Page 1 of 31
Comprehensive Research Experience for Medical Students
2014 Research Scholar Program
Available Projects
Instructions:
1. If you are interested in working with one of these supervisors on the project outlined, contact the supervisor to
arrange a meeting with them to discuss further;
2. If an agreement is made between you and the supervisor to work together, the supervisor must complete the
Mentor Agreement Form (found on CREMS website) and send via email to Lisa Charrette, CREMS
Coordinator at crems.programs@utoronto.ca by end of day November 27, 2013.
3. The Mentor Agreement Form will be attached to the complete project information form that the supervisor has
already completed and will be reviewed by the CREMS Advisory Committee.
4. Applicants will be notified if their projects will receive funding by mid-December.
Good Luck!
Page 2 of 31
SUPERVISOR: Alan Moody: FRCR, FRCP - Professor
TELEPHONE: 647-282-1244
EMAIL: alan.moody@sunnybrook.ca
 FIELD OF RESEARCH: Imaging; Atheroma
 DEPARTMENT: Medical Imaging
PROJECT TITLE: Tomorrow Project – Carotid Imaging Core Laboratory
PROJECT DESCRIPTION
The Tomorrow project is a national project recruiting volunteers with in depth clinical data, bio-diagnostic work up and in
10,000 patient’s comprehensive whole body imaging. Part of the imaging will be the assessment of vascular disease by the
imaging of carotid vessel wall characteristics. 10,000 patients (20,000 carotid arteries) will be assessed in our core lab. These
volunteers will span the ages of 45-70. We know that vascular aging results in increased vessel wall thickness but this has not
been comprehensively studied in large cohort studies. The development of pathological features through these age ranges
including lipid deposition, calcification and wall hemorrhage.
STUDENT ROLES & RESPONSIBILITIES
 Supervision of data collection and collation in core imaging lab
 Undertaking database construction
 Data analysis
 Imaging analysis
 Project presentation and write up
Page 3 of 31
SUPERVISOR(S): Narinder S. Paul MD, MRCP (UK), FRCR (UK), FRCPC - Associate Professor
Elsie Nguyen MD, FRCPC – Assistant Professor
TELEPHONE: 416-340-4800 ext. 3422
EMAIL: narinder.paul@uhn.ca
 FIELD OF RESEARCH: Coronary Artery Disease; Women
 DEPARTMENT: Medical Imaging
PROJECT TITLE: Coronary Artery Disease in Women
PROJECT DESCRIPTION
Coronary artery disease is the leading cause of death in women globally. Women are more likely to present with atypical chest pain and are less
likely to reach target heart rate during traditional exercise electrocardiographic (ECG) stress testing, posing challenges to investigation of chest
pain by traditional methods. Furthermore breast attenuation can cause false positive results on nuclear medicine perfusion scans. Dobutamine stress
echo evaluates contractile reserve and identifies stress induced wall motion abnormalities but cannot exclude coronary artery disease. In contrast,
coronary computed tomography angiography (CTA) has high negative predictive value (NPV=99%) for exclusion of coronary artery disease in low
to intermediate risk populations. Radiation dose associated with coronary CTA is now significantly lower than radiation doses associated with
nuclear medicine perfusion scans or diagnostic catheter angiograms owing to recent technologic advances. We hypothesize that using coronary
CTA as a first line modality to exclude coronary artery disease as a cause of stable chest pain in women is a cost effective strategy that significantly
reduces downstream testing as compared to standard of care (using treadmill exercise ECG stress testing, dobutamine stress echocardiography or
nuclear medicine perfusion scanning).
A unique multidisciplinary program has recently been initiated at Women’s College Hospital whereby family physicians, cardiologists and
radiologists work in close collaboration to investigate women with chest pain or other symptoms potentially attributable to coronary artery disease.
Our innovative strategy places coronary CTA early in the diagnostic algorithm to exclude coronary artery disease as the cause of chest pain.
Consequently, family physicians will only refer patients to cardiologists who have documented coronary artery disease by coronary CTA. As a
result, there will be improved resource utilization and also reduction in wait times to see cardiologists in consultation as patients without coronary
artery disease excluded by coronary CTA will be removed from this pool of patients. Over a period of 2 years, data will be collected for a case
cohort comparative study between coronary CTA as a first line imaging modality and current standard of care involving ECG stress testing, stress
echocardiography and nuclear medicine perfusion scanning. Overall costs, frequency of downstream testing, patient satisfaction and comfort level
will be compared among the two groups.
STUDENT ROLES & RESPONSIBILITIES

Create a database using Microsoft Access or similar software program to keep track of all the coronary CTA cases performed as part of
the Women’s Cardiac Health program at Women’s College Hospital

Maintain the database during the 20 month period (5 cases per week currently but numbers will likely increase in the next year as the
referral base increases)

Literature review of coronary artery disease in women and gender differences

Be first or second author on a paper or several papers as a result of the data collected
Page 4 of 31
SUPERVISOR(S): Svetlana (Lana) Popova MD, PhD, MPH – Assistant Professor
TELEPHONE: 416-535-8501 ext. 4558
EMAIL: lana.popova@camh.ca
 FIELD OF RESEARCH: Epidemiology; FASD
 DEPARTMENT: Epidemiology
PROJECT TITLE: World Health Organization International Study on Child Development and Prenatal Risk Factors:
Canadian Component
PROJECT DESCRIPTION
The Centre for Addiction and Mental Health (CAMH), home to the largest mental health and addictions research facility in Canada is conducting a
research study on child development in the Greater Toronto Area (GTA) in Ontario, Canada.
A research team (Principal Investigator: Dr. Svetlana Popova), from the Social and Epidemiological Research Department at the CAMH will examine the
prevalence of neurodevelopmental disorders (such as Fetal Alcohol Spectrum Disorder, Attention Deficit Hyperactivity Disorder, Autism, Conduct
Disorder and other disorders) in the context of pregnancy conditions including maternal nutrition, living environment, alcohol and tobacco use. This will
be achieved by screening approximately 8,000 elementary school students across the GTA.
This study is supported by Public Health Agency of Canada (PHAC) and has been recognized as a national strategic focus. It has received the attention of
the federal Minister of Health, the Honourable Leona Aglukkaq, and was announced by the Ministry of Health on February 21, 2013.
This project is also part of a large international study being conducted under the auspices of the World Health Organization (WHO), which is seeking to
examine the prevalence of neurodevelopmental disorders in more than 10 low and middle income countries, in addition to Canada.
This is a very important study and it will be the first study in Canada to estimate the prevalence of neurodevelopmental disorders among elementary
school students using the best available method at this point in time (i.e., a population-based method, active case ascertainment). This project will
generate new data on the prevalence of neurodevelopmental disorders among elementary school students and contribute to the development of monitoring
frameworks in Canada and globally.
STUDENT ROLES & RESPONSIBILITIES

Collect information from the participants (physical examination & behaviour history of children).

Work with the psychologist to collect information from the participants (neuropsychological/developmental assessment)

Work with dysmorphologist to examine participants on dysmorphological features associated with prenatal alcohol exposure

Collect data on maternal prenatal alcohol exposure history from biological mothers of children with suspected FASD.

Perform analysis of the information obtained

Prepare results of the study for dissemination (report, peer reviewed publications).
Page 5 of 31
SUPERVISOR(S): Khosrow Adeli PhD
TELEPHONE: 416-813-8682
EMAIL: khosrow.adeli@skickkids.ca
 FIELD OF RESEARCH: Laboratory Medicine; Biochemistry
 DEPARTMENT: Laboratory Medicine and Pathobiology
PROJECT TITLE: The CALIPER Project: Establishing Pediatric Reference Intervals for Laboratory Biomarkers of
Pediatric Disease
PROJECT DESCRIPTION
Healthcare delivery is critically dependent on the availability of accurate and precise laboratory tests/biomarkers of disease, and on the availability
of ‘reference intervals’—values that can be expected to be found in normal, healthy individuals against which test results can be compared.
Unfortunately, there is a lack of clearly defined, representative reference intervals for most tests performed in children and adolescents. There is
also a paucity of information on the effects of age, sex, and ethnic origin on these reference values, making clinical application of existing
reference ranges difficult in diverse populations. These critical gaps seriously compromise the ability of physicians to accurately diagnose medical
conditions in their patients, significantly increasing both the medical and economic costs. It is thus critical a comprehensive database of covariatestratified reference intervals be established in the diverse Canadian population. The CALIPER Project: The CALIPER Project (Canadian
Laboratory Initiative on Pediatric Reference Intervals) is a national collaboration between seven pediatric centres across Canada intended to close
these critical gaps. A major community outreach and recruitment effort has led to the development of reference intervals for more than 70
chemistry, endocrine, and fertility assays so far in a population of children and adolescents sampled in the Greater Toronto Area.
In the most recent phase of the project, the CALIPER group has gained access both to data and samples collected through The Canadian Health
Measures Survey (CHMS). Launched in 2007 by Statistics Canada, CHMS has established a large database of key information relevant to the
health of Canadians. The survey has evaluated a representative sample of the Canadian population age 3 to 79 years living in the ten provinces and
the three territories. Items assessed include direct physical measurements such as blood pressure, height, weight, and physical fitness. In addition,
the survey has collected blood and urine samples. While some of these samples have been analyzed for a number of key analytes and biomarkers,
CALIPER has also gained access to the samples themselves for testing of additional analytes of interest. Though CALIPER has made significant
strides in the previous few years in terms of developing reference intervals, the use of CHMS data is advantageous for two reasons: 1) The sample
size is very large, ensuring that reference intervals for all age and sex groups will have sufficient statistical power, and 2) CALIPER samples have
been predominantly collected within the Greater Toronto Area, whereas CHMS data provides a representative sample of the entire Canadian
population, meaning that resulting reference intervals can be applied in laboratories across Canada.
While a number of projects have been planned in collaboration with Statistics Canada, the objective of the current proposal, over the following
two years, is to establish pediatric reference intervals for vitamin A, E, B12, and folate. Reference intervals will be developed for individuals
aged 3 to 19 years, and will be determined with appropriate stratification based on age, sex, and ethnic origin.
Page 6 of 31
STUDENT ROLES & RESPONSIBILITIES

Data Collection: Statistics Canada possesses very particular guidelines for collection and storage of data relating to CHMS samples. The
medical student will be responsible for learning these guidelines, acquiring access to the centralized Research Data Centre (RDC) where
sample information is stored, and for coordinating with Statistics Canada and RDC employees to ensure appropriate data collection and
management.

