and pharmacological manipulation of the major latent
promoter W of Epstein Barr virus.
Duplex ultrasound penile blood flow study and lipid profile to differentiate
psychogenic from arteriogenic causes of erectile impotence.
Shirley Ting Hui Ling
Seroepidemiology of Japanese encephalitis virus in the human and animal
population in Singapore.
Ophthalmology
PhD
MSc
A.M.A. Nasirudeen
Luo HaiDong
Cellular and Cytochemical characterization of programmed cell death in
the protozoan parasite Blastocysis hominis.
Corneal Curvature and Myopia: A Cross Sectional Study in Singapore
School Children.
Chan Wai Ping Marieta
Sun XiaoYin
Identification of natural mutants of the hepatitis B virus enhancer II
affecting viral replication.
Analysis of PCR-Base Detection of Microorganisms Causing Severe
Ocular Infections.
Jeanette W.P. Teo
PhD
Genetic determinants of antibiotic resistance and virulence factors in
Vibrio harveyi.
Wu Hui Min
Li Bin
Genetic Epidemiology of Myopia
Delaying lymphocyte homing in the prevention of murine graft-versushost disease.
Orthopaedic Surgery
Lim Kah Meng
Genomic mapping, localization and functional analysis of the novel human
DENN gene.
MSc
Lim Tok Hoon
Development of biological processes for the treatment of oily wastewaters
and sludge and a feasibility study on in situ bioremediation of a
hydrocarbon contaminated aquifer.
Moe Maung Maung
The natural history of adolescent idiopathic scoliosis in Singapore
school children
Sunita Singh
PhD
Molecular typing of eneteroviruses and development of a DNA vaccine.
Ouyang Hongwei
Obstetrics & Gynaecology
Tissue engineering approach for tendon/ligament repair and regeneration
MSc
Paediatrics
Mid-trimester uterine artery Doppler screening as a prediction of adverse
pregnancy outcome in unselected women.
MSc
Sabina Islam
Ms Chew Joon Lin
PhD
In vivo evaluation of chitosan nanoparticles for the delivery of mite
allergen genes and proteins in mice.
Lim Po I, Joyce
Ms Hon Sook Mei
The androgen receptor and infertility.
Characterization of the allergenic components of the pollen of oil palm,
Elaeis guineensis Jacq. (Arecaceae)
Kalamegam Gauthaman
Effect of tribulus terrestris I. on male reproductive function
124
Faculty of Medicine Research Report 2003
Chiam Tut Fu
Medicine
Intrinsic risk factors for musculoskeletal injuries amongst Basic Military
Training Recruits.
Andijani Maria Ratna
MSc
Noise induced hearing loss in a pulp and paper mill, Riau, Indonesia.
Lim Hung
Occupational deafness compensation in Hong Kong 1995-2002: Profile
and rates of compensated hearing loss.
Dr Cho Cho Myint
Hussain Altaf
The relationship of ascorbic acid intake and serum ascorbic acid with
nutritional parameters in chronic ambulatory peritoneal dialysis (CAPD)
patients.
Prevalence of bronchial asthma among workers of a fertilizer factory.
Zhang Xiaozhu
M Med (PH)
The polymorphisms of the high affinity immunoglobulin E receptor beta
chain, beta-2 adrenergic receptor, platelet activating factor acetylhydrolase
genes and asthma in Singapore.
Ong Pang Yeow, Gary
Zaw Min
Cohort study on factors affecting breastfeeding duration in Singapore.
Management of pain in the Emergency Department.
Genetic polymorphisms of major histocompatibility complex class II (MHC
Class II),apoliprotein H (APOH) and angiotensin-converting enzyme (ACE)
genes in patients with the antiphospholipid syndrome: Association with
anti-beta2-glycoprotein I antibodies in 3 ethnic groups.
Shyamala Thilagaratnam
Daw Mya Mya
Follow-up after screening for scoliosis – does it make a difference?
Predictors for 30-day and one-year mortality outcome undergoing primary
angioplasty for acute myocardial infarction.
Lim Ghee Hian
Teoh Yee Leong
A survey of the social-economic status of patients from the National
Healthcare Group Polyclinics, Singapore.
Zhang Weidong
Polymorphisms of the candidate genes IL4R, IL4 and TNF-a for asthma
in Asian populations.
Paul Chang Yoong Ming
Career preferences of Singapore-trained final-year medical students and
house officers in 2003.
Sonia Baig
Airways cellular response in near-fatal asthma with or without association
of respiratory viruses.
Mukherjee Karabee
Delayed childbearing- are there any risks? A hospital based study
in Singapore.
Jin Aizhen
Adherence to and efficacy of an evidence based management algorithm
for acute asthma in the emergency department.
Anie Haryani Abdul Rahman
Barriers to good glycaemic control among patients with type 2 diabetes
in Brunei Muara District, Brunei Darussalam: patients’ perspectives.
MD
Ananda Raj
Dr Chiew Yoke Fong
The prevalence of pulmonary tuberculosis in Taiping, Malaysia.
The epidemiology and laboratory detection of resistant enterococci.
Leung Wai Man Raymond
Impact Evaluation of food safety programme: control of clenbuteroltainted pig’s products in the Hong Kong Special Administrative
Region (HKSAR).
Microbiology
Tsui Lok Kin Edwin
PhD
The epidemiology of chickenpox in the Hong Kong Special Administrative
Region (HKSAR) (1989-1993 and 1999-2001).
Chua Jia En, John
PhD
Interactions between dengue virus non-structural proteins with host
cellular proteins.
Niti Muhamad
Devipriya Subramaniyam
Amenable mortality and avoidable hospitalization: Using populationbased outcome indicators for the appraisal of health system performance
in Singapore.
Evaluation and development of dengue antigen detection methods.
Faculty of Medicine Research Report 2003
125
PRESS CLIPPINGS
4
1
Doctors, scientists unite against virus
28 Apr 2003
4
Docs grew eye ‘patch’- from her own eye
20 Jan 2003
2
Big increase in breast cancer
27 Feb 2003
5
Detecting Down’s syndrome without risking unborn baby
18 Jan 2003
3
Local drug set to enter world market
14 Nov 2003
6
Look, hope for poor sight is at hand
11 Feb 2003
1
5
2
3
6
10 Medical Drive Singapore 117597
Telephone: 6874 3297, 6874 3298 Fascimile: 6778 5743
http://www.med.nus.edu.sg/research/file/rschrpt2003/NUSMed.pdf