New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Anand, Mona
TFF Clinical Research Fellowship Cross Cancer Institute (Alberta Cancer Board), Edmonton , Canada
Biomedical
Role of SHP1 in ALK-expressing anaplastic large cell lymphoma
47,500
Aviv, Tzvi
TFF Research Fellowship - Biomedical 42,813
Hospital for Sick Children, Toronto, Canada
Investigating the roles of the RNA-binding Musashi proteins in the self-renewal of
neural stem cells
Azad, Meghan
TFF Research Studentship - Biomedical
University of Manitoba, Winnipeg , Canada
(Declined)
Characterization of hypoxia-induced autophagy in cancer cells and the role of BNIP3
Baldwin, R. Mitchell
TFF Research Studentship - Biomedical 22,500
Ottawa Health Research Institute, Ottawa, Canada
The role of atypical protein kinase C in the chemoresistance of glioblastoma cells
Bordeleau, Marie-Eve
TFF Research Fellowship - Biomedical 41,042
Inst. de rech. en imm/cancer (IRIC), Montreal, Canada
Characterization of Meis1-containing complex in normal and leukemia stem cells
Brown, Kristy
TFF Research Fellowship - Biomedical 38,863
Prince Henry's Institute of Medical Research, Victoria, Australia
Sex, fat and breast cancer
Dr Kristy Brown obtained her PhD at the University of Montreal. She is now conducting her
postdoctoral research training in molecular regulation of estrogen biosynthesis under the
supervision of Dr Evan Simpson at the Prince Henry's Institute in Australia.
Project summary: The term 'global obesity pandemic' has become an almost fashionable buzzword, but the fact remains that hundreds of millions of people worldwide are substantially
overweight, increasing the risk of a number of life-threatening clinical conditions, including
breast cancer. Even moderate obesity doubles the risk of breast cancer. This risk increases
further with aging due primarily to an increased capacity of fat tissue to synthesize estrogens as
a function of age. The mechanism of this increase is unknown and is the focus of the current
proposal.
Previous research: For a number of years, Dr Brown has studied the regulation of the female
sex hormone estrogen, responsible for stimulating breast cancer formation in postmenopausal
women. Recently her attention has focused on a certain cell-signalling pathway which
determines how calories are utilized in the body, and in particular whether fat should be
oxidized rather than stored in the fat. Recent evidence from her laboratory suggests that this
cell-signalling pathway is also involved in blocking estrogen formation in the breast. Thus she
proposes that obesity and aging both increase the risk of breast cancer because in obese and
elderly individuals the pathway is blocked. As a consequence, estrogen formation in the breast
is increased and the risk of breast cancer is increased also.
Project description: The cellular and molecular mechanisms underlying the increased risk of
breast cancer associated with obesity and aging are not well understood. The goal of the
project is to provide a detailed explanation at the cellular and molecular level of these
correlations. This would in turn suggest targets for therapeutic intervention and perhaps also for
a routine screening procedure to assess breast cancer risk.
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Impact and relevance: Dr Brown believes that this study may well reveal new targets for
therapeutic intervention, and may also allow for the development of a straightforward test to
assess breast cancer risk in individuals who are obese and/or elderly. For these reasons, the
successful completion of this project is in accordance with NCIC's mission to undertake and
support cancer research and related programs in Canada that will lead to the reduction of the
incidence, morbidity and mortality from cancer.
Category of Research: Fundamental research
Cancer Site Relevance: Alimentary tract & various cancer sites
Cairns, Robert
TFF Research Fellowship - Biomedical 43,353
Ontario Cancer Institute/PMH, Toronto, Canada
Genetic and epigenetic control of oxygen consumption in solid tumors: altering tumor physiology for
therapeutic gain
Cheang, Maggie Chon U
TFF Research Fellowship - Biomedical 40,000
University of North Carolina, Chapel Hill, USA
Biological classification of breast tumors to predict selective benefits for different
neoadjuvant chemotherapy regimens
Dr Maggie Cheang obtained her PhD at the University of British Columbia. She is now
conducting her postdoctoral research training in breast cancer genetics under the supervision of
Dr Charles Perou at the University of North Carolina at Chapel Hill.
Project summary: New techniques like gene expression profiling have shown that human breast
cancers are actually several distinct diseases. There is a pressing need for improved therapy
options for aggressive breast tumours. There is also the question of whether patients with a
good prognosis need aggressive treatments. The ultimate goal of Dr Cheang's research is to
identify the best therapies for patients. She will identify and distill the hundreds of potentially
significant genes defining key molecular subtypes of breast cancer based on their clinical
importance.
Previous research: New techniques like gene expression profiling have shown that human
breast cancers are actually several distinct diseases.
Project description: Dr Cheang will identify and distill the hundreds of potentially significant
genes defining key molecular subtypes of breast cancer based on their clinical importance.
Impact and relevance: This information may help to design clinical trials for cancer patients that
are based on tailored therapies, and could result in reduced toxicity and improved patient
outcomes.
Category of Research: Intervention research
Cancer Site Relevance: Breast
Corson, Timothy
TFF Research Fellowship - Biomedical
Yale University, New Haven, USA
(Declined)
Conformation-specific degradation of activated Ras
Cruz-Munoz, Mario
TFF Research Fellowship - Biomedical 45,104
IRCM - Clinical Research Institute of Montreal, Montreal , Canada
CRACC, a novel regulator of immune cell-mediated cytotoxicity
Delisle, Jean-Sebastien
TFF Clinical Research Fellowship - Biomedical
University of Montreal, Montreal, Canada
(Declined)
Regulation of major histocompatibility complex (MHC) molecules expression on normal and neoplastic cells
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Demers, Melanie
TFF Research Fellowship - Biomedical 40,469
Harvard University, Boston, USA
Role of adhesion molecules-mediated platelets interaction on the behaviour of tumor cells and angiogenesis
in vivo
Dikeakos, Jimmy Dimitrio
TFF Research Fellowship - Biomedical
University of Oregon, USA
(Declined)
The role of PACS-2 in regulating apoptosis and colorectal cancer
Dion, Vincent
TFF Research Fellowship - Biomedical 40,521
Friedrich Miescher Institute (Switzerland), Basel , Switzerland
The mechanism of homology search during homologous recombination
Dr Vincent Dion is a Canadian who obtained his PhD at the Baylor College of Medicine. He is
now conducting his postdoctoral research training in functional genomics under the supervision
of Dr Susan Gasser at the Friedrich Meischer Institute in Basel, Switzerland.
Project summary: DNA often breaks and then needs to be repaired. In order to repair itself, the
broken piece of DNA needs to move around the nucleus in search of an identical template that
can be used for accurate repair. Failure to correctly repair DNA causes mutations such as
translocations, the most common cause of leukemia (blood cancer). I want to understand how
broken DNA is accurately repaired, and why sometimes mutations arise and cause cancer.
Previous research: In the lab, Dr Dion can break DNA and watch how long it takes to repair
itself and how it happens. This can be done with a combination of genetics and state-of-the-art
microscopy techniques.
Project description: This research aims to answer the following questions: Does movement of
the broken DNA have an impact on accurate repair? What about the position of the break within
the cell? Does DNA organization (density, packaging, etc) have an effect on finding the
appropriate template for repair? Dr Dion aims to find out what aspects of DNA dynamics are
important in repairing breaks and in sometimes generating cancer-causing translocations.
Impact and relevance: Cancer is often caused by the accumulation of mutations in the DNA.
These mutations arise because the cell's repair machinery makes mistakes or stops doing its
job properly. This is exactly what happens in many types of leukemia (blood cancers). Thus,
studying the mechanism of translocation will shed light on cancer formation. In addition,
chemotherapy and radiotherapy often cause translocations and, consequently, patients develop
leukemia a few years after their initial treatment for an unrelated cancer. Therefore,
understanding how and why translocations occur will help in designing therapeutic approaches
that will prevent secondary cancers.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Dixon, Scott
TFF Research Fellowship - Biomedical 6,910
University of Toronto, Toronto, Canada
Identifying and exploiting conserved lethal genetic interactions between DNA damage response genes to
selectively kill tumor cells
Dr Scott Dixon obtained his PhD at the University of Toronto. He is now conducting his
postdoctoral research training in molecular oncology / tumor immunology under the supervision
of Drs Charles Boone and Daniel Durocher at the University of Toronto.
Project summary: The genetic material (DNA) of cancer cells is usually mutated in various
places. It may be possible to take advantage of these differences in the DNA between
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
cancerous and normal cells to develop new, highly-selective anti-cancer drugs with few side
effects. I will use a simple model cell, yeast, and human bone-cancer cells to try and find such
drugs.
Previous research: Previous studies have identified a small number of DNA mutations that allow
cancer cells to be killed by drugs that are not toxic to surrounding cells. As each type of cancer
is unique, a more systematic search of mutations and drugs will be required if we are to identify
the best possible combination in each case. Automated tools developed in recent years now
allow for thousands of mutation-drug combinations to be examined simultaneously, increasing
the chances of finding drugs that kill cancerous but not normal cells.