Clinical Laboratory Diagnostic Testing: Samples acquired from CHMS will be analyzed on instruments located at The Hospital for Sick
Children for levels of vitamin A, E, B12 and folate. Acquisition of data must be completed according to Statistics Canada guidelines and
transmitted back to officials for integration with CHMS survey data, which is stored on computers located at the RDC. The medical
student will be involved in helping to set up the infrastructure required to test samples at the Hospital for Sick Children, will observe
clinical testing, and will help to coordinate data transfer.

Data Analysis: Following the data collection phase, the student will work from the RDC to establish reference intervals for vitamins A, D,
E, B12 and folate. With the help of the CALIPER team’s biostatistician, the student will apply exclusion criteria and outlier removal to
data, will learn to apply appropriate partitions based on age, sex, and ethnicity-related trends in data, will test the significance of
partitions, and will ultimately develop reference intervals that are representative of the diverse Canadian population to be applied in
clinical laboratories across the country.

Publication and knowledge translation: Results of the study will be written up by the student for publication in a peer review journal and
for presentation at various professional conferences. Given that appropriate, representative reference intervals are integral to the
interpretation of laboratory results and, therefore, to accuarate and efficient medical care, the primary focus of CALIPER has been on
knowledge exchange and translation throughout. Thus, study results will also be made available for free in several formats, including: in
package inserts for relevant laboratory testing instruments; via an established CALIPER website (www.caliperdatabase.com) which
receives more than 15,000 unique hits per month from clinicians and laboratory professionals seeking out existing CALIPER data; on a
smart phone application currently entering the testing phase, made available on Android and Apple (iOS) operating systems to facilitate
easy and rapid access to reference interval data. The student will have an integral role in preparing data for all phases of the publication
and knowledge translation process.
Page 7 of 31
SUPERVISOR(S): Anne Bassett MD, FRCPC - Professor
TELEPHONE: 416-535-8501 ext. 32731
EMAIL: anne.bassett@utoronto.ca
 FIELD OF RESEARCH: Genetics; Developmental Diseases
 DEPARTMENT: Psychiatry
PROJECT TITLE: Translating genetic research findings for major developmental conditions into clinical practice
PROJECT DESCRIPTION
We study major developmental diseases, congenital cardiac disease and schizophrenia and common but under-recognized
syndromes e.g. 22q11.2 deletion syndrome. We are clinically screening patients with these conditions and their relatives to
determine those most likely to have genetic syndromes and new genetic changes or inherited forms of disease. Working with
colleagues at The Centre for Applied Genomics we are using state-of-the-art molecular genetic methods (e.g. genome-wide
microarrays and sequencing), to identify structural and sequence-based changes and study inheritance patterns. We directly
translate clinically significant results to help patients and their families. This is clinical and statistical (not bench lab) genetic
research at the forefront of molecular medicine.
STUDENT ROLES & RESPONSIBILITIES
 Select a feasible project
 Conduct the related clinical research by obtaining and analyzing data
 Present scholarly work as a poster and/or oral presentation
 Write one or more first author peer reviewed papers (with supervision)
Page 8 of 31
SUPERVISOR(S): Sam Doesburg PhD – Assistant Professor
TELEPHONE: 416-813-2182
EMAIL: sam.doesburcg@sickkids.ca
 FIELD OF RESEARCH: Neuroscience; Neurophysiology
 DEPARTMENT: Neuroscience
PROJECT TITLE: Delineating epileptogenic cortex using network connectivity measures
PROJECT DESCRIPTION
In focal drug-resistant epilepsy, surgical removal of brain regions responsible for starting seizures is often the most effective available treatment.
The location and extent of this epileptogenic zone is quite heterogenous in childhood neocortical epilepsy. Accordingly, accurate delineation of
epileptogenic cortex is often elusive using current methods. The gold standard for identifying epileptogenic brain regions is ictal
electrocorticography (ECoG), which involves analysis of recordings from surgically implanted electrodes. It has become increasingly apparent that
altered interactions among brain regions, or functional network connectivity, are present within the epileptogenic zone.
Previously, we have identified frequency-specific alterations in the inter-electrode synchronization of brain rhythms which are associated with
epileptogenic cortex. We have developed a toolbox for analyzing and animating the dynamics of inter-electrode connectivity in ECoG recordings
during seizures. The present project will be to use this toolbox to identify attributes of functional connectivity dynamics which may be biomarkers
of epileptogenic cortex. The sensitivity and specificity of these network measures will then be evaluated to determine if the identified network
measures have presurgical mapping utility. A complementary goal will be to better understand the role of neurophysiological interactions in brain
networks in childhood epilepsy.
STUDENT ROLES & RESPONSIBILITIES
The student will analyze ECoG data recorded from patients undergoing neurosurgery at the Hospital for Sick Children. This work will be
facilitated by analysis techniques recently developed by the research team. The student will carry out research to identify alterations in functional
brain connectivity, and its dynamics, associated with epileptogenic cortex. The sensitivity and specificity of any network measures identified will
be assessed by the student, to determine if identified alterations associated with epileptogenic cortex have presurgical mapping utility. If this work
yields new insights into the neurophysiology of epilepsy, or identified new approaches for presurgical mapping, the student will be expected to
participate in the preparation of results for publication. This will provide the student an opportunity to work alongside clinical neuroscientists, as
well as residents and fellows involved in pediatric neurology and neurosurgery, on a highly clinically-relevant research topic.
Page 9 of 31
SUPERVISOR(S): Seema Mital MD – Associate Professor
TELEPHONE: 416-813-7418
EMAIL: seema.mital@sickkids.ca
 FIELD OF RESEARCH: Congenital heart disease; Genomics and stem cells
 DEPARTMENT: Cardiology
PROJECT TITLE: Genetic guided therapy in transplant
PROJECT DESCRIPTION
The student will work on genomic and clinical data available in SickKids Heart and Transplant Centre Biobank (PI, Mital) which has enrolled
>5,000 children (and adults) with heart disease and after solid organ transplant. Children after transplant are on multiple medications for their
lifetime. These medicines can have significant side-effects including infections, cancer, viral disorders, hypertension, and other side effects. One of
the goals is to identify how pharmacogenetics influences safety and response to drugs used after transplantation and to use this knowledge to
develop personalized dosing for each child. We are collecting clinical and genomic data on over 400 transplant patients enrolled in our biobank
with additional patients being recruited through a national research program. This data will be available to the student to perform this project.
STUDENT ROLES & RESPONSIBILITIES

Project development

Data collection from prospectively enrolled patients through questionnaires and chart reviews

