Comprehensive Research Experience for Medical Students 2016

Comprehensive Research Experience for Medical Students
2016 Research Scholar Program
Available Projects
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 [email protected] by end of day November 24, 2015.
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!
SUPERVISOR: R. Loch MacDonald MD, PhD
EMAIL: [email protected]
 FIELD OF RESEARCH: Neurosurgery / Stroke
PROJECT TITLE: Pathophysiology of Subarachnoid Hemorrhage
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. Using variety animal models, we found that voltage gated
calcium channels and endothelin-mediated signaling, possibly involving TRP proteins, are important. The role of inflammatory
cytokines such as TNFa is also being studied in mouse models. We also study role of ion channels in mediating vasospasm and
vascular remodeling. 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 expected to learn the laboratory methods involved in the laboratory, such as immunohistochemistry, Western blotting,
electrophysiology etc.
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.
Student will be supervised by the PI and the Research Associate in the laboratory
SUPERVISOR: Jennifer Jones, PhD
EMAIL: [email protected]
 FIELD OF RESEARCH: Cancer Survivorship, implementation research, health services
PROJECT TITLE: Eliminating Digestive Irregularities caused by Late Effects (EDIBLE) of abdominopelvic radiation: A pilot
study of culinary and nutrition intervention
Patients diagnosed with gynecological (GYN) are commonly treated with radiation therapy to the pelvic area. Exposing the
pelvic area to radiation therapy can often cause long-term gastrointestinal (GI) side effects which may include fecal incontinence,
flatulence, bloating and rectal bleeding. The management of GI symptoms resulting from radiation therapy includes increasing
soluble fibre and limiting insoluble fibre, fat and lactose. Providing self-management support to GYN patients who suffer from
GI symptoms after radiation therapy may be an effective strategy to help them improve their QoL. This pilot study will evaluate a
newly developed innovative nutrition and culinary education intervention for GYN cancer patients (EDIBLE). The research
objectives are to: 1) assess the feasibility and acceptability of the methods and the intervention; and 2) a preliminary estimate on
the efficacy of the intervention on bowel symptoms, QoL, knowledge and food intake. Forty post-treatment cancer survivors will
be recruited from GYN cancer clinics at the Princess Margaret Cancer Centre, University Health Network (UHN). Patients who
provide informed consent to participate will complete baseline measures (T1) to assess bowel symptoms (primary outcome),
quality of life, and nutrition knowledge and dietary intake (secondary outcomes). The intervention (EDIBLE) includes 2x 2 hour
nutrition and culinary education workshops led by a registered dietitian (RD) and culinary chef with 6 weeks of email
reinforcement and support. EDIBLE will be delivered in the teaching kitchen at ELLICSR (, a research facility
for predicting, preventing and managing long-term adverse effects of cancer and its treatments and part of the Princess Margaret
Cancer Rehabilitation and Survivorship Program. Measures will be repeated at 6 weeks (T2) and 3 months (T3) postintervention. The results of this pilot study will be used to inform the development of a larger randomized control trial.
Student will work closely with Drs. Jones and Ferguson and the research and clinical tem at ELLICSR ( and the Gyne
site team.
Involved in all aspects of the study from start to finish, including patient recruitment and screening, quantitative and qualitative
evaluation, analyses and dissemination of study findings (presentations & publication).