Project description: Dr Dixon will start with yeast cells which have DNA mutations similar to
those seen in human cancer cells. He will then add a second mutation in a second location of
the yeast DNA to determine whether the addition of this second-site mutation can kill the yeast
cells. The advantage of using yeast for these experiments is that large numbers of DNA
mutations can be examined quickly and cheaply. If a second-site mutation is effective at killing
yeast cells, he will then test whether or not this mutation can be used to selectively kill human
cancer cells. If it can, he will search for drugs that can mimic the effects of this second-site
mutation by preventing that portion of DNA from working properly, and see if this treatment is
able to selectively kill human cancer cells.
Impact and relevance: Traditional cancer treatments such as radiation or chemotherapy are not
selective; they kill cancer cells but also affect normal cells leading to undesirable side effects.
The approach described here should help identify many new combinations of treatments that
can kill cancer cells more selectively, and with fewer side effects, than existing techniques.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Dormoy-Raclet, Virginie
TFF Research Fellowship - Biomedical 43,021
McGill University, Montreal, Canada
Role of RNA-binding protein HuR in cancer induced muscle wasting
Dr Virginie Dormoy-Raclet obtained her PhD at the University Bordeaux II France. She is now
conducting her postdoctoral research training in molecular pathology under the supervision of
Dr Imed Gallouzi at McGill University.
Project summary: "Cachexia," meaning the excessive loss of body weight, is frequently seen in
patients with chronic diseases such as cancer. Rapid loss of body mass is also associated with
the rapid wasting of muscle tissue. Indeed, 20% of all cancer deaths can be attributed to
consequences arising from cachexia, such as lower quality of life and a decreased response to
chemotherapy. Dr Dormoy-Raclet is working to identify the genes involved in mediating this
detrimental consequence which arises in certain cancers.
Previous research: This laboratory is working on an RNA binding protein named HuR. Dr
Dormoy-Raclet has recently shown that HuR regulates a certain gene named iNOS, and that
this is a key step in the induction of muscle wasting.
Project description: Dr Dormoy-Raclet will use an artificial mouse muscular cell system to
identify the molecular mechanisms that mediate the loss of muscle mass. We believe that HuR
can control the formation of several key proteins which appear to cause the wasting of muscle
mass seen in cancer patients suffering from cachexia. If she can understand the pathways by
which HuR functions as an RNA binding protein, she will be able to control the expression of
numerous genes all at once rather than one at a time.
Impact and relevance: She hopes that this will allow her to identify potential anti-cachetic
compounds which will help reduce cancer induced muscle wasting and thus lower the morbidity
and mortality of this cancer-induced condition.
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Category of Research: Fundamental research
Cancer Site Relevance: Alimentary tract, lung & prostate
Douziech, Melanie
TFF Research Fellowship - Biomedical
Inst. de rech. en imm/cancer (IRIC), Montreal , Canada
(Declined)
The function of Cdc14 and condensin in chromosome segregation
Dowling, Ryan
TFF Research Studentship - Biomedical 22,500
McGill University, Montreal, Canada
Selective replication of picornaviruses in cancer cells: the role of cell-specific translational control mechanisms
Drobic, Bojan
TFF Research Studentship - Biomedical 22,500
Manitoba Institute of Cell Biology, Winnipeg, Canada
Functional characterization of histone H3 kinases, MSK1 and MSK2 in oncogene-transformed cells
Dube, Nadia
TFF Research Fellowship - Biomedical 44,063
European Molecular Biology Laboratory, Heidelberg, Germany
The role of the small GTPase Rap1 and its guanine exchange factors PDZ-GEFs in cell-cell junction formation
Emberley, Ethan
TFF Research Fellowship - Biomedical
California Institute of Technology, Pasadena, USA
(Declined)
Effect of substrate binding on the SCF-CSN-CAND1 pathway
Fabian, Marc
TFF Research Fellowship - Biomedical 47,708
McGill University, Montreal, Canada
Elucidating the mechanism behind miRNA-mediated mRNA deadenylation
Dr Marc Fabian obtained his PhD at York University. He is currently conducting his postdoctoral
research training in functional genomics focused on miRNA under the supervision of Dr Nahum
Sonenberg at McGill University.
Project summary: Within the human genome there are hundreds of small RNA molecules,
called micro-RNAs (miRNAs). Dr Fabian will use a mammalian cell-derived extract, in which
miRNAs can function, in order to better understand how miRNAs regulate other genes. T
Previous research: Recent research has demonstrated that the role of miRNAs is to regulate
the degree to which other genes are expressed, however it is still not clear how they do this.
Analysis of tumour samples has shown that the levels of miRNAs in cancerous cells can be very
different from their levels in normal tissues.
Project description: Dr Fabian will use a mammalian cell-derived extract, in which miRNAs can
function, in order to better understand how miRNAs regulate other genes. This system,
developed by Dr Sonenberg's laboratory, provides a powerful tool for studying miRNA in a test
tube instead of in a cellular environment. This will allow Dr Fabian to carry out experiments and
ask questions that would be difficult or impossible using living cells. Previously, Dr Fabian has
used this mammalian cell-derived extract to identify key characteristics of miRNAs
Impact and relevance: Understanding how miRNAs work is of critical importance in better
detecting and treating cancer, since altered patterns of miRNA expression are associated with
such cancers as chronic lymphocytic leukemia, prostate cancer, lung cancer, and breast
cancer.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Fellouse, Frederic
Mount Sinai Hospital, Toronto, Canada
Intrabodies as tools to dissect cell signaling
Grant Type
$ Awarded
2008/2009
TFF Research Fellowship - Biomedical
(Declined)
Ferraiuolo, Maria
TFF Research Fellowship - Biomedical 41,563
McGill University, Montreal, Canada
Physical interaction mapping of the Hox A cluster during normal and leukemic hematopoiesis
Dr Maria Ferraiuolo obtained her PhD at McGill University. She is now conducting her
postdoctoral research training in molecular oncology and developmental biology under the
supervision of Drs Michael Hallett and Josee Dostie at McGill University.
Project summary: If DNA within a cell nucleus is incorrectly packaged or organized it may lead
to improper gene expression (or functioning) which can lead to cancer. Dr Ferraiuolo will use a
highly innovative technology called Chromatin Conformation Capture (3C) to map the threedimensional organization of a set of genes. This will help to define the impact of genome
organization.
Previous research: A powerful new technology to measure genome-scale DNA packaging was
developed, called 5C (3C-Carbon Copy). In addition to validating known interactions with this
technology, new ones were also identified. Therefore, 5C can be used as a tool to identify
normal and aberrant gene expression.
Project description: This team will map the physical interactions within a cluster of genes called
HoxA during normal blood cell development (hematopoiesis) and in leukemia cell lines. Hox
genes are important for normal development.
Impact and relevance: Understanding the mechanisms regulating Hox gene expression is
important because improper Hox gene expression can cause cancer. Dr Ferraiuolo expects to
identify Chromatin Conformation Signatures which will serve as a new class of cancer
biomarker. These studies may lead to the development of new methods of prognosis,
treatment, and prevention of cancer.
Category of Research: Fundamental research
Cancer Site Relevance: Hematopoietic
Franovic, Aleksandra
TFF Research Studentship - Biomedical 23,125
University of Ottawa, Ottawa, Canada
Targeting the HIF-2-alpha oncogenic pathway in human cancer
Aleksandra Franovic is conducting her graduate research training under the supervision of Dr
Stephen Lee at the University of Ottawa.
Project summary: Human cancers can vary greatly but do share many physiological attributes.
For instance, the rapid growth of a tumour creates regions of low oxygen tension as the cells
distance themselves from existing blood vessels. This reduction in oxygen supply leads to the
activation of several genes that promote cancer cell survival under these conditions. Ms
Franovic is currently addressing the possibility that the reduction in oxygen levels frequently
observed in cancers acts as a trigger of tumour growth.
Previous research: Ms Franovic has been investigating the mechanisms involved in the
development of an inherited form of kidney cancer. The gene mutation that causes this kidney
cancer results in the inappropriate activation of a molecule, called HIF2a, which is normally
present only when oxygen levels are low. It subsequently induces the unregulated growth of
cells, ultimately giving rise to kidney cancer. This same molecule is also activated in most other
human cancers due to the reduced oxygen levels commonly observed in solid tumors. It is,
thus, reasonable to presume it would contribute to development of these cancers as it does in
the case of kidney cancer. In support of this notion, preliminary data suggest that inhibiting
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
HIF2a prevents brain and breast tumor formation in mice.
Project description: Ms Francovic proposes to examine the role of HIF2a in the development of
several different cancer types. She will begin her studies by determining the effect of inhibiting
HIF2a, using a common gene silencing technique, on the ability of various cancer cells to form
tumours in mice. She will then examine the effect of blocking it once the tumours have already
reached a certain size. This will verify its contribution in late-stage disease progression and its
validity as a therapeutic target in the treatment of human cancers.
Impact and relevance: While human cancers can be highly diverse at the genetic and molecular
level, the microenvironments of solid tumours display several near-universal features. It will be
very useful to better understand how common environmental stressors, such as reduced
oxygen levels, can directly affect the malignant properties of cancer cells, including their ability
to grow and metastasize. This may lead to the development of therapies to treat most human
cancers.