Data entry

Data analysis

Writing scientific abstract

Presentation, writing and publishing scientific manuscript
Page 10 of 31
SUPERVISOR(S): Maria Mylopoulos PhD – Assistant Professor
TELEPHONE: 416-813-7654 ext 203126
EMAIL: maria.mytlopoulos@utoronto.ca
 FIELD OF RESEARCH: Cognitive Psychology
 DEPARTMENT: Pediatrics
PROJECT TITLE: ‘Quality’ of the Safe Surgery Checklist performed at a tertiary care academic hospital in Canada:
an in-depth gap analysis and needs assessment
PROJECT DESCRIPTION
The Safe Surgery Checklist (SSCL) is a global initiative supported by the World Health Organization to improve safety in surgery. In 2010, the SSCL became a
Ministry of Health and Long Term Care (MOHLTC) publicly mandated patient safety indicator. As a result, all Ontario hospitals are now required to report their
compliance rates with the SSCL, which are published by the provincial government.
However, at present there is little research directed at the quality of the safety checks that are being performing in operating rooms (ORs) around the world. By
definition, the SSCL is considered ‘performed’ when ‘the surgical team members have addressed all of the necessary tasks and items in each of the three phases,
‘briefing’, ‘time out’ and ‘debriefing’ of the checklist’. In the briefing section alone, there are over 14 items requiring confirmation (e.g. patient identification,
pre-induction concerns, allergies, medications etc.). Existing compliance data simply notes completion for each of the 3 phases, without consideration of the
various sub-components of each phase, nor the quality of communication between members of the operative team.
Compliance data from the Hospital for Sick Children (HSC) indicates significant variability in SSCL compliance among surgical services and depending on the
nature of the operation (e.g. emergency vs. elective). A number of anecdotal reports also suggest that even where OR teams are ‘compliant’ (i.e. the 3 phases are
completed), often the check is not conducted to the standard outlined by the SSCL. In some instances, significant medical errors have resulted despite the safety
check having been ‘completed’.
The current project is a collaboration among researchers, clinicians and quality improvement/patient safety staff at HSC. The purpose of this project is to
document and understand variations in the practice of the surgical safety check among surgical teams at the HSC. There are three phases to the project:
a) Observe team performance during the use of the SSCL to identify adherence and proper use, using an assessment tool developed by the research team as well
as qualitative participant observation
b) Interview surgical team members to understand the nature and rationale for variations from practice when using the SSCL, and which variations are
‘acceptable’ or ‘not-acceptable’ (i.e. would potentially lead to compromised patient safety)
c) Develop targeted interventions directed at variations in practice that are deemed ‘not acceptable’ to improve the quality of the SSCL performed by surgical
teams.
Data collection for the first phase of the project is complete, including observations of over 50 surgical cases. The next phase of the project involves analysis of
quantitative and qualitative data generated from these observations, as well as development of an interview guide and completion of semi-structured interviews
with surgical team members (nurses, surgeons and anesthesiologists) to help contextualize the findings from the observational phase. Interviews will be audio
recorded and transcribed verbatim to facilitate data analysis. It is anticipated that the results of these two phases will be disseminated through publication in a
peer-reviewed academic journal focusing on patient safety and quality improvement of healthcare services (e.g. International Journal for Quality in Healthcare)
Page 11 of 31
STUDENT ROLES & RESPONSIBILITIES
The medical student participating in this project will be primarily responsible for analyzing and interpreting the data collected during the
observation phase of the study, with the support of the research supervisor and additional members of the research team. The specific
responsibilities will include conducting statistical analyses (descriptive and inferential) on the quantitative data generated from the assessment tool
used during the observations, as well as qualitative analysis of field notes taken by the observers.
Once this is complete, the student will generate a preliminary interview guide for the semi-structured interviews based on patterns observed during
the observations, and with the support of the research team will recruit and complete semi-structured interviews with 12-15 surgical team members.
Once the interviews are transcribed (3rd party transcription), the student, supervisor, and select members of the research team will conduct initial
coding and iterative thematic analysis of the transcripts. Finally, the student will have the opportunity to take the lead on drafting a manuscript for
submission to a peer-reviewed journal and presentation of the results at local, national, and international meetings to disseminate the results of the
study.
Page 12 of 31
SUPERVISOR(S): Donald Redelmeier MD - Professor
TELEPHONE: 416-480-6999
EMAIL: dar@ices.on.ca
 FIELD OF RESEARCH: Medical Decision Science; Motor Vehicle Trauma
 DEPARTMENT: Internal Medicine
PROJECT TITLE: Medical Decision Science
PROJECT DESCRIPTION
My group conducts an eclectic program of research focusing on how people reason, formulate judgments, and make decisions.
We have conducted multiple studies on errors in medical decision making, with particular attention to general internal
medicine. A secondary theme examines motor vehicle trauma, another domain where mistakes in reasoning can have
irreparable consequences. Most projects are based on statistical methods and other dry-bench forms of methodology. Specifics
projects depend on the interests of the student and my mood at the time.
STUDENT ROLES & RESPONSIBILITIES

Conception and design

Literature review

Ethics submissions

Data collection

Results interpretation

Manuscript preparation and scientific peer review
The student is expected to integrate with the full academic group, attend seminars, and give feedback to others on other projects.
The specific project for this student is substantial and requires the full 20 months for completion (perhaps a bit longer due to vagaries of peerreview medical journals). The project will be judged complete on publication of an article and addressing follow-up knowledge translation
activities (e.g. scientific presentations, letters-to-the-editor, media interviews).
Page 13 of 31
SUPERVISOR(S): Paul Arnold MD, PhD – Associate Professor
TELEPHONE: 416-813-7530
EMAIL: paul.arnold@sickkids.ca
 FIELD OF RESEARCH: Genetics; Obsessive Compulsive Disorder
 DEPARTMENT: Psychiatry
PROJECT TITLE: Genetic Determinants of Childhood Obsessive-Compulsive Disorder (OCD)
PROJECT DESCRIPTION
Research in my lab is focused on finding risk genes for childhood OCD, a common and debilitating neuropsychiatric disorder.
We are currently engaged in three major related projects: 1) A province-wide study looking a neuropsychiatric disorders in
children, including OCD, ADHD and ASD 2)A genome-wide association study of obsessive-compulsive traits in a large
general population sample, and 3) An “imaging genetics” study in which we are studying the influence of candidate genes on
neuroimaging phenotypes in a clinical sample of children with OCD.
STUDENT ROLES & RESPONSIBILITIES
Interested students would potentially have the opportunity to learn a variety of research methods including basic statistical
analysis of genetic and clinical data, and wet lab (genotyping) techniques depending on their interests and career goals.
Opportunities to observe behavioural assessments in a clinic setting will also be available.
Page 14 of 31
SUPERVISOR(S): Onil Bhattacharyya MD, PhD – Associate Professor
TELEPHONE: 416-323-6244
EMAIL: onil.bhattacharyya@wchospital.ca
 FIELD OF RESEARCH: Knowledge Translation; Innovation
 DEPARTMENT: Family Medicine
PROJECT TITLE: SCOPE 2 – Seamless Care Optimizing the Patient Experience – A randomized control trial to
reduce Emergency Department use by patients of community-based solo family doctors
PROJECT DESCRIPTION
SCOPE2- Seamless Care Optimizing the Patient Experience is a partnership between Women’s College Hospital (WCH), Mount Sinai Hospital
(MSH), University Heath Network (UHN) and the Toronto Central Community Care Access Centre that integrates primary, acute and community
care by targeting Primary Care Physicians (PCPs) whose practices are located in the Mid-West Toronto Health Link. SCOPE has been designed to
enhance and expand the organization of the ‘primary health care team’ by supporting community-based practitioners and their patients with
complex medical needs. The SCOPE2 project builds upon the SCOPE project which has been very well received by community PCPs.
Evaluation of this initiative is being conducted as a randomized control trial (RCT) by a separate team of researchers across the Departments of
Medicine and Family and Community Medicine at the University of Toronto (Principle Investigator Dr. Onil Bhattacharyya, WCH). The
evaluation is funded by the Ontario Ministry of Health and Long-Term Care (MOHLTC) via the Health System Research Fund (HSRF) Program
Awards. The HSRF Program Awards provides strategic three-year investments to policy relevant programs of health research that focus on
identified government priorities such as primary care integration.
STUDENT ROLES & RESPONSIBILITIES
We will be conducting rapid cycle testing as part of the data collection/analysis process. The student will work with the team to develop testable
hypotheses and determine what type of data is required to test the hypothesis. Then, the student will be responsible for collecting appropriate
qualitative and quantitative data, analyzing it, and presenting the data analysis to the team for further inquiry and refining. The student will be
asked to adapt to conducting research using an agile process and integrate design thinking into their work.
Page 15 of 31
SUPERVISOR(S): Gillian Hawker MD, MSc - Professor
TELEPHONE: 416-323-7722
EMAIL: g.hawker@utoronto.ca
 FIELD OF RESEARCH: Health Outcomes; Osteoarthritis
 DEPARTMENT: Rheumatology
PROJECT TITLE: Quality of Care for People with Osteoarthritis
PROJECT DESCRIPTION
Osteoarthritis (OA) is the most common arthritis, affecting 1 in 8 Canadians. OA causes progressive joint pain, disability, fatigue, and depressed mood.
Although effective management strategies for OA exist, substantial under-treatment of painful OA has been documented due to the perception that OA is a
normal part of aging, that no effective treatments exist, and the high prevalence of other chronic conditions, like heart disease, which increase the risk of side
effects when OA therapies are used.
Prior research in a subset of Women’s College Hospital Family Health Team follow-up patients, funded by Health Canada through its primary care surveillance
strategy, documented a high prevalence of patients with persistent joint complaints (indicating on a homunculus that one or more joints had been painful,
swollen or stiff on most days of the previous month); the majority of these patients did not have a recorded arthritis diagnosis and had not received
recommended arthritis treatments. The current project is a quality improvement initiative designed to address these care gaps.
Under the supervision of Dr Hawker, and working with Women’s College Research Institute (WCRI) - affiliated clinician researchers in family medicine (Drs
Noah Ivers and Sheila Dunn), the student will: 1. Participate in a quality improvement project to improve the quality of care for Family Health Team patients
with diagnosed OA. For patients who have been identified a priori as having OA, a mail/online survey will be conducted to assess current OA care against
validated OA quality indicators and OA symptom severity (WOMAC questionnaire). Results will be fed back to their primary care physician, along with
recommendations to address identified gaps. Using PDSA (Plan-Do-Study-Act) cycles, our feedback approach will be refined with the goal of improving overall
OA care quality and the quality of the patient experience.
Together, we believe the combination of participation in a hands-on quality improvement initiative, and the opportunity to get involved in hands-on clinical care,
will inspire the student to become involved in clinical research.
STUDENT ROLES & RESPONSIBILITIES
We hope to cultivate an understanding of the role of, and challenges in, primary care management of osteoarthritis. The project will provide the student with an
excellent clinical research and training opportunity. Under the guidance of an experienced clinical research program with support from investigators, research
associates and statisticians, the student will be immersed in the research environment. The student will be guided through data collection, statistical analysis and
interpretation of results. The student will develop integral skills to becoming a clinical researcher as well as insight into their interest and suitability for a career
path in academic medicine. Finally, the project will provide the student with an evidence-based understanding of arthritis disability and its prevalence in the
population. The student will be encouraged to attend seminars, rounds and research meetings and present the results of their work. Abstracts for presentation at
annual rheumatology conferences will be prepared in addition to the final publication.
Page 16 of 31
SUPERVISOR(S): Bernard Le Foll MD, PhD, CCFP - Professor
TELEPHONE: 416-535-8501 ext. 4772
EMAIL: bernard.lefoll@camh.ca
 FIELD OF RESEARCH: Pharmacology; Addiction
 DEPARTMENT: Family & Community Medicine, Pharmacology, Psychiatry
PROJECT TITLE: Clinical or Preclinical approaches to improve addiction treatment
PROJECT DESCRIPTION
Translational Addiction Research Laboratory
The main goal of the Translational Addiction Research Laboratory is to improve the treatment and understanding of drug addiction. The research aims at linking
discovery in basic science to clinical applications. The research is organized over three main areas of research:
1.
2.
3.
Role of dopamine receptors in additions: We have identified a role of the dopamine D3 receptor on nicotine-seeking behaviors. We are exploring
the role of D3 (and other DA subtypes) in various addictions and collaborate with Dr Boileau to use PET imaging to explore dopamine transmission
and D3 in human subjects.
Role of cannabinoid system in addictions: We have identified that cannabinoid drugs modulate nicotine-seeking behaviors. We are exploring novel
cannabinoid ligands in preclinical models of addictions and the impact of cannabinoid drugs in humans.
Role of insular cortex in addiction: We have identified that insular cortex controls nicotine-seeking and we are exploring the role of insular cortex in
other addictive behaviors (alcohol/gambling). The role of insular cortex is being explored in humans using rTMS and brain imaging approaches
Alcohol Research and Treatment Clinic
As part of the Addiction Medicine Service of the Centre for Addiction and Mental Health, the Alcohol Research and Treatment Clinic (ARTC) brings together
an inter-professional team of physicians, nurses and specialized therapists to improve access to pharmacotherapies for the treatment of alcohol dependence. Led
by Dr. Bernard Le Foll, the clinic also includes research and evaluation components to find new evidence-based treatment strategies that will inform delivery of
care at CAMH, throughout the province and beyond. ARTC is currently using approved pharmacotherapies (disulfiram, naltrexone and acamprosate) and second
lines therapies (baclofen and topiramate).
Below is a selection of some of the research projects that are ongoing:
1.
2.
3.
Pharmacotherapies for impaired drivers: We are exploring the utility of naltrexone in subjects convicted of impaired driving with alcohol
dependence.
Smoking cessation during alcohol treatment: in collaboration with Dr Zawertailo and Dr Selby, we are exploring the utility of varenicline for
smoking cessation in subjects with alcohol dependence.
Improving pharmacotherapies for alcohol dependence: In collaboration with Dr Daskalakis, we explore the impact of drugs on brain function.
STUDENT ROLES & RESPONSIBILITIES
Being involved in one of the project that is running through the Translational Addiction Research Laboratory or the Alcohol Research and Treatment Clinic, the student
will learn to perform research and be involved with our senior team in a project and will participate in results writing and analysis
Page 17 of 31
SUPERVISOR(S): Chung-Wai Chow MD, PhD – Assistant Professor
TELEPHONE: 416-340-3512
EMAIL: chung-wai.chow@uhn.ca
 FIELD OF RESEARCH: Air Pollution; Lung Transplantation
 DEPARTMENT: Medicine
PROJECT TITLE: Traffic-related Air Pollution and the Transplanted Lung
PROJECT DESCRIPTION
Our group and another in Belgium retrospectively assessed 421 and 288 LTx recipients, respectively, and found that living in a high traffic density area was associated with
increased risk of chronic allograft dysfunction and mortality. Neither study measured specific pollutants but instead, inferred TRAP exposure in terms of the proximity of
patients’ residence to traffic.
Direct personal measurements of the TRAP exposure will help better establish associations between disease and TRAP, and facilitate investigations of the mechanisms that lead
to disease. However, the optimal method for evaluating pollutant exposure and the identity of the pollutant constituents most relevant to disease pathogenesis are not known.
We postulate the adverse health impact of air pollutants on health can be best understood through an integrated assessment of exogenous exposure, endogenous uptake and
clinical outcome.
In this project, we will conduct a comprehensive assessment using a cohort of LTx recipients.
The objectives are: 1) to evaluate associations between exogenous levels of pollutants measured through personal, in-home and central site monitoring with endogenous levels
of pollutant uptake [in bronchoalveolar lavage fluid (BALF), urine and blood], 2) to identify inflammatory mediators in BALF, assess association of inflammatory mediators
with pollutant concentrations and 3) maximal lung function attained at 2 years following LTx.
LTx is an ideal clinical model in this context. Although their graft is normal at the time of transplantation, these patients have a high risk of developing airway disease, a risk that
begins immediately post transplantation. Furthermore, the routine close clinical follow-up of this patient population allows us to clearly identify the extent of exposure to
pollutants over time, and identify onset and timing of disease development.
We will prospectively recruit 80 patients undergoing LTx over 5 years at the Toronto Lung Transplant Program. We will characterize pollutants measured through four
exogenous exposure and endogenous pollutant uptake assessment techniques: (i) in BALF, urine and blood, via (ii) personal monitoring, (iii) in-homes monitoring, and (iv)
central site monitoring. Personal and in-home monitoring is scheduled around routine surveillance bronchoscopies and clinic visits in the initial 3 months post-transplant.
Patients are followed very closely as they are most vulnerable to developing complications during this period. Personal monitoring and BALF collection will continue until 2
year postLTx. Patients are followed for life with regular clinic visits, pulmonary function studies and laboratory studies.
We will use the data to identify associations between exogenous and endogenous measures of pollutant exposure, as well as exposure measurements and biomarkers of
pathophysiological response. This will allow us to develop a comprehensive exposure assessment protocol that can be employed in large prospective studies to assess the
relationship of pollutant exposures with clinical outcomes in LTx and other large patient populations at risk of the adverse effects of TRAP.
STUDENT ROLES & RESPONSIBILITIES

Recruitment of patients in the pre-lung transplant clinic

Follow-up with interested patients in hospital immediately following transplant (i.e. during the hospital for the transplantation). This visit is designed to exclude
patients who will not be eligible to participate in the study because they do not meet inclusion criteria

Subsequent participation in home visit of patients at 6 and 12 weeks post-transplant. During these home visits, the student and study coordinator will drop off and
pick up (1 week later) pollution monitoring equipment, conduct a home survey to look at potential sources of pollutants, review the patient activity logs, and review
home spirometry data

The home visits are followed by collection and review of clinical parameters that may potentially be affected by air pollution. In other words, the students will do
chart review of the patient whom she/he has conducted the home visit

The student will also participate in the collection of blood, urine and bronchoalveolar lavage fluid that is collected during the intensive pollution monitoring period.