Category of Research: Fundamental research
Cancer Site Relevance: Brain/neurological, breast, colon/rectum & various other sites
Fraser, Michael
TFF Research Fellowship - Biomedical 37,622
Ontario Cancer Institute/PMH, Toronto, Canada
Regulation of DNA double-strand break repair and radiosensitivity in prostate cancer: possible implication of
cancer stem cells and the akt pathway
Dr Michael Fraser obtained his PhD at the University of Ottawa. He is now conducting his
postdoctoral research training in functional genomics and molecular oncology under the
supervision of Dr Robert Bristow at the Ontario Cancer Institute/Princess Margaret Hospital.
Project summary: Prostate cancer is responsible for over 4000 deaths per year in Canada. The
disease is typically treated with radiation, which causes damage to the genetic material (DNA)
within the tumour cells. DNA damage causes most cells to stop growing and ultimately die.
However, many prostate cancer cells possess an ability to repair DNA damaged by radiation,
and this often results in a failure of radiation therapy. In fact, radiation therapy fails in 25-30% of
all prostate cancer patients, leading to incurable disease. As such, a better understanding of
how prostate cancer cells repair damaged DNA will allow us to improve radiation therapy and to
develop new treatments for this disease, including new drugs that target specific components of
the DNA repair system.
Previous research: Many of the major genes involved in DNA repair have been identified, and
Dr Fraser will benefit from the previous development of advanced research tools to study these
genes. In addition, he has extensive previous experience with a gene called Akt which, when
turned on in prostate cancers, is often associated with poor prognosis. However, relatively little
is known about how the Akt gene influences DNA repair, and about how it turns the function of
other genes on or off to increase the ability of the cancer cell to repair damaged DNA.
Project description: Dr Fraser will use prostate cancer cells to study genes that may enhance
the ability of these cells to repair DNA damaged by radiation. Specifically, he will investigate if
and how certain genes, including the Akt gene, turn on DNA repair and whether this allows
these cells to survive radiation. He will also examine whether these genes turn on DNA repair in
all prostate cancer cells, or whether their function is activated in only a small percentage of
prostate 'stem' cells, which are now thought by some to be the root cause of prostate cancer
development and of radiation therapy failure. He hopes to identify how radiation therapy can be
improved, and to develop and test targets for new therapies for this disease. Impact and
relevance: The research will extend current understanding of how DNA repair allows prostate
cancer cells to survive radiation. This may lead to an improvement in the delivery of current
therapies such as radiation, and may point to new therapies that will reduce the significant
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
mortality rates associated with this disease
Category of Research: Fundamental research
Cancer Site Relevance: Prostate
Furic, Luc
TFF Research Fellowship - Biomedical 41,563
McGill University, Montreal, Canada
Study the role of elF4E and its phosphorylation at Ser-209 in tumour development and progression
Dr Luc Furic obtained his PhD at the University of Montreal. He is now conducting his
postdoctoral research training in molecular oncology under the supervision of Dr Nahum
Sonenberg at McGill University.
Project summary: Dr Furic is studying the interplay between the regulation of protein synthesis
(a process known as translation) and cancer malignancy. Extracellular signals provided by
hormones, growth factors and nutrients are relayed to the translational machinery by signalling
cascades such as the Ras/RafiErk and PI3WAKTlmTOR pathways. The initiation factors,
predominantly a subfamily of proteins called the eIF4s, are responsible to control the rate of
protein synthesis.
Previous research: Dr Furic and his colleagues have generated a mouse model in which the
eIF4E protein is mutated (eIF4E-KI) so as to be non-phosphorylatable and thus should not
respond adequately to signalling pathways involved in cellular growth. We have shown that
mouse embryonic fibroblasts (MEFs) derived from the eIF4E-KI mice are more resistant to
cellular transformation induced by oncogenes.
Project description: We will cross the eIF4E-KI mice with mice carrying deletions in known
tumour suppressor genes (PTEN and p53) with mice over-expressing oncogenes (Ras). The
resulting progeny will be monitored for tumour development and cancer progression.
Impact and relevance: Many human cancers are characterized by an over expression of eIF4E.
This study will help in understanding how deregulation of translation impacts oncogenesis, and
will dovetail with current clinical cancer treatments that target the signalling pathways regulating
translation initiation.
Category of Research: Fundamental research
Cancer Site Relevance: Breast, prostate & various other sites
Gallardo, Franck
TFF Research Studentship - Biomedical 22,500
University of Montreal, Montreal, Canada
Telomerase trafficking and maintenance of genome integrity
Franck Gallardo is conducting his graduate research training under the supervision of Dr Pascal
Chartrand at the University of Montreal.
Project summary: In order to properly grow and divide, normal cells must maintain the integrity
of their genome (genetic material). Telomeres are the caps at the ends of chromosomes and
are essential for maintaining the chromosome's stability and therefore the DNA sequence. If
telomeres shorten this leads to genomic instability and can lead to the rise of cancer. Dr
Chartrand's laboratory uses a simple yeast organism to identify and understand the
mechanisms of telomere maintenance, a process crucial for the rise of cancers in humans.
Previous research: The budding yeast has become a key model organism to study the
mechanisms of telomere maintenance, especially since these mechanisms are similar in
humans. Mr Gallardo has access to cutting-edge technology in microscopy to look inside yeast
cells and observe the enzyme called telomerase, which is responsible for the maintenance of
telomeres. He has been able to describe the trafficking of the telomerase in yeast, and identify
new pathways involved in the regulation of this enzyme.
Project description: The laboratory of Dr Chartrand is using the budding yeast as a model
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
system to further understand two processes that are crucial in the development of cancer: 1)
how cancer cells regulate their telomerase in order to maintain the telomeres at the extremities
of their chromosomes, and 2) How the telomerase is regulated in order to not interfere with the
processes of repair when the cell DNA is damaged.
Impact and relevance: Most cancer cells require telomerase to proliferate, and genetic instability
is a hallmark of cancer. Identifying the pathways involved in the regulation of telomerase and
telomeres will help to understand how tumours arise and develop into cancer, and also reveal
new potential targets for cancer therapy.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Garnett, Mathew
TFF Research Fellowship - Biomedical
University of Cambridge, Cambridge United Kingdom
(Declined)
The role of HMG20b in cytokinesis and maintenance of genomic stability
Goswami, Rashmi
TFF Clinical Research Fellowship 47,500
Ontario Cancer Institute/PMH, Toronto, Canada
Biomedical
MicroRNA expression as a prognostic marker in patients with mantle cell lymphoma
Dr Rashmi Goswami obtained her medical degree at the University of Toronto. She is now
conducting her postdoctoral research training in molecular oncology under the supervision of Dr
Suzanne Kamel-Reid at the Ontario Cancer Institute/Princess Margaret Hospital.
Project summary: Mantle cell lymphoma is a cancer of white blood cells with varying prognosis.
Currently, no good markers exist for use in determining the prognosis of a patient with mantle
cell lymphoma. MicroRNAs (miRNAs) are a special class of RNA molecules that are known to
control expression of genes (what genes do), which can cause cancer if they are expressed in
abnormal amounts. Dr Goswami will be studying miRNAs in mantle cell lymphoma samples to
determine whether abnormal expression of miRNAs can more accurately predict patient
outcome.
Previous research: MicroRNAs have been extensively studied since their discovery in the early
1990's and are abnormally expressed in cancers of white blood cells (specifically B-cell
lymphomas). An Italian group has demonstrated over-expression of a specific family of
microRNAs in a cell line developed from a woman with an aggressive form of mantle cell
lymphoma. It appears that different forms of mantle cell lymphoma may have different
expression patterns and further study is necessary to determine if this is the case.
Project description: Dr Goswami has a set of approximately 50 mantle cell lymphoma samples
of different types and with different patient outcomes. She will extract RNA from each sample
and perform quantitative real-time polymerase chain reaction. She will then link a pattern of
microRNA expression to patient outcome. To make sure that her observation is real, she will
examine expression of proteins known to be controlled by the abnormally expressed miRNAs in
a separate set of mantle cell lymphoma samples. With these data, she expects to discover a
pattern of miRNA expression that will predict patient outcome as well as genes that may cause
more aggressive forms of mantle cell lymphoma.
Impact and relevance: Mantle cell lymphoma has a varied prognosis. This is important because
currently patients with mantle cell lymphoma all receive the same therapy even though some
would be cured with less toxic treatment while others would need stronger chemotherapy to
improve. If a set of markers can help subdivide patients into different risk groups, She expects
that her research will lead to better patient mortality and morbidity.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Goulet, Brigitte
TFF Research Fellowship - Biomedical 43,125
London Regional Cancer Centre (CCO), London, Canada
Global analysis of nuclear maspin, a tumour suppressor gene in breast cancer metastasis
Dr Brigitte Goulet obtained her PhD at McGill University. She is now conducting her
postdoctoral research in the molecular genetics of breast cancer under the supervision of Dr
Ann Chambers at the University of Western Ontario.
Project summary: Breast cancer is the most common cancer for women. It can spread to other
parts of the body, even after an operation. This research will study a protein called Maspin and
how it might be able to prevent the spread of breast cancer.
Previous research: Maspin is a "tumour suppressor", which means it can slow the growth of
normal and cancerous cells. If it is not functioning or is absent, cells can multiply out of control.
Research has shown that Maspin is diminished in some breast cancer cells, and undetectable
in metastases (cancer that has spread). Researchers have found that Maspin can affect various
critical steps in the spread of cancer. It can prevent important processes like cell movement,
invasion in other tissues and the creation of new blood vessels. The mechanisms by which
Maspin does this are not well understood.
Project description: The first part of this project will be to add Maspin back into a laboratory
breast cancer cell. The ability of the cells to invade will then be tested to see if Maspin can
make a difference. Initial tests will be done in a laboratory dish, then in mammary glands of
laboratory mice. In the second part of the project, the different molecules that help Maspin
control the behavior of a cell will be identified. A tag can be attached to Maspin and then used
to retrieve Maspin and anything that sticks or binds to it. The binding partners of Maspin will be
sorted depending on their weight and identified using a specialized machine that can recognize
different proteins by their characteristics. Finally, Dr Goulet will identify the genes that are
controlled by Maspin. The genes regulated by Maspin will be isolated and a computer program
will tell us which ones- from the tens of thousands that she has-are the ones.
Impact and relevance: In the end stages, breast cancers will metastasize and lead to death.
There is almost no cure at this point since there are no operations and chemotherapy is not
strong enough. Any treatment also has side effects which can be unpleasant and intolerable.
Understanding how a molecule like Maspin can prevent the spreading of cancer to other sites in
the body is therefore a crucial step in finding more targeted treatment. For example, specific
drugs aimed at restoring Maspin could be designed to kill or turn cancer cells into dormant cells.
Using such drugs may be an alternative to radiation or chemotherapy and could improve the
quality of life of people being treated for breast cancer.
Category of Research: Fundamental research
Cancer Site Relevance: Breast
Goulet, Isabelle
TFF Research Studentship - Biomedical
University of Ottawa, Ottawa, Canada
(Declined)
The role of arginine methylation in breast cancer
Griffith, Malachi
TFF Research Studentship - Biomedical 18,750
BC Cancer Agency (Vancouver), Vancouver, Canada
The use of novel genomic approaches to identify and characterize genes associated with 5-FU resistance in
colorectal cancer
Malachi Griffith is conducting his graduate research training under the supervision of Dr Marco
Marra at the BC Cancer Agency.
Project summary: Cancer is often treated by a combination of surgery, radiation and
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
chemotherapy. Unfortunately, some patients' cancers are resistant to chemotherapy due to
differences in their genes. I am studying a drug called 5-fluorouracil (5-FU) which is commonly
used to treat colorectal, breast and other cancers following surgery. The ability of 5-FU to kill
tumour cells is thought to be influenced by many genes that vary from person to person. Mr
Griffith hopes to identify the precise variations in these genes that cause some patients to
respond favourably to treatment, while others do not.
Previous research: In recent years, a few of the genes that specifically influence 5-FU action in
colorectal cancer have been identified. Mr Griffith recently identified a novel variant of an
additional gene that may cause resistance to 5-FU in some patients. Although knowing the
identity of these genes is a good start, it only explains the response to 5-FU in some patients.
Access to cutting edge genomic tools will allow him to detect many more gene variants and
predict 5-FU response in a larger percentage of patients.
Project description: Mr Griffith is identifying gene variations that cause drug resistance using
colorectal cancer cells and patient samples that are resistant to 5-FU. Since the human genome
has many thousands of genes, searching for those small variations can be as hard as finding a
needle in a haystack. However, he will use two new scientific tools to advance study of these
genes. The first tool measures the amount and assembly of each gene present (some genes
can be put together in several ways). The second identifies small sequence variations in each
gene. Since both of these tools can be used to simultaneously examine the majority of human
genes, this is like using a large magnet to find the needle in the haystack very quickly and
efficiently. The list of candidates that emerges will be valuable in developing simple tests to
predict the response to 5-FU for any cancer patient that enters the clinic.
Impact and relevance: Currently 5-FU is given to most colorectal cancer patients, often as a
part of a drug cocktail. Although this drug is very effective in some patients, many do not benefit
from the treatment and needlessly suffer from the side effects. If we can understand what
causes resistance to 5-FU, we can use this information to avoid giving the drug to patients who
are unlikely to benefit. Furthermore, if he can understand what causes resistance to drugs, he
can use this information to design new drugs to combat or avoid this resistance. This study
represents one contribution to the ultimate goal of one day tailoring cancer treatments to the
needs of individual patients and lessening the incidence, morbidity and mortality from cancer.
Category of Research: Fundamental research
Cancer Site Relevance: Colon/rectum & various other sites
Hansotia, Tanya
TFF Research Fellowship - Biomedical
Mount Sinai Hospital, Toronto, Canada
(Declined)
Elucidating the role of serum and glucocorticoid regulated kinase-3 (SGK3) in mammary tumorigenesis
Haynes, Jennifer
TFF Research Fellowship - Biomedical 42,604
University of California (San Francisco), San Francisco, USA
Regulation of arp2 phosphorylation in metastatic carcinomas and epithelial-mesenchymal transition
Dr Jennifer Haynes obtained her PhD at the University of Toronto. She is now conducting her
postdoctoral research training in molecular biology under the supervision of Dr Diane Barber at
the University of California, San Francisco.
Project summary: The "skeleton" of the cell, called the cytoskeleton, provides structural support
for the shape of the cell and mechanical force for cell movement. During the development of
cancer, rearrangement of the cytoskeleton is necessary for tumour cell metastasis, the spread
of cancer cells from the primary site of disease to another area of the body. Dr Haynes will use
yeast as a model organism to study how signals causing cytoskeleton rearrangement control
cell motility during progression of cancer in humans.
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Previous research: Work from the host supervisor's lab discovered a previously unknown
mechanism for how a master regulator of cytoskeleton rearrangement controls cell movement.
Because this master regulator is found in most organisms from human to yeast, and yeast is a
very well-characterized model organism, Dr Haynes will use yeast cells to identify other signals
that control cytoskeleton through this mechanism. Previously, she combined biochemical, cell
biological and genetic approaches using yeast cells to study how other proteins found in
humans and yeast control cytoskeleton rearrangement.
Project description: The goal of Dr Haynes's research is to understand how the cytoskeleton
controls cell motility during cancer cell metastasis. Her approach involves identifying and
characterizing regulators controlling cytoskeleton rearrangement. The experimental design
incorporates the powerful genetics and experimental accessibility of yeast to identify
evolutionarily conserved cytoskeleton regulators in yeast and mammals. Additionally, she will
perform complementary studies using human cancer cells to determine the regulation and
function of key cytoskeleton regulators in metastatic carcinomas. Elucidating the molecular
basis of cytoskeleton dynamics will ultimately advance our understanding of factors contributing
to cancer as well as its treatment.
Impact and relevance: The high degree of conservation of cytoskeleton regulators among all
cells, including yeast and human cells makes yeast an excellent system for studying the
cytoskeleton. Much of our knowledge of cytoskeleton function gained from experiments
conducted in yeast has been directly applied to mammalian systems. Understanding how the
cytoskeleton controls cell motility in humans is important because increased cell motility is
necessary for tumour cell metastasis and the spread of cancer cells within the body.
Importantly, because metastatic carcinomas and not solid epithelial tumours are the primary
cause of cancer-related mortality, factors controlling metastasis are important targets for
therapeutics to restrict cancer progression. A better understanding of how cytoskeleton
dynamics are regulated will lead to the identification of new markers of cancer progression and
potential targets for cancer therapy. I expect studies of cytoskeleton regulation to provide the
conceptual framework from which practical approaches for cancer treatment will be developed.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Heinonen, Krista
TFF Research Fellowship - Biomedical 42,501
Inst. de rech. en imm/cancer (IRIC), Montreal, Canada
Wnt signaling and T cell development: is Wnt sufficient to make a thymus?
Hope, Kristin
TFF Research Fellowship - Biomedical
Inst. de rech. en imm/cancer (IRIC), Montreal , Canada
(Declined)
Dissecting hematopoietic stem cell self-renewal with RNA interference
Hudon, Valerie
TFF Research Studentship - Biomedical 22,500
McGill University, Montreal, Canada
Investigating the functions of FLCN, a novel gene involved in kidney tumor formation
Hyenne, Vincent
TFF Research Fellowship - Biomedical 43,125
Inst. de rech. en imm/cancer (IRIC), Montreal, Canada
Defining the role of the Brat family of tumor suppressors in C. elegans embryonic polarity
Ishiyama, Noboru
TFF Research Fellowship - Biomedical
Ontario Cancer Institute/PMH, Toronto, Canada
(Declined)
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Structure and function of cadherins and catenins in cell-cell adhesion
Johnson, Nathalie
TFF Clinical Research Fellowship 47,500
BC Cancer Agency (Vancouver), Vancouver, Canada
Biomedical
Development of a novel prognostic model in follicular lymphoma
Dr Nathalie Johnson obtained her PhD at the University of British Columbia. She is now
conducting her postdoctoral research training in molecular oncology under the supervision of Dr
Randy Gascoyne at the BC Cancer Agency.