At the end of the research period, the student will be expected to participate in analysis of data and write up of reports, abstracts and manuscripts
Page 18 of 31
SUPERVISOR(S): Kenneth Croitoru MD - Professor
TELEPHONE: 416-586-4800 ext 7454
EMAIL: kcroitoru@mtsinai.on.ca
 FIELD OF RESEARCH: IBD; Mucosal Immunity
 DEPARTMENT: Medicine
PROJECT TITLE: Role of IL23 in control of intestinal microbiota
PROJECT DESCRIPTION
Inflammatory bowel disease (IBD) is thought to be due to an abnormal host immune interaction with intestinal microbiota in a genetically susceptible individual.
One genetic risk allele for IBD is the IL23 receptor (IL23R), important in the control of inflammatory Th17 T cells. We recently showed that the IL23R SNP,
rs11209026 (R381Q), is associated with an altered gut microbiota in healthy first-degree relatives at risk of developing Crohn’s disease. This suggests an
important role for IL23/IL17 pathway in the modulation of commensal bacteria and suggests a mechanism by which host genetics influence the development of
Crohn’s disease. This project will aim to define the mechanism by which IL23R polymorphisms alter the gut microbial makeup by utilizing mice deficient for
the IL23R.
Aim 1 of this study will be to define and compare the intestinal microbiota of IL23R deficient mice with wild type controls using next generation sequencing of
the prokaryotic 16S rRNA gene. Stool and mucosal microbial DNA will be sequenced using Illumina MiSEq and taxonomic assignments of the sequences will
be assessed for changes in relative abundance of the major bacterial genera.
Aim 2 will seek to determine if the intestinal microbiota of IL23R deficient mice respond differently to the effect of broad spectrum antibiotics and if the
microbiota in these mice differ in their ability to recover after withdrawal of the antibiotics.
In both of these aims we will measure the response of Th17 T cells to gut bacteria and in aim 2 this will be done both before and after antibiotic therapy. These
experiments will define the role of IL23R and the IL23/Th17 pathway in controlling the make-up of the commensal microbiota in the gut. These results will be
important in defining the role of mutations in Il23R / Th17 pathway in setting the stage for the development of IBD.
STUDENT ROLES & RESPONSIBILITIES
The student will be responsible for extracting bacterial DNA from stool and mucosal samples of Il23R deficient and wild type mice. The student will then be
involved in assessing the quality of the DNA and preparing the samples for next generation sequencing. Specifically they will learn how to amplify the DNA by
PCR to ligate specific “barcode” and linker extensions allowing samples to be multiplexed and how to prepare library pools to submit for amplicon sequencing.
The student will then learn how to assign the sequences for taxonomic assignment and prepare the data for downstream analysis.
Additionally, the student will set up the experiments of treating mice with antibiotics to determine the differential effect of antibiotics on Il23R deficient mice.
Lastly, the student will learn how to isolate cells from spleen and mesenteric lymph nodes to assess for IL17 production by ELISA. Research technician and a
senior post-doctoral fellow will be responsible for supervising the details of the experimental execution and the teaching of technical skills requires for these
experiments.
Page 19 of 31
SUPERVISOR(S): Marc Jeschke MD, PhD - Professor
TELEPHONE: 416-480-6703
EMAIL: marc.jeschke@sunnybrook.ca
 FIELD OF RESEARCH: Metabolism; Skin Regeneration
 DEPARTMENT: Surgery
PROJECT TITLE: Hypermetabolism and innate immune cells in sever burned patients
PROJECT DESCRIPTION
Severe burn injury is followed by a profound hypermetabolic response that persists up to 24 months after injury. It is characterized by the whole-body
catabolism, elevated resting energy expenditures, hyperglycemia and hyperlipidemia. Long-term exposure to hypermetabolism is linked to dysfunctional
immune system, particularly the innate immune system, which could lead to an increased incidence of infections and sepsis, multi-organ failure and mortality. In
addition, the innate immune cells, such as monocyte and macrophage, also play a role in regulating metabolism. Cytokine products and reactive oxygen species
produced by innate immune cells may have profound effects on burn metabolic response including glucose disposal and utilization in the periphery as well as on
insulin production by the pancreas.
To investigate the detrimental effects of hypermetabolism on innate immune cells and regulatory functions of innate immune system on metabolism or insulin
resistance, we will explore mechanisms by which hypermetabolic processes influence the performance of immune cells and how the immune system might be
targeted as a strategy to treat metabolic problems in burn patients. Specifically, our laboratory is studying 1) mechanisms of cytokine production of macrophage
isolated from patient fat tissue in insulin resistance; and 2) the interactions between hepatocytes and Kupffer cells in response to ER stress or hypermetabolism
in a cell co-culture system; 3) how hyperglycemia and hyperlipidemia influence macrophage differentiation from bone marrow and their functions in an ex vivo
culture system. We believe this approach can further our understanding about the detrimental effects of hypermetabolism in burned patients, and ultimately, shed
some light in identifying novel cellular or molecular candidates we can target to attenuate the hypermetabolic and catabolic responses, thus improving the
survival outcomes of these patients.
The research activities in the lab are not limited to the above-mentioned. We will also examine the functional and phenotypic alternations of the circulating
immune cells in burn patients as well as in many burn animal models. Findings from these animal studies will complement our on-going clinical investigation,
hence strengthening our understanding of the underlying mechanisms that mediate the detrimental pathophysiological changes post-burn. In addition, human
samples of burned skin, fat, muscle and blood obtained with consent from patients will be collected and examined in the research laboratory. Investigations such
as protein blotting, immune cell isolation and staining, gene expressions, immunohistochemistry and Flow cytometry analysis will be conducted.
Our understanding of burn injury and the associated cellular changes will allow us to advance current treatment or design novel therapy for burn patients to
attenuate the damaging clinical effects and improve clinical outcome of the severely burn and critically ill patients.
STUDENT ROLES & RESPONSIBILITIES
At the start, the student will be required to conduct literature research on the topics relevant to the research project. The student will work closely with the members in the
immune-metabolism group and depending on the student’s previous research training, he/she will be supervised by postdoctoral fellow (PDF) in performing tissue culture, tissue
processing, flow cytometry and other molecular techniques. After the student has gained a substantial understanding of the research question and objectives, he/she will be
given a sub-project focusing on a specific molecular pathway and the targets. He/she will work independently (with PDF assistance and guidance) in experimental design and
planning, execution, data collection and analysis. He/she will be required to attend our weekly laboratory progress meeting, as well as bi-weekly meetings with the PDF and the
PI to discuss research progress and challenges. He/she will be required to prepare part of the manuscript writing and data/figure assembly, and poster or oral presentations at the
CREMS research days. At the end of this research project, the student is not only expected to gain scientific knowledge behind burn injury, but more importantly the ability to
conduct wet lab research with minimal assistance.
Page 20 of 31
SUPERVISOR(S): Marc Jeschke MD, PhD - Professor
TELEPHONE: 416-480-6703
EMAIL: marc.jeschke@sunnybrook.ca
 FIELD OF RESEARCH: Metabolism; Skin Regeneration
 DEPARTMENT: Surgery
PROJECT TITLE: Hypermetabolism and innate immune cells in sever burned patients
PROJECT DESCRIPTION
Severe burn injury is followed by a profound hypermetabolic response that persists up to 24 months after injury. It is characterized by the whole-body
catabolism, elevated resting energy expenditures, hyperglycemia and hyperlipidemia. Long-term exposure to hypermetabolism is linked to dysfunctional
immune system, particularly the innate immune system, which could lead to an increased incidence of infections and sepsis, multi-organ failure and mortality. In
addition, the innate immune cells, such as monocyte and macrophage, also play a role in regulating metabolism. Cytokine products and reactive oxygen species
produced by innate immune cells may have profound effects on burn metabolic response including glucose disposal and utilization in the periphery as well as on
insulin production by the pancreas.
To investigate the detrimental effects of hypermetabolism on innate immune cells and regulatory functions of innate immune system on metabolism or insulin
resistance, we will explore mechanisms by which hypermetabolic processes influence the performance of immune cells and how the immune system might be
targeted as a strategy to treat metabolic problems in burn patients. Specifically, our laboratory is studying 1) mechanisms of cytokine production of macrophage
isolated from patient fat tissue in insulin resistance; and 2) the interactions between hepatocytes and Kupffer cells in response to ER stress or hypermetabolism
in a cell co-culture system; 3) how hyperglycemia and hyperlipidemia influence macrophage differentiation from bone marrow and their functions in an ex vivo
culture system. We believe this approach can further our understanding about the detrimental effects of hypermetabolism in burned patients, and ultimately, shed
some light in identifying novel cellular or molecular candidates we can target to attenuate the hypermetabolic and catabolic responses, thus improving the
survival outcomes of these patients.
The research activities in the lab are not limited to the above-mentioned. We will also examine the functional and phenotypic alternations of the circulating
immune cells in burn patients as well as in many burn animal models. Findings from these animal studies will complement our on-going clinical investigation,
hence strengthening our understanding of the underlying mechanisms that mediate the detrimental pathophysiological changes post-burn. In addition, human
samples of burned skin, fat, muscle and blood obtained with consent from patients will be collected and examined in the research laboratory. Investigations such
as protein blotting, immune cell isolation and staining, gene expressions, immunohistochemistry and Flow cytometry analysis will be conducted.
Our understanding of burn injury and the associated cellular changes will allow us to advance current treatment or design novel therapy for burn patients to
attenuate the damaging clinical effects and improve clinical outcome of the severely burn and critically ill patients.
STUDENT ROLES & RESPONSIBILITIES
At the start, the student will be required to conduct literature research on the topics relevant to the research project. The student will work closely with the members in the
immune-metabolism group and depending on the student’s previous research training, he/she will be supervised by postdoctoral fellow (PDF) in performing tissue culture, tissue
processing, flow cytometry and other molecular techniques. After the student has gained a substantial understanding of the research question and objectives, he/she will be
given a sub-project focusing on a specific molecular pathway and the targets. He/she will work independently (with PDF assistance and guidance) in experimental design and
planning, execution, data collection and analysis. He/she will be required to attend our weekly laboratory progress meeting, as well as bi-weekly meetings with the PDF and the
PI to discuss research progress and challenges. He/she will be required to prepare part of the manuscript writing and data/figure assembly, and poster or oral presentations at the
CREMS research days. At the end of this research project, the student is not only expected to gain scientific knowledge behind burn injury, but more importantly the ability to
conduct wet lab research with minimal assistance.
Page 21 of 31
SUPERVISOR(S): Marc Jeschke MD, PhD - Professor
TELEPHONE: 416-480-6703
EMAIL: marc.jeschke@sunnybrook.ca
 FIELD OF RESEARCH: Metabolism; Skin Regeneration
 DEPARTMENT: Surgery
PROJECT TITLE: Toward regeneration of functional skin for burned victims
PROJECT DESCRIPTION
Millions of patients suffer from wounds due to trauma, infections or underlying medical conditions and thus, cutaneous wounds represent a major health care
issue. In condition like burn injury, quick, permanent wound closure is important for patients. Treatment of severe burns includes excision of the wound and
grafting or reconstruction. Inadequate skin for auto-grafting compromises recovery of patients with large burn.