Project summary: Follicular Lymphoma (FL) is a very common form of lymphoid cancer and is
incurable. The spectrum of clinical outcome varies from occasional spontaneous remissions to
aggressive forms of FL with survivals measured only in months. The immune response to the
tumour and alterations in critical genes within the tumour appear to predict overall survival in
small studies but this needs validation. Dr Johnson and her colleagues plan to identify the most
significant factors that predict overall survival and incorporate these into a clinically useful
model.
Previous research: The FL International Prognostic Index (FLIPI) uses clinical variables to
predict tumour behavior. However, this clinical tool is imprecise and does not represent the
underlying tumour biology. Using gene microarray technology, Dr Johnson and her colleagues
have detected 85 genes that are highly predictive of survival in FL. They have also identified
novel genetic changes in FL malignant cells that may be important in tumour progression.
Project description: Using microarray technology, Dr Johnson plans on validating the prognostic
value of candidate genes. She will then create a new prognostic model using only validated
biological markers. She will also develop strategies to help bring this into the clinical arena by
using techniques that could be applied by most hospital laboratories.
Impact and significance: This model should lead to improved, individualized patient therapy for
follicular lymphoma. Patients identified as having low risk disease may be best managed by
deferring therapy thus sparing them from the toxicity of chemotherapy. Patients identified as
having aggressive FL at high risk of early death may be candidates for early intervention and
clinical trials. Ultimately, this project should also lead to major advances in our understanding of
FL biology and identify novel targets for therapy.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Joshi, Purna
TFF Research Studentship - Biomedical 22,500
Ontario Cancer Institute/PMH, Toronto, Canada
TIMP-mediated regulation of mammary stem cell niche
Juvet, Stephen
TFF Clinical Research Fellowship 47,500
University of Toronto, Toronto, Canada
Biomedical
Dissecting the mechanisms of CD4-CD8- alpha/beta TCR+ double negative regulatory T cell-mediated
suppression of graft-versus-host disease
Kim, Edward
TFF Research Fellowship - Biomedical 42,292
University Health Network, Toronto, Canada
The role of inflammation and the extracellular matrix protein MFAP4 for the anti-tumor activity of doublenegative T cells
Dr Edward Kim obtained his PhD at the University of British Columbia. He is now conducting his
postdoctoral research training in tumour immunology under the supervision of Dr Li Zhang at
the University Health Network.
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Project summary: In order to help eradicate tumours, our immune system contains specialized
cells that can recognize and kill tumour cells. These cells rely on cues provided by tumours and
tissues to recognize tumour cell targets, and to execute anti-tumour killing activity. Immune cells
that do not express molecules that can detect tumours are less functional. Failure of these
specialized immune cells to express genes critical for sensing such cues is dangerous, as this
may lead to evasion and progression of cancer. Dr Kim will use an animal model to identify and
understand genes that are important for our immune system's ability to detect tumour cells and
prevent the formation and progression of cancers.
Previous research: As mice have been studied and characterized extensively for the study of
anti-tumour immunity. Dr Kim will use cutting-edge tools to efficiently identify and characterize
the function of genes important for anti-tumour function. He has previously identified a novel
gene that appears to be critical for the tumour-killing ability of immune cells.
Project description: Dr Kim will use a mouse model system in which the gene he is studying will
be rendered non-functional, and a tumour model will be used to investigate how the immune
cells depend on this gene to kill tumours. A better understanding of how the immune system
fights tumours can lead to improved treatment of cancers.
Impact and significance: Current therapies for blood cancers such as leukemia and lymphoma
are limited by side-effects and do not always provide a cure. Our immune system has the ability
to kill tumours, but the genes that regulate their activity are not completely understood. By
identifying such genes, the processes by which our immune system fights against cancer will be
better understood. Ultimately, these genes can then be used as markers to distinguish which
immune cells would best be used for immunotherapy against cancers.
Category of Research: Fundamental research
Cancer Site Relevance: Hematopoietic, lung & various other sites
Klose, Robert
TFF Research Fellowship - Biomedical
University of North Carolina, Chapel Hill, USA
(Declined)
Understanding the link between CpG islands, histone modification, and cancer
Kolas, Nadine
TFF Research Fellowship - Biomedical 43,229
Mount Sinai Hospital, Toronto, Canada
A functional genomic screen to identify novel genes involved in the human DNAdamage response
Kongkham, Paul
TFF Clinical Research Fellowship 47,500
Hospital for Sick Children, Toronto, Canada
Biomedical
A combined epigenetic and genetic genome-wide screen identifies SPINT2 as a novel tumour suppressor
gene in medulloblastoma
Landry, Josette-Renee
TFF Research Fellowship - Biomedical 44,167
University of Montreal, Montreal, Canada
Transcriptional regulatory network of Elf-1 in normal and leukemic hematopoiesis
Larijani, Mani
TFF Research Fellowship - Biomedical 45,417
University of Toronto, Toronto, Canada
Biochemical mechanisms of activation-induced cytidine deaminase targeting
Liao, Jack
TFF Research Studentship - Biomedical 18,750
University of Toronto, Toronto, Canada
Structural and functional characterization of IFI16 interactions with tumor suppressors p53 and BRCA1
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Jack Liao is conducting his graduate research training in structural biology under the
supervision of Dr Cheryl Arrowsmith at the University of Toronto.
Project summary: Interferons (IFNs) are small signaling molecules involved in the regulation of
a variety of immunological, inflammatory and infectious diseases. IFNs have also been used as
a therapeutic agent to treat many cancers. Although the mechanism of the IFN-induced antitumour response remains poorly understood, it is believed that certain related proteins may be
critical for tumour suppression. Mr Liao will study a protein called IF116, which may play an
important role in tumour suppression. However, the molecular mechanism by which IF116
exerts its activity is still elusive... P53 and BRCAl are two well known tumour suppressors that
have been identified to interact with IFI16. Mr Liao will use structural and functional tools to
determine the three-dimensional structure of IF116 to better characterize IFI16's role in p53 and
BRCAl regulated tumour suppression.
Previous research: Several studies have shown that IF116 binds to p53 and BRCAl but a
detailed description of how IF116 modulates p53 and BRCAl function is lacking. In the
preliminary studies of IFI16lp53 interaction, Mr Liao has narrowed down the p53 interacting site
of IF116 to the conserved HIN-A domain. He has also determined the crystal structures of the
HIN-A and HIN-B domains of IFI16
Project description: Mr Liao proposes to use structural and functional studies on two aspects of
IF116 to gain more insights into IFI16's mechanistic role in the regulation of p53 and BRCA1.
First, he will determine the structures of the HIN-A and PYRIN domains of IF116 in complex
with p53 and BRCAl, respectively, to better understand IFI16-mediated p53 and BRCAl
interactions. Second, Mr Liao plans to study the effect of post-translational modifications on
IFI16's interactions with p53 and BRCAl to clarify how protein-protein interactions may be
regulated by these modifications.
Impact and significance: Overall, Mr Liao expects that the results obtained from this research
will not only enhance understanding of how IF116 may participate in the coordination of p53
and BRCAl regulated tumour suppression, but may also provide important clues as to how loss
of IF116 can give rise to cancers of the pancreas, prostate and breast, and can form the basis
for the search and development of new cancer treatments.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Lisi, Veronique
TFF Research Studentship - Biomedical
University of Montreal, Montreal, Canada
(Declined)
Understanding the role of micro-RNA in oncogenic circuits
Liu, Che-Yuan
TFF Research Fellowship - Biomedical
University Health Network, Toronto, Canada
(Declined)
Tumor initiating cells in mouse models of aggressive subtypes of breast cancer
Mallette, Frederick
TFF Research Fellowship - Biomedical 41,250
Jewish General Hospital, Montreal, Canada
The role of protein demethylases in the DNA damage response
Dr Frederick Mallette obtained his PhD at the University of Montreal. He is currently conducting
his postdoctoral research training in molecular oncology under the supervision of Dr Stephane
Richard at the Lady Davis Institute for Medical Research, Jewish General Hospital.
Project summary: DNA damage may be caused by environmental factors or normal metabolic
activity. Failure to repair DNA damage leads to mutations that may alter the function of
important genes. Mutations in such genes are the driving force behind the development of
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
tumours. However, cells possess efficient mechanisms to detect and repair DNA damage. Dr
Mallette will use cultured cells to study the DNA damage response and particularly protein
demethylases, an important family of proteins implicated in the regulation of gene expression.
Previous research: Previously, Dr Richard and colleagues demonstrated that the DNA damage
response machinery is modified by a process called arginine methylation. Furthermore, this
process plays an important role in the DNA damage response. This suggests that the reversal
of such modifications should regulate the DNA damage response and DNA repair.
Project description: Dr Mallette will investigate the role of protein demethylases in the DNA
damage response and cancer prevention. Using different biochemical markers, he will explore
how a certain group of demethylases regulates the recognition and repair of DNA breaks. The
objective of the proposed study is to bring a better understanding of the mechanisms leading to
tumour formation in humans.
Impact and significance: This research will lead to a better understanding of the molecular
mechanisms implicated in the detection and repair of DNA damage. Understanding the DNA
damage response may lead to the creation of new anti-cancer drugs and development of new
diagnosis tools to prevent cancer formation and progression.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Martin, Peter
TFF Clinical Research Fellowship Cornell University - Cornell Medical Center, New York, USA
Biomedical
Evaluation of the anti-CD74 antibody hLL1 in the treatment of B-cell malignancies
47,500
McLachlan, Elizabeth
TFF Research Fellowship - Biomedical 34,202
University of Manitoba, Winnipeg, Canada
Estrogen receptor beta target genes in human breast cancer
Dr Elizabeth McLachlan obtained her PhD at the University of Western Ontario. She is now
conducting her postdoctoral research training in molecular oncology under the supervision of Dr
Leigh Murphy at the University of Manitoba.
Project summary: The growth of breast cancer cells is controlled in part by estrogen through its
binding to estrogen receptors (ER). ER status is used as a prognostic and treatment response
indicator, and ER can be inactivated therapeutically to prevent or slow the growth of tumour
cells. Currently, all testing and treatments target ERa but more recently a second ER, ERß, has
been discovered. Dr McLachlan aims to identify ERß target genes in breast cancer cells with
the goal of exploiting ERß for prognosis and/or therapeutics.
Previous research: This lab and others have shown that each ER responds differently to
estrogen and antiestrogen. The lab has established experimental cell lines that represent the
two types of human breast cancer that express ERß, those that express ERß alone and those
that also express Era.
Project description: It is this project's hypothesis that ERß targets specific genes and molecular
pathways in breast cancer cells that may be different than those targeted by ERa. In this study
state-of-the-art technologies will be used to identify and characterize specific ERß target genes
in both breast cancer cells that are ERa positive and those that are ERa negative. The
significance of the findings will be determined by screening breast tissue biopsies stored and
annotated in the Manitoba Breast Tumour Bank.
Impact and significance: Identification of two ERs, ERa and ERß, requires us to rethink how
estrogen works in breast cancer. Determination of the molecular mechanism by which ERß
regulates target genes will allow us to identify ways to modify its activity, and may provide new
therapies for breast cancer.
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Milyavsky, Michael
TFF Research Fellowship - Biomedical
University Health Network, Toronto, Canada
(Declined)
A genome scale RNAi screen for genes that control the developmental program of hematopoietic stem cells
Mittag, Tanja
TFF Research Fellowship - Biomedical 14,410
Hospital for Sick Children, Toronto, Canada
Switch-like interaction of polyvalent disordered Sic1 with the single binding site of Cdc4
Munoz Risueno, Ruth
TFF Research Fellowship - Biomedical 42,188
McMaster University, Hamilton, Canada
Identification of the microRNA profile that regulates initiation of human stem cell transformation
Dr Ruth Muñoz Risueno obtained her PhD at the Autonoma University of Madrid. She is now
conducting her postdoctoral training in cancer stem cell research under the supervision of Dr
Mick Bhatia at McMaster University.
Project summary: A growing body of evidence indicates that microRNAs (miRNAs) play
important roles in the development of human diseases such as cancer. Normal stem cells and
cancer stem cells share many cellular features; however, the mechanisms responsible for
human cancer initiation are unknown. Although, leukemia stem cells (LSCs) are a well-defined
population of cancer stem cells and their normal counterpart are blood stem cells (HSCs), their
microRNA pattern has not been defined.
Previous research: Preliminary results suggest that there are differences between LSC and.
HSC microRNA patterns. Dr Munoz Risueno found that miR-21 was overexpressed in leukemia
stem cell compared to HSCs. This microRNA has been implicated in the formation of tumours.
Project description: This project aims to understand cancer initiation by identifying events that
differentiate cancer stem cells from normal stem cells. Using LSCs as a model of cancer stem
cells, the lab will determine the microRNA pattern.These studies will enable them to determine
which cancer-like microRNA patterns, are present in leukemic stem cells and determine tumour
forming behaviour.
Impact and significance: These studies might not only have an impact on stem cell research but
might also assist biologists seeking to understand the cancer initiation progress. The bulk of
tumour suppressors and oncogenes remain to be discovered and many of them might be noncoding genes. The proposed experiments will provide clues about pathways that are disrupted
or activated in cancer, and offer potential new targets for treatment that specifically target
cancer stem cells while maintaining normal stem cells and healthy tissue.
Category of Research: Fundamental research
Cancer Site Relevance: Hematopoietic
Nouhi, Zaynab
TFF Research Studentship - Biomedical 22,500
Lady Davis Institute, Montreal, Canada
The role of CNC transcription factors in carcinogenesis
Pelletier, Benoit
TFF Research Fellowship - Biomedical 41,771
Inst. de rech. en imm/cancer (IRIC), Montreal, Canada
Regulation of p21Cip1 degradation by N-terminal ubiquitination
Peschard, Pascal
TFF Research Fellowship - Biomedical 35,765
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
University of London (UK), London, UK
Genetic analysis of the ral signalling pathways and their role in ras-mediated carcinogenesis
Dr Pascal Peschard obtained his PhD at McGill University. He is now conducting his
postdoctoral research training in molecular oncology under the supervision of Dr Christopher
Marshall at the Institute for Cancer Research in the United Kingdom.
Project summary: Normal functioning of the body requires that all cells accomplish their function
according to a precise and detailed plan. The alteration of normal growth signals may promote
the development and progression of cancer. Dr Peschard will develop mouse models to study
the role of a family of genes, Ral GTPases, in mammalian development and tumour formation.
Previous research: Intense research in the last 20 years has uncovered a number of cellular
components, the products of proto-oncogenes and tumour suppressor genes, which regulate
cell behaviour. Cancer results from alterations in the nature or the amount of proto-oncogenes
and from inactivation of tumour suppressor genes. Work in the past few years has uncovered
that Ral proteins, which are activated downstream of the well-established tumour promoting
genes Ras, may be important regulators of tumour formation.
Project description: The objective of this proposal is to precisely define the role of Ral proteins
in tumour formation. This will be achieved by developing mouse models that are lacking Ral
genes. The requirement for the Ral genes in embryonic development and homeostasis will first
be examined as it is very informative to understand the functions of Ral genes under normal
circumstances. Then, study will look into the ability of tumours and
Impact and relevance: Mice provide an excellent model to study the development and
progression of cancers because they recapitulate well the human diseases and it is possible to
manipulate their genome to add, modify or remove genes. Since Ras genes are mutated in 1520% of all human cancers, it is critical to get a better understanding of the proteins activated by
Ras, including Ral proteins. Understanding the functions of Ral proteins will allow the
development of therapeutic strategies to target them, hence switching off signals generated by
activated Ras proteins that promote growth and invasion in many human tumours. Despite the
predominant role of Ras proteins in human tumours, efficient therapeutic strategies to target
them have yet to be discovered.
Category of Research: Fundamental research
Cancer Site Relevance: Breast, lung, pancreas & skin/integument
Peschard, Pascal
TFF Research Fellowship - Biomedical
Cancer Research UK, London, UK
(Declined)
Genetic analysis of the Ral signalling pathways and their role in ras-mediated carcinogenesis
Pontier, Stephanie
TFF Research Fellowship - Biomedical 43,125
McGill University Health Centre (MUHC), Montreal, Canada
Understanding the molecular events allowing tumor cells escape dormancy
Rajakulendran, Thanashan
TFF Research Studentship - Biomedical 22,500
University of Toronto, Toronto, Canada
Mechanistic basis for regulation of the RAF kinases
Thanashan Rajakulendran is conducting his graduate research training in structural biology
under the supervision of Dr Frank Sicheri at the University of Toronto.
Project summary: The survival of healthy cells depends on a fine balance between growth and
death signals. In cancer, this balance is tipped in favour of growth signals. Mr Rajakulendran will
use an approach called structural biology to understand how cells balance growth and death
signals, and how its imbalance can cause cancer.
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Previous research: Structural biology approaches have revealed much about the inner workings
of a living cell. Previously, Mr Rajakulendran used this approach to identify a molecular complex
that is essential for cells to perceive growth signals.
Project description: Mr Rajakulendran is using structural biology approaches to study an
important aspect of cancer progression: how growth signals are turned 'on' and 'off' in cells. He
recently identified a molecular complex that is capable of acting as a switch in turning 'on' and
'off' such growth signals. He will further characterize how this switch functions, which will give
clues into how cancer cells keep this switch turned 'on' at all times.
Impact and significance: Mr Rajakulendran is using structural biology approaches to understand
how this switch for sensing growth signals operates in order to provide a close-up look into the
inner workings of a cell. Obtaining such a detailed understanding of cellular events will allow Mr
Rajakulendran to rationalize how things can go wrong in diseases like cancer. A close-up
understanding of the cell's growth-sensing switch will allow the development of new ways to
keep this switch 'off' in cancer cells, which could prove to be a very powerful means of
preventing cancer progression.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Richardson, Douglas
TFF Research Studentship - Biomedical 22,500
Queen's University, Kingston, Canada
RET internalization and sub-cellular localization: possible effects on downstream signaling and gene
expression
Roberts, Tania
TFF Research Studentship - Biomedical 3,751
University of Toronto, Toronto, Canada
Defining the role of the BRCT domain protein Rtt107 in the DNA damage response
Rosonina, Emanuel
TFF Research Fellowship - Biomedical 41,537
Columbia University, New York, USA
Regulation of RNA polymerase II transcription by Sub1/PC4 and sumoylation
Dr Emanuel Rosonina obtained his PhD at the University of Toronto. He is now conducting his
postdoctoral research training in molecular genetics under the supervision of Dr James Manley
at Columbia University.