There are few commercially available temporary skin substitute, which has been shown to promote skin healing but it lacks cellular component. Mesenchymal
stem cells (MSCs) isolated from bone marrow elicit promising effect in wound healing. However, the volume of extracted bone marrow and the cell number is
limited, requires 4-6 weeks for culturing and is associated with risks. Allografting of bone marrow derived cells does not have those limitations but it involves
the risks of immunological rejection. The use of human umbilical cord Stem cells with their promising low immunogenicity as universal donor-derived
allogeneic cells could preclude these limitations.
We successfully isolated MSCs from the Wharton-Jelly membrane of human umbilical cords and demonstrated that these cells contain characteristics of MSCs.
Secretome of these cells (WJ-MSCs) promoted skin healing in a mouse skin biopsy wound healing study. We are also optimizing a protocol to isolate epitheliallike cells from same source.
This work is based on expanding on our laboratory’s knowledge on the isolation of different stem cells from human umbilical cords and translating this through
incorporation of stem cells into the potential hydrogels dressing to promote skin regeneration.
Our unique approach promises the rapid and low cost formation of skin substitute that are populated with non-immunogenic umbilical cells and with properties
that closely match the pathophysiological features of human skin. Bi-layered skin substitute will be developed at throughputs that are ultimately clinically
relevant for the treatment of severe burns and characterized in vitro and in vivo.
STUDENT ROLES & RESPONSIBILITIES
Student will evaluate two potential hydrogel and will incorporate our isolated/ well characterised stem cells into the hydrogels. Student will characterise the
newly bio-fabricated skin in vitro using different tissue staining methods. She/He will further characterise the bilayer skin substitute using Scanning Electron
Microscopy (SEM), Mercury Porosimetry and micro Computed tomography (μCT). These will provide information regarding the scaffold porosity and
architecture with and without cells.
With help of our associate scientists, the bio-fabricated skin substitute will be grafted into the mouse skin burn model. To evaluate the functionality of newly
formed skin, the student will evaluate regenerated skin for: Tensile stress-strain, their elastic modulus, extent of keratinisation, extent of collagen deposition, the
fate of seeded human SCs and the distribution of melanocytes. The potential student will be trained accordingly.
Page 22 of 31
SUPERVISOR(S): Michael Cusimano MD, PhD - Professor
TELEPHONE: 416-864-5312
EMAIL: injuryprevention@smh.ca
 FIELD OF RESEARCH: Trauma; Tumor
 DEPARTMENT: Surgery
PROJECT TITLE: Understanding the risk factors and behavioural and cognitive outcomes associated with
Traumatic Brain Injury
PROJECT DESCRIPTION
This study examines the link between vulnerability, violence, risk taking behaviors and traumatic brain injuries. It also explores the outcomes of
traumatic brain injury related to cognition, brain structure, and behavior. The hypothesis is that vulnerable populations are more susceptible to
experiencing incidences of traumatic brain injuries, many of which are caused by modifiable risk factors. These vulnerable groups include patients
of the hospital who’ve sustained traumatic brain injury as a result of motor vehicle accidents, falls, wards of the state, homeless individuals, or
involved persons charged with assault in domestic violence. The study aims to answer how social and community markers (e.g. SES, ethnicity,
education), cause of injury (e.g. MVC vs. assault), and degree of injury manifest themselves in a patient.
STUDENT ROLES & RESPONSIBILITIES
The student has the option of being involved in a number of aspects of the STAIR project. The specific project depends on the student’s abilities
and interests. Opportunities exist for the analysis of MRI imaging - e.g. doing DTI studies; qualitative analysis of interview data; qualitative
analysis of neuropsychological and questionnaire data or larger population databases; studies of sports concussion in youth; performing systematic
reviews in combination with one of the aforementioned studies, or, designing a study related to the goals of the project. The opportunity also
exists to work on a project within the saccades and TBI project or the Teen TBI project, or one of the many projects in clinical
neurosurgery. Opportunities exist for clinical experience as well in neurosurgery.
Students will be expected to become active participants in ALL aspects of the study up to and including manuscript preparation, KT activities and
supervision of more junior students.
Page 23 of 31
SUPERVISOR(S): Michael Fehlings MD, PhD, FRCSC, FACS - Professor
TELEPHONE: 416-603-5627
EMAIL: michael.fehlings@uhn.ca
 FIELD OF RESEARCH: Spinal Cord Injury; Regenerative Neuroscience
 DEPARTMENT: Genetics & Development
PROJECT TITLE: Neural stem cell repair and regeneration of the injured spinal cord
PROJECT DESCRIPTION
In recent work supported by CIHR, we demonstrated that transplanted neural precursor cells (NPCs) promote recovery after thoracic spinal cord injury (SCI)
which is associated with remyelination of spared axons. We further reported, in studies of shiverer mice which lack myelin basic protein (MBP), that
transplanted NPCs induce remyelination with restoration of a normal molecular organization of the nodes of Ranvier and improved neurophysiological function.
Moreover, a combinatorial approach using NPCs and chondroitinase ABC (ChABC) to reduce glial scarring was successful in promoting functional
neurobehavioral recovery and anatomical plasticity following chronic SCI. These data suggest that NPCs could be an attractive strategy to repair the injured
cord. However, the clinical translation of NPCs and other stem cell technologies for SCI is currently hindered by several key issues: a) lack of studies in
clinically relevant cervical compressive/contusive SCI models; b) limitations posed by the hostile post-traumatic environment including glial scarring, cystic
cavitation and ongoing secondary injury processes which limit survival of transplanted cells; and d) continued uncertainty regarding the mechanisms of action of
NPCs—in particular related to the relative contributions of remyelination and enhanced plasticity.
Hypotheses: To address these key issues, we plan to undertake experiments in a novel, clinically relevant cervical model of compressive/contusive SCI to
examine the following hypotheses: a) remyelination of injured axons by NPCs is a key mechanism by which they mediate functional recovery after SCI; b)
approaches to reduce glial scarring by transfection with ChABC or injection with self-assembling nanofibrils (SAPs) will enhance the survival, integration and
distribution of NPCs and induce functionally relevant plasticity; and c) combinatorial therapy with sodium channel blocker Riluzole (currently in Phase I clinical
trials for SCI in humans) will further enhance survival and integration of NPCs following SCI with improved neurobehavioral outcomes.
Experimental approach: Experiments will use a novel cervical model of compressive/contusive SCI in rodents. Either wild type or MBP-deficient shiverer (to
examine the relative impact of induction of myelination) murine NPCs or NPCs derived from induced pluripotent stem cells (iPSCs) will be transplanted.
Outcomes will include neurobehavioral assessments (IBB; grid walk; Catwalk; forelimb assessments; respiration; neuropathic pain), in vivoand ex vivo
electrophysiology and neuroanatomical assessments (confocal immunohistochemistry, immunogold EM; axonal tracing; quantitative lesion assessment;
stereology-based cell counts).
Impact/significance: Our findings have the potential for real impact to facilitate the translation of stem cell therapies from bench to bedside for patients with
SCI and other neural injuries.
STUDENT ROLES & RESPONSIBILITIES
The student will learn about models of spinal cord injury, microsurgical implantation of neural stem cells and neuroanatomical, neurophysiological and neurobehavioural
assessments. The student will work collaboratively in a multidisciplinary research team on all facets of the project.
There is excellent technical assistance in the laboratory and ready interaction with a wonderful team of experienced neuroscientists and students at various levels of training.
The CREMS student will have the opportunity to analyze, criticize, and present current literature reviews as a part of our laboratory’s monthly journal club. By the end of the
research term, the CREMS student will have gained valuable research experience in the field of SCI through exposure to a variety of essentials research techniques and methods
in molecular biology, behavioral study and microsurgery.
Page 24 of 31
SUPERVISOR(S): Paul Dorian
TELEPHONE: 416-864-5104
EMAIL: dorianp@smh.ca
 FIELD OF RESEARCH: Arrhythmias; Cardiology
 DEPARTMENT: Pharmacology
PROJECT TITLE: Exercise Frequency and Fibrillation Outcomes: Remodeling and Tachycardia
PROJECT DESCRIPTION
BACKGROUND: Regular exercise reduces cardiovascular (CV) morbidity and all-cause mortality. However, there is growing evidence that ‘excessive’
endurance exercise increases the risk of adverse cardiac health outcomes including transient cardiac dysfunction, myocardial damage, and
arrhythmias.There is compelling evidence that ‘excessive exercise’ may produce a phenotype that is pro-arrhythmic, potentially affecting thousands of
middle-aged endurance exercise participants. There is a knowledge-gap about the physiology of excessive exercise on the heart, particularly hemodynamic
and systemic alterations that occur during acute and chronic exercise leading to cardiac remodeling. Our research plan is to further understand the interplay
between an individual's phenotype and the heart's response to intensive exercise in an aging cohort who have participated long-standing exercise. We will
examine the cardiac consequences of vigorous exercise in those with a long history of excessive exercise compared to age-matched individuals who
perform moderate exercise at recommended ‘cardio-protective’ levels.
HYPOTHESES: 1) Long-term excessive exercise induces atrial and right heart remodeling compared to age-matched, moderate exercising controls, along
with disproportionate elevations in right ventricular and pulmonary pressures during acute and prolonged exercise, compared to moderate-exercise controls;
These alterations will be correlated to atrial size and life-time training hours; 2) left atrial and right ventricle dilatation and dysfunction occurs during
prolonged exercise in excessive, but not moderate exercisers with presence of inflammation, enhanced vagal tone ECG abnormalities during recovery from
prolonged exercise.
METHODS: We will screen 200-300 such life long endurance athletes with a clinical and exercise history and ECG and assess potential risk for arrhythmias
and abnormal cardiac structure .
A subset will undergo Protocol 1 , which will fully characterize their phenotype by maximal exercise testing, exercise history, resting cardiac MRI,
biomarkers for inflammation, and signal-averaged P-wave dispersion and 48 hr. Holter ECG. Subjects will include 40-65 year old endurance athletes (EA,
n=30) and moderately active age-matched controls (RA, n=30). Protocol 2 will be an exercise intervention study with a 24-hour follow-up assessment. The
exercise study will include a peripherally accessed right ventricular (RV) catheterization to monitor real-time cardiac hemodynamics and pulmonary (and RV)
pressures, concurrent with echocardiography (ventricular and atrial function) at rest, after 20 min. and 45 min. of exercise (both groups) and following 90 min.
of exercise (EA only) at 80% VO2max. These data will be related to atrial size, and lifetime hours of exercise. Post-exercise biomarkers of inflammation,
cardiac stress and 24-hour Holter (heart rate variability, presence of atrial/ventricular ectopy) will also be obtained with echocardiography and biomarkers
assessed 24-hours after exercise. Primary outcomes are atrial size at rest (cMRI), pulmonary artery systolic pressure, and atrial and right ventricular function
during exercise. Secondary markers include increased signal-averaged P-wave duration and atrial ectopy and markers of inflammation in recovery. We expect
to see presence cardiac remodeling in the EA group (atrial and RV size, elevated RV and pulmonary pressures and PCWP during exercise), with evidence of
post-exercise RV and atrial fatigue, inflammation, increased vagal-modulated heart rate variability after prolonged exercise (90 min.) in the EA group.
Page 25 of 31
IMPORTANCE: This study will provide novel information on the factors that may increase vulnerability to exercise-induced adverse cardiac remodeling.
Moreover, our protocols will allow for an examination of the interplay between phenotype and the physiological stress of exercise, clarifying both the limits
of appropriate exercise, and the normal boundaries of the cardiac responses during clinical exercise stress assessments.
STUDENT ROLES & RESPONSIBILITIES