Project summary: The basic machinery that makes a cell work is the same whether the cell
comes from a human brain, the liver of a lab rat, or even a simple yeast cell. It is often failure of
this basic machinery that leads to, or contributes to cancer progression. Dr Rosonina's specific
interest is transcription, the process by which the cell reads the information that is encoded in its
DNA, thereby giving it instructions on how to grow. In rare occasions, this system fails, causing
genes on DNA to be read at inappropriate times and places, often with detrimental
repercussions, like cancer. Dr Rosonina is studying transcription to learn the methods the cell
employs to ensure that genes are read only as appropriate.
Previous research: Many years of research have found that the process of reading information
from DNA, transcription, is a complicated, yet extremely organized event. Transcription requires
many different proteins, each with a different function. Some of these proteins are required for
transcription of specific genes, while others are required for transcription in general. It has been
found that in cancers, some of these proteins do not function as they are intended to, causing
inappropriate transcription leading to or contributing to cancer. Dr Rosonina's work involves
studying the proteins involved in transcription. In his research, he studied the role of one of
these proteins, which he found was involved in general transcription. A second aspect of his
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
work focuses on studying how the cell can change the function of proteins through
modifications. His work has uncovered how one type of these modifications can affect
transcription.
Project description: Dr Rosonina is working primarily with yeast to study two ways in which the
cell ensures transcription is appropriate. The first involves a protein called Subl in yeast and
PC4 in human cells. His work aims to identify the specific role of this protein in transcription. He
has generated yeast that are missing the Subl protein, and by studying the defects in these
yeast, he can determine how Subl functions normally. By learning what Subl does in yeast, he
can test whether PC4 plays the same role in human cells. In the second area of his research he
will determine how one type of protein modification affects transcription. To accomplish this, he
has generated cells that cannot make this modification. Testing how these cells grow and their
ability or inability to perform transcription will help in understanding what this modification does
in normal cells.
Impact and significance: The basic mechanism of transcription is common to all cells, including
yeast and human cells. Studying transcription in yeast will allow understanding of how
transcription works in healthy human cells, and how defects in transcription contribute to
cancer. The ultimate aim of this project is to contribute to the understanding of the events of
transcription, and to learn how inappropriate reading of information in genes contributes to
cancer. By learning how and why defects in transcription occur in cancer, it is possible to
understand how to correct these defects, or help avoid them altogether through screening
technologies.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Sadikovic, Bekim
TFF Research Fellowship - Biomedical 41,146
Hospital for Sick Children, Toronto, Canada
Whole-genome approach for identification of DNA methylation biomarkers of gene expression and genomic
instability in osteosarcoma
Dr Bekim Sadikovic obtained his PhD at the University of Western Ontario. He is now
conducting his postdoctoral research training in molecular oncology under the supervision of
Drs. Jeremy Squire and Maria Zielenska at the Hospital for Sick Children.
Project summary: Osteosarcoma (OS) is a bone cancer that mostly affects young people,
including Canadian icon Terry Fox. Cancer arises as a result of inappropriate gains and losses
of genes, as well as disruption in mechanisms which control how genes are turned on or off.
The combination of these effects result in altered gene dosage. This project aims to identify
these changes and provide new biological markers and therapeutic targets for 0S.
Previous research: Work from this laboratory and others have shown that OS has highly
unstable DNA resulting in gains or losses of many genes. In addition to genetic changes, a
mechanism which controls how genes are turned on or off called "DNA methylation" becomes
compromised in cancer cells. Very little is known about the mechanisms that regulate turning on
and off of genes in OS, and how such changes impact DNA stability itself.
Project description: Dr Sadikovic will use cutting edge technology to identify changes in DNA
methylation of all human genes (>25,000), and the stability of DNA in a number of OS tissue
samples and cells derived from OS patients. Specific, recurringly affected genes will then be
tested in a larger cohort of OS patient tissues to identify which of these changes are the genetic
markers of initiation and progression of OS, and to correlate such changes to regions of DNA
instability.
Impact and significance: Unlike gains and losses of genes, which result from DNA instability in
cancer, changes in DNA methylation can be reversed using specific chemotherapeutics. In
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
addition to providing genetic markers for OS, the cancer-related genes with abnormal DNA
methylation that are identified in this study will provide novel targets for cancer therapy. OS is
an important model for study of DNA instability in cancer, so better understanding of changes in
DNA methylation and DNA stability will provide new clues to the causes of cancer.
Category of Research: Fundamental research
Cancer Site Relevance: Musculoskeletal
Salsman, Jayme
TFF Research Fellowship - Biomedical 42,188
University of Toronto, Toronto, Canada
Mechanisms of disruption of promyelocytic leukaemia (PML) nuclear bodies by viral proteins
Dr Jayme Salsman obtained his PhD at Dalhousie University. He is now conducting his
postdoctoral research training in functional genomics under the supervision of Dr Lori Frappier
at the University of Toronto.
Project summary: Healthy cells have a number of molecular safeguards in place to protect
themselves from genetic damage and uncontrolled cell division. PML is one such protein that
acts as a tumour suppressor by coordinating the actions of other cellular proteins involved in
gene expression and DNA repair and antiviral responses. Some human viruses, like herpes
viruses, target and destroy PML. These viruses will be used to identify and characterize viral
proteins that target PML in order to understand more about this essential host protein and to
determine how herpes viruses, like EBV, can cause the changes that can lead to cancer.
Previous research: PML and its associated cellular components defend cells against many
types of assaults, including potentially cancer causing DNA damage and viral infections.
Although we understand the basic functions of PML, it is connected to a complicated network of
cellular processes that have not been fully characterized. Since many viruses must disable PML
pathways in order to effectively infect cells, we can learn new things about PML by observing
how viruses attack it. Dr Salsman has screened over 200 individual proteins from three different
herpes viruses for the ability to interfere with PML and has identified over 20 herpes virus
proteins that affect PML protein in a variety of different ways.
Project description: This study will promote understanding of how PML protects cells from
cancer. Dr Salsman's approach is to use standard molecular biology techniques to identify and
study viral proteins that alter the normal protective functions of PML in order to better
understand this vital cellular protein and to identify new components or functions of PML
pathways. A more complete understanding of how this multifunctional tumour suppressor
functions could identify novel targets for anti-cancer therapeutics.
Impact and significance: Many advances in cancer research have been made by studying how
viruses interfere with normal cellular processes. In order to better understand how PML, a
protein that safeguards against cancer, functions Dr Salsman will be searching for viral proteins
that interfere with its activity. These viral proteins will provide clues to the normal function of
PML and identify new ways to manipulate its activity. Knowing how to manipulate a pathway as
important as PML can be used to better understand and treat human cancers.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Sarkari, Feroz
TFF Research Studentship - Biomedical 22,500
University of Toronto, Toronto, Canada
Role of ubiquitin specific protease, USP7 in Epstein-Barr virus associated cancers
Sauvageau, Martin
University of Montreal, Montreal, Canada
TFF Research Studentship - Biomedical 22,500
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Role of the PRC2 polycomb complex in normal and leukemic stem cell self-renewal
Martin Sauvageau is conducting his graduate research training in molecular genetics under the
supervision of Dr Guy Sauvageau at the University of Montreal.
Project summary: Stem cells are uniquely defined by a process called self-renewal, whereby
cells are able to copy themselves, allowing the constant regeneration of tissues. Interestingly,
some studies suggest that self-renewal of a rare subpopulation of cancerous stem cells is
essential for sustaining leukemias and other blood cancers in patients. Therefore, to design
more efficient therapies and avoid relapses, we need a better understanding of the molecular
events implicated in the self-renewal of normal and leukemic stem cells. Mr Sauvageau will use
the mouse as a model organism to elucidate the role and regulation of candidate proteins in the
self-renewal of normal stem cells and will analyze their requirement for the maintenance of
leukemic stem cells.
Previous research: The lab in which Mr Sauvageau is conducting his research has shown that a
gene called Bmil is essential for the maintenance of both normal and leukemic stem cells. This
gene is a member of a family of 37 genes called the Polycomb Group. The products of two
other genes from this family have the ability to enzymatically modify the scaffold proteins
associated with DNA (called chromatin). Interestingly, recent studies indicate that stem cells are
characterized by a unique pattern of Polycomb-induced modifications to the chromatin.
Moreover, there are numerous reports that implicate Polycomb genes in many types of human
cancer, raising the possibility that these genes play a central role in the biology of normal and
cancer stem cell identity and in cancer development in general.
Project description: To characterize the role of these two Polycomb proteins in the self-renewal
of blood stem cells, a technique will be used to delete in vivo each gene in blood cells of
specifically engineered mice. Following deletion of the genes, the defects in the self-renewal
potential of blood stem cells will be analyzed using well established techniques for quantifying
stem cells. Leukemias will also be generated in these mice to analyze the requirement of these
two Polycomb genes for the generation and maintenance of leukemic stem cells. Cellular,
genetic and biochemical assays will be used to better characterize the function and regulation
of these genes in stem cell activity.
Impact and significance: Understanding the mechanism of stem cell self-renewal and
harnessing its potential is essential for developing treatments aimed at expanding normal stem
cell populations for life-saving procedures such as bone marrow transplants. It is also crucial for
developing new treatments targeting leukemic stem cells to eradicate blood cancers and avoid
relapses. By analyzing the role and regulation of these two Polycomb enzymes in normal and
leukemic stem cells the knowledge gained from this project will deepen our understanding of
stem cells and may uncover key targets with therapeutic potential for leukemia.
Category of Research: Fundamental research
Cancer Site Relevance: Hematopoietic
Sharom, Jeffrey
TFF Research Studentship - Biomedical 3,751
Mount Sinai Hospital, Toronto, Canada
Systematic elaboration of the signaling network emanating from the yeast Akt-like kinase Sch9
Spratlin, Jennifer
TFF Clinical Research Fellowship 12,394
University of Colorado, Denver, USA
Biomedical
A phase I study of PXD101 in combination with bortezomib (PS-341) in patients with advanced solid tumors
and lymphoma
Standish, Beau
TFF Research Studentship - Biomedical 22,500
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
University of Toronto, Toronto, Canada
Volumetric quantification of microvascular blood flow during photodynamic therapy of prostate cancer using
doppler optical coherence tomography
Sturdza, Alina
TFF Clinical Research Fellowship 43,542
University of Vienna (AT), Vienna, Austria
Biomedical
Topographic variations of the sigmoid during each application in MRI based HDR brachytherapy: In cervix
cancer patients
Dr Alina Sturdza obtained her medical degree at Carol Davila University in Bucharest, Romania.
She is now conducting her postdoctoral research training in radiation therapy under the
supervision of Dr Richard Poetter at the University of Vienna.
Project summary: The aim of Dr Sturdza's study will be to investigate and compare the
variations in sigmoid colon location during fractionated brachytherapy, a form of radiation
therapy, and its impact on treatment planning and clinical outcome.
Previous research: Image guided radiotherapy, especially MRI guided interstitial brachytherapy
(implantable radioactive `seeds') is a very new area of research, therefore there are no
published similar data on this subject. Dr Sturdza's retrospective literature review (unpublished)
showed that there is increased variability of sigmoid colon position during each radiation
delivery with MRI guided brachytherapy for cervix cancer. This could translate into a higher
dose of radiation that could be delivered safely to the cervix, with better outcome.
Project description: A prospective phase II study will be designed with the purpose of creating a
mathematical model that could predict the amount of sigmoid colon movement from fraction to
fraction and application to application during MRI guided interstitial brachytherapy. The primary
target and organ at risk will be contoured for each application in a prospective manner and a
potential correlation with the actual radiation dose delivered will be documented.
Impact and significance: This study will be important in determining the maximum safe dose of
radiation that can be delivered to the sigmoid colon. This will be very important not only in cervix
cancer patient treatment, but also in other malignancies of the pelvis, including prostate, anal
canal, rectum, and endometrial cancer.
Category of Research: Intervention research
Cancer Site Relevance: Bladder & colon/rectum
Tanguay, Pierre-Luc
TFF Research Studentship - Biomedical
Inst. de rech. en imm/cancer (IRIC), Montreal, Canada
(Declined)
Identification and characterization of the specific N-terminal E3 ubiquitin ligase of the atypical MAP kinase
Erk3
Tomic, Jelena
TFF Research Studentship - Biomedical 22,500
Sunnybrook Health Sciences Centre, Toronto, Canada
The effect of tumor suppressor p53 on interferon signalling in normal and leukemic B cells
Wang, Yemin
TFF Research Studentship - Biomedical 22,500
University of British Columbia, Vancouver, Canada
Degradation of tumor suppressor ING3 promotes cell cycle progression
Ward, Ryan
TFF Research Studentship - Biomedical
Hospital for Sick Children, Toronto, Canada
(Declined)
The cell-of-origin of chemically and genetically induced mouse brain tumours
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Warr, Matthew
McGill University, Montreal, Canada
Regulation of apoptosis by Mcl-1 turnover
Williams, Brent
University Health Network, Toronto, Canada
Immunotherapy of leukemic stem cells
Grant Type
$ Awarded
2008/2009
TFF Research Studentship - Biomedical 22,500
TFF Clinical Research Fellowship Biomedical
47,500
Wolting, Cheryl
TFF Research Studentship - Biomedical 22,500
Hospital for Sick Children, Toronto, Canada
A study of functional protein interactions in signaling and degradation
Wong, Peggy
TFF Clinical Research Fellowship 47,500
Hospital for Sick Children, Toronto, Canada
Biomedical
Deregulation of differentiation, proliferation and apoptotic pathways in T-cell leukemogenesis
Wong, Ronald
TFF Research Studentship - Biomedical 22,500
University of British Columbia, Vancouver, Canada
The role of tumor suppressor ING1b in nucleotide excision repair
Ronald Wong is conducting his graduate research training in molecular genetics under the
supervision of Dr Gang Li at the University of British Columbia.
Project summary: DNA is the genetic material in cells that codes proteins that control cellular
functions. Cells are under constant bombardment from DNA damaging agents and the damage
is repaired by various specific repair pathways. Inaccurate repair of DNA can lead to genetic
mutations that may cause cancer. Mr Wong proposes to study the action of the tumour
suppressor INGlb in repair of ultraviolet (UV) damaged DNA that is the major environment risk
factor for skin cancers, including potentially life-threatening melanoma.
Previous research: The repair machinery for UV-damaged DNA is well elucidated. However,
DNA is wrapped up in a compact structure which prevents the repair machinery from contacting
DNA. How cells regulate and overcome this structure is unknown. A tumour suppressor called
WGlb was found to be lost or altered in many cancers. Mr Wong and colleagues have
demonstrated that the tumour suppressor INGlb enhances repair of UV-damaged DNA by
altering the organizational structure of DNA.
Project description: Mr Wong is studying the role of the tumour suppressor INGlb in DNA repair.
He will determine how INGlb is able to change DNA organization to enhance DNA repair. He will
use a human melanoma cell culture system to carry out this study so that he will be able to
understand DNA repair in human cells.
Impact and significance: It is important to understand how cells repair damaged DNA to protect
cells from cancer development. As the tumour suppressor INGlb is frequently altered in many
cancers, understanding how it is involved in DNA repair, may enable the design of new
strategies to prevent cancer development in susceptible individuals carrying INGlb alterations.
Mr Wong may also be able to design early detection markers for cancer development.
Melanoma is notorious for being difficult to treat. By understanding how melanoma cells repair
DNA, he may be able to design strategies to improve the efficacy of chemotherapy in
melanoma patients.
Category of Research: Fundamental research
Cancer Site Relevance: Skin/integument
Yang, Ziqiang
TFF Research Fellowship - Biomedical 40,833
New & Continuing TFF Awards in 2008/2009
Principal Investigator, Host Institution, Title
Grant Type
$ Awarded
2008/2009
Ontario Cancer Institute/PMH, Toronto, Canada
The role of the Gab1/PAR-1b complex in control cell polarity
Dr Ziqiang Yang obtained his PhD at Peking University. He is now conducting his postdoctoral
research training in developmental biology under the supervision of Dr Benjamin Neel at the
Ontario Cancer Institute/Princess Margaret Hospital.
Project summary: The establishment and maintenance of cell polarity are crucial biological
processes required both for normal cell function and development. Disruption of cell polarity is a
common feature of disease states including tumour metastasis and invasion. In this proposal,
he will study how cell polarity is regulated and how normal cell polarity is altered in cancer cells.
Previous research: Cell polarity has been extensively studied in both worms and mammalian
cells. One protein, termed PAR-lb, was found to play an important role in cell polarity control.
How PAR-lb functions is not fully understood. Recently, it was found that another signaling
protein, Gab1 forms a complex with PAR-1b in mammalian cells.
Project description: Dr Yang is studying the mechanism of cell polarity, deregulation of which is
an important process in cancer development. In this study, he will further characterize the
GablPAR-lb complex and define its biological role in both normal and cancer cells. A better
understanding of how polarity is changed in cancer cells will lead to improved treatment of
human cancers.
Impact and significance: Loss of polarity is a crucial step in cancer metastasis and invasion.
Thus an understanding of cell polarity regulation will be essential for understanding the
mechanism of cancer invasion. This study will contribute to a better understanding of normal
polarity regulation, as well as the mechanism of tumour metastasis, and ultimately, might help in
designing new effective cancer therapies.
Category of Research: Fundamental research
Cancer Site Relevance: Various cancer sites
Yip, Kenneth
TFF Research Fellowship - Biomedical 42,398
Burnham Institute (The), La Jolla, USA
Chemical activators of PML and Daxx for cancer therapy