To be actively involved in participant recruitment, data collection, ECG analysis (including the evaluation of athletic participants with abnormal ECG
findings), and medical history verification.

To assist with literature review, establishing distribution of exercise load over time, organizing the non invasive tests and data recording and analysis ;
grant, abstract, and manuscript writing.

To collaborate directly with clinicians, research scientists, postdoctoral fellows, and graduate students with other aspects of the project.
Page 26 of 31
SUPERVISOR(S): Paul Dorian
TELEPHONE: 416-864-5104
EMAIL: dorianp@smh.ca
 FIELD OF RESEARCH: Arrhythmias; Cardiology
 DEPARTMENT: Pharmacology
PROJECT TITLE: The Family Study: Assessment of the incidence, etiology and familial risk for sudden cardiac
arrest in young individuals and their family members
PROJECT DESCRIPTION
Background: Sudden cardiac arrest (SCA) in young individuals is a devastating occurrence for the victim’s family, friends, and community. It is usually defined as a natural
event with cardio-respiratory collapse which occurs suddenly, unexpectedly and of cardiac cause1. Recent reviews have highlighted our lack of information on the incidence and
etiology of SCA in the young (called “young SCA”), particularly with regard to the potentially preventable triggers of exercise/sport, and identifiable familial predisposition to
fatal arrhythmias11.
Study Rationale: Uncertainty over the best approach to preventing young SCA is largely due to a lack of data regarding the true incidence and etiology of young SCA,
particularly with regard to the potentially preventable triggers and identifiable familial predisposition. The current proposal will address limitations of prior studies by using a
validated comprehensive population based registry of consecutive cases to identify patients, precise case definitions, inclusive young SCA patient populations, and
comprehensive data collection methods.
General Objective: To understand the incidence, etiology and familial pattern of Sudden Cardiac Arrest (SCA) in the young.
Specific Objectives:
i. Incidence and Etiology: To measure the incidence rate and etiology of SCAs that occurs in individuals ages 2-45 years within the Greater Toronto Area over the 5 year
period 2009-2013.
ii. Triggers and Circumstances: To assess the environmental triggers (e.g. physical exercise) and circumstances (e.g. warning signs or symptoms) of young SCA within this
population.
iii. Familial Inheritance: To evaluate the familial risk pattern for SCA and young SCA in family members. Specifically, we will measure the frequency of SCA and young
SCA in first-degree family members among young SCA individuals compared to relevant control populations.
Significance:
This project will further the understanding of the scope and nature of SCA in the young. Accurate data regarding SCA are required to create recommendations or guidelines
regarding prevention and referral of families for further care.
STUDENT ROLES & RESPONSIBILITIES
 To assist with pt screening from the registry of all out-of-hospital cardiac arrests in the city of Toronto for cases that meet the inclusion criteria;
 To assist with the adjudication of the underlying etiology for each eligible case by viewing all available information including EMS reports, inhospital
data, coroner investigative statements, autopsy, toxicology and post mortem reports.
 To consent and conduct interviews with controls, cases, and their first-degree relatives.
 To recruiting controls from the Family Practice Units and daily list of scheduled PCI procedures at St. Michael’s Hospital.
 To collect data, analyze and enter data into a database.
 To assist with literature reviews, grant, abstract and manuscript writing.
Page 27 of 31
SUPERVISOR(S): R. Loch Macdonald
TELEPHONE: 416-864-5452
EMAIL: macdonald@smh.ca
 FIELD OF RESEARCH: Brain; Vascular
 DEPARTMENT: Neurosurgery
PROJECT TITLE: Pathogenesis of Brain Injury after Subarachnoid Hemorrhage
PROJECT DESCRIPTION
The goals of our laboratory are to define the cellular and molecular mechanisms that cause angiographic vasospasm, microvascular injury and poor outcome
after subarachnoid hemorrhage. The approach is translational and uses techniques ranging from animal surgery, molecular biology (PCR, Western blotting),
immunohistochemistry to confocal imaging, microscopy and electrophysiology and focuses on mechanisms of brain injury after subarachnoid hemorrhage. We
are studying how blood clot contracts cerebral arteries and how to prevent it. We used rodent, dog and nonhuman primate models of SAH and vasospasm, and
found that voltage gated calcium channels and endothelin-mediated signaling, possibly involving TRP proteins, are important. The role of inflammatory
cytokines such as tumor necrosis factor are also being studied in mouse models. We also study ion channels in vascular smooth muscle with and without
vasospasm and how altering expression of ion channels to determine effects on vasospasm and vascular remodeling. Second, we conduct extensive clinical work
with patients where we are investigating mechanisms of poor outcome after SAH. Patients who survive after SAH often have neurocognitive deficits. The
etiology of these deficits is unknown and may involve processes other than vasospasm. We developed anterior circulation SAH models in rats and mice,
characterized neurobehavioral deficits in these animals and are examining mechanisms of dysfunction by electrophysiologic study of hippocampal function and
molecular analysis of the brain.
STUDENT ROLES & RESPONSIBILITIES
The Student is expected to learn the laboratory methods involved in the laboratory or clinical studies, such as imuunohistochemistry, Western blotting,
electrophysiology or clinically all of the details of subarachnoid hemorrhage, clinical epidemiology and statistics. In the laboratory or clinical research, the
student must learn scientific study design, statistics and writing of a research manuscript, presenting research results at local academic meetings and national or
international conferences.
Page 28 of 31
SUPERVISOR(S): Thomas K. Waddell
TELEPHONE: 416-581-7502
EMAIL: tom.waddell@uhn.ca
 FIELD OF RESEARCH: Lung; Regenerative Medicine
 DEPARTMENT: Thoracic Surgery
PROJECT TITLE: Recellularization of lung scaffolds using respiratory progentior cells
PROJECT DESCRIPTION
Transplantation remains the only truly curative intervention for end-stage lung diseases. However, like all other transplanted organs, there is a serious and
chronic shortage in donated lungs. It is therefore imperative to develop novel therapies for chronic degenerative conditions. Regeneration of healthy lungs is an
exciting long-term goal but successfully reproducing the complex architecture of the lung presents a formidable challenge. We propose to produce the necessary
epithelial cellular components for lung regeneration, taking into consideration the requirement of (1) appropriate cell populations and specific cellular
phenotypes; (2) controlled proliferation and differentiation; (3) scale-up and process optimization; and (4) therapeutic validation. Of particular interest is
research is the application of stem cells or progenitor cells in lung tissue engineering approaches such as scaffold repopulation. Existing studies in this field have
focused on the use of exogenous stem cells such as embryonic stem (ES) cells or bone marrow derived mesenchymal stromal cells (MSC) for decellularized lung
scaffold cell repopulation. We hypothesize that the use of cells originating from the lung itself, may offer an advantage resulting in enhanced cell survival and
differentiation. We have applied a novel approach using advanced molecular controls, whereby we used controlled, transient exogenous activation of
Yamanaka’s four transcription factors, which reprogram to induced pluripotent stem (iPS) cells but turned them off prior to reaching the commitment point
leading to pluripotency. Since the resulted cells behaved as “progenitors” in that they undergo controlled proliferation and differentiation into a limited range of
progeny, we call these cells “induced Progenitor Population (iPP) cells” and propose that they represent an excellent choice to advance the field through
recellularization of decellularized lung scaffolds. The objectives of this study will focus on generating sufficient iPP from 3 distinct airway epithelial cell types
(Clara, alveolar type II (AEC-II), and basal) cells through optimized transient reprogramming; and to test whether these iPP cells will re-populate decellularized
lung scaffolds.
STUDENT ROLES & RESPONSIBILITIES
The student will be involved in one of two sub-studies pertaining to the above described project:
(1) To generate iPP cells from alveolar type II cells (AECII) and basal cells



Specific Aim I – To isolated AECII and basal cells from available and established ROSA26-rtTA an Col1a1::tetO-4F2A transgenic mice
which allows for the induction of the Yamanaka reprogramming factors (Oct4, Sox2, Klf4, cMyc) under the control of doxycycline.
Specific Aim II – Find the appropriate dose and duration for doxycycline treatment, resulting in enhanced proliferation but not reaching the
(induced pluripotent) iPS state.
Specific Aim III – Generate and characterize AECII and basal cell derived iPP cells using established protocols in the lab.
Student will learn/improve upon cell culture techniques, handling of mice, tissue isolation, molecular biology, immunostaining and fluorescence imaging.
(2) To re-populate decellularized lung scaffolds using iPP cells generated from Clara, AECII and basal cells
 Specific Aim I – To decellularize and characterize lung scaffolds isolated from mice using established techniques in the lab.
 Specific Aim II – To re-populate decellularized lung scaffolds with epithelial iPP cells while using bone marrow derived cells as a control.
 Specific Aim III – To determine if cells survive, proliferate and differentiate on decellularized lung scaffolds using established protocols in
the lab.
Student will learn/improve upon cell culture techniques, handling of mice, decellularization of whole lung scaffolds, molecular biology, immunostaining
and fluorescence imaging.
Page 29 of 31
SUPERVISOR(S): Robert Wu
TELEPHONE: 416-340-4567
EMAIL: robert.wu@uhn.ca
 FIELD OF RESEARCH: Medical Informatics; Communication
 DEPARTMENT: Medicine
PROJECT TITLE: Improving the discharge process with a Discharge App
PROJECT DESCRIPTION
The discharge process is a transition of care for the patient from an acute care hospital usually to home. This transition of care can cause challenges which include adverse events
as well as unplanned readmissions. Communication around the discharge process has been found to be poor. The discharge summary is the primary mode of communication
between the hospital care team and the aftercare providers. Important elements of the discharge summary include: the outcome of the hospitalization, disposition of the patient,
medications at discharge, and follow up care. Unfortunately, patient understanding of key elements of post-discharge care is poor. Improving the communication of discharge
could improve care.
Methods
Research question
Will a patient-centered discharge application improve the care of patients?
Intervention
We will design and create a patient-centered smartphone application that will have useful information from the discharge summary: patient issues, medications, and follow up.
Patients will be able to download the app from an App Store. If patients consent to the study, they will receive an electronic version of the discharge summary by email which
can be uploaded to the Discharge App. From this app, patients or their caregivers will be able to view the reason they were admitted, their medication list at discharge, and their
follow up instructions.
Usage of the app will be logged.
Standard care
A paper discharge summary.
Study design
Pilot study of 20 patients – to determine whether patients and their caregivers will use the application, how they will use it.
Patient recruitment
For patients being discharged from General Internal Medicine at University Health Network, we will ask them if they would like to have their Discharge Summary electronically
as well as on paper.
Inclusion Criteria:

Patients being discharged from General Internal Medicine

The patient or their substitute decision maker is able to consent to participate and they understand the risks to the Personal Health Information

Patient or caregiver has a smartphone (iphone or android)
Data collection
We will keep a log of all patients approached and reason for not participating (no consent, no smartphone). For those patients enrolled, we will call them 2 weeks after discharge
to check on whether they are using the application, whether they have any issues, and whether they have any suggestions for improvements.
STUDENT ROLES & RESPONSIBILITIES
The student’s roles and responsibilities will be to lead this project using the resources of the research team to support the project. These responsibilities will include literature
reviews, designing the intervention, working with the development team to create the application, then refining and eventually piloting with patients. Responsibilities will then
include recruitment of patients and data collection for a pilot group. Finally, responsibilities will include analysis and write up of a manuscript of the pilot study.
While Ethics has not yet been obtained, we expect it to be obtained by January 2014.
Page 30 of 31
SUPERVISOR(S): Stephen Fremes
TELEPHONE: 416-480-6100 ext. 6073
EMAIL: stephen.fremes@sunnybrook.ca
 FIELD OF RESEARCH: Cardiovascular; Diseases
 DEPARTMENT: Surgery
PROJECT TITLE: Mid-term Follow of Patient Prosthesis Mismatch: A comparison between surgically implanted
Bioprostheses and TAVI
PROJECT DESCRIPTION
The concept of prosthesis-patient mismatch (PPM) was first introduced by Rahimtoola, and it can occur when the effective orifice area (EOA) of an aortic valve
prosthesis is considered to be too small in relation to a patient’s body after aortic valve replacement (AVR) [1]. PPM reflects residual aortic stenosis, and
consequently, may lead to incomplete left ventricular mass regression and possibly decrease survival after AVR.
Recently, stent valves have been manufactured to allow the procedure to be performed using a catheter rather than open surgery (TAVI). The stent valve uses
leaflets from an animal (similar to a bioprosthesis) which are mounted on a collapsible stent. The stents are either balloon expandable or self-expanding. The
crimped valve is positioned in the diseased native aortic valve, via a catheter approach and then delivered. The stent valve once delivered does not migrate as the
stent is sufficient to secure the position of the valve within the native annulus. This treatment has been performed in elderly patients who are considered either
inoperable [4, 6] or at very high risk of open surgery [5, 6]. The procedure has been performed at Sunnybrook for almost 4 years.
The transcatheter valves are hemodynamically very efficient, as the valves are usually oversized for the annulus (to minimize leakage around the valve), and as
the stent used to support the leaflets is very thin, unlike the semi-rigid stent used for surgically implanted valves. However, leakage around the valves is much
more common, as the diseased aortic valves with associated calcified deposits are not removed preventing a perfect seal. Aortic regurgitation following TAVI is
associated with worse outcomes. The objective of this study is to compare the mid-term outcomes between surgical AVR and TAVI.
We hypothesize that: 1) the incidence of PPM following TAVI will be similar or less than following surgical AVR and 2) periprosthetic AI will be associated
with incomplete left ventricular mass regression following TAVI.
TAVI patients are routinely followed in the TAVI clinic and have routine surveillance echocardiography. The first TAVI was performed at Sunnybrook in
September 2009. The Cardiac Surgical Database will be queried for patients that underwent tissue AVR from January 2010 until the present. Patients with
concomitant CABG are included (as TAVI patients frequently have pre-procedural PCI). Patients undergoing redo AVR are also included. Patients who had
surgical AVR for active endocarditis or with predominant AI rather than AS or AS/AI will be excluded. Patients who have not been actively followed at
Sunnybrook following surgical AVR will have telephone follow-up for clinical status and return to Sunnybrook for transthoracic echocardiography. For patients
who have been actively followed at Sunnybrook following surgical AVR, we will obtain data from the clinic notes and follow-up echocardiography. We will
compare the preoperative echocardiogram data with the postoperative one and the latest one.
STUDENT ROLES & RESPONSIBILITIES




Literature Search
REB submission / renewals
Patient Follow-up
Data entry




Assist in Grant Proposals
Presentation
Basic Statistics
Electronic Data Entry
Page 31 of 31
SUPERVISOR(S): Andrea Kassner
TELEPHONE: 416-978-4623
EMAIL: andrea.kassner@utoronto.ca
 FIELD OF RESEARCH: Neuroimaging; cerebrovascular and CNS disorders
 DEPARTMENT: Medical Imaging
PROJECT TITLE: Prediction of MS relapse using advanced MRI
PROJECT DESCRIPTION
Lab Overview
My research is focused on advanced neuroimaging methods to investigate neurologic diseases. There are programs in ischemic stroke, sickle cell disease, sleep
apnea, and multiple sclerosis. Advanced imaging methods are used to predict the course and assess the treatment of these diseases. Animal models and clinical
studies are used to conduct these investigations.
Details of CREMS Project
Progression of multiple sclerosis (MS) results in subtle alterations of the neurovascular unit, which can be detected by advanced MRI techniques such as DCE
MRI and subsequent pharmacokinetic analyses. Evidence suggests that progression and relapse of MS may be predicted by application of these MRI techniques.
Currently, advanced imaging plays a limited role in clinical MS diagnosis and management. This project will invesitgate the potential of these advanced MRI
techniques pre- and post treatment in an MS animal rat model.
STUDENT ROLES & RESPONSIBILITIES
The CREMS student will work with a rodent model of Multiple Sclerosis (the experimental autoimmune encephalitis model). The student will investigate and
compare a variety of MRI measures in this model to assess the ability to predict relapse, neurocognitive decline, and response to treatment. The measures
assessed will include but may not be limited to permeability imaging, diffusion tensor imaging, and magnetisation transfer imaging. The student will also
conduct histological exams on rat brain tissue.
Desirable skills
-
Fast and independent learner.
Research experience especially in a wet lab or imaging lab will be an asset.
Good computing skills and basic knowledge in statistics.
Experience with animal models (especially MS models) is an asset but not required.
Self-direction and an ambition to attain high levels of productivity.