During the summer, the student will take part in the ELLICSR Summer Student Program which includes a series of seminars and
presentations to introduce students to cancer survivorship and research
SUPERVISOR: Corrine Fischer MD
EMAIL: [email protected]
 FIELD OF RESEARCH: Neurodegenerative Disorders
PROJECT TITLE: Prevalence of serum NMDAR autoantibodies in first-episode psychosis
Anti-N-methyl-D aspartate receptor (NMDAR) encephalitis is an inflammatory condition of the brain discovered in 2007 by Dalmau and
colleagues where antibodies are formed against the NMDAR receptor of the brain. It may also be associated with benign germ cell tumours
called “teratomas”, which may, in some instances, develop central nervous system tissue that expresses the NMDAR receptor, thus
triggering the development of antibodies that cross the blood brain barrier and attack the brain. The condition is often associated with a
psychiatric presentation, specifically first episode psychosis (FEP), as well as cognitive decline. As a result, there is potential for
misdiagnosis as patients are often referred initially to psychiatrists, who may be unaware of the diagnosis. This may have significant
treatment implications for the patients not identified, as there is significant potential for improvement and even remission if patients are
identified and treated at first presentation with immunotherapy. Patients who are not identified and in whom treatment is therefore delayed
or withheld may suffer a number of adverse consequences, including the development of chronic psychotic symptoms, significant cognitive
decline and in some instances death. Moreover, the disorder is easily detected in the serum and cerebrospinal fluid of patients.
Unfortunately, the scope of this problem is not clear as psychiatrists do not routinely screen for this condition in patients presenting with
FEP, in spite of the potential for recovery. It is estimated that as many as 10% of patients with chronic psychotic illnesses may in fact have
anti-NMDAR encephalitis based on retrospective analyses of blood samples. However, well designed prospective studies are lacking. The
purpose of our study is to screen patients presenting to an acute care hospital with FEP for anti-NMDAR encephalitis to identify the
prevalence of this condition. We will examine the demographic and clinical correlates of positive status, including age, gender, profile and
severity of psychotic symptoms as well as cognitive deficits, in order to better define the at risk population, both cross-sectionally and
longitudinally, in a matched sample of subjects . As well, we will gather detailed information on the first episode. In addition, we will
examine imaging correlates of positively identified patients relative to patients who test negative, including grey matter volume, white
matter changes and network connectivity, both cross-sectionally and longitudinally over time in a matched sample of patients. It is our hope
that the findings from our study will establish how common this disorder is among FEP patients and thus whether or not it merits routine
screening. In addition, we will follow patients positively identified over time and compare imaging and clinical findings pre and post
treatment to clarify the neurological mechanisms leading to psychotic symptoms in this disorder. This will provide important insights into
the underlying mechanism of psychosis in other disorders, potentially leading to novel treatment approaches.
Student to be involved in all aspects of the study.
Responsible for assisting with recruitment of subjects, consenting potential subjects, assessing potential subjects, collecting data and
organizing imaging studies of patients
Responsible for conducting analyses of clinical and imaging data of patients at baseline and over time.
Responsible for presenting the data at a scientific conference in the form of a poster or oral presentation.
Will be responsible for writing up results of the study for a scientific publication
PI will serve as the student’s direct supervisor with additional supervision provided by the graduate student and the assigned research
SUPERVISOR: Anish Kirpalani
EMAIL: [email protected]
 FIELD OF RESEARCH: Abdominal MRI / Fibrosis
PROJECT TITLE: Noninvasive Magnetic resonance Elastography as a Prognostic Biomarker for Outcomes in Kidney
Transplantation Patients with Chronic Kidney Dysfunction
Kidney transplantation (KT) has revolutionized the care of patients with kidney failure, a disease characterized by high morbidity
and mortality. Unfortunately, while short-term transplant outcomes have dramatically improved over the last 30 years, long-term
(>1 year) outcomes have improved only marginally. A major reason for this persistent late graft loss is the development of
chronic allograft injury (CAI), the incidence of which is estimated to be 60% at 10 years post-KT. Of all patients biopsied > 1 yr
post-KT for CAI, roughly one third will develop graft loss at a median of 14 months post-biopsy. One common and ominous type
of CAI is fibrosis, a process that is progressive, irreversible, and predictive of poor outcomes. Accordingly, accurate
quantification of whole allograft fibrotic burden would provide critical prognostic information and guide therapeutic decisions.
Unfortunately, current non-invasive tests fail to accurately measure allograft fibrosis. Instead, the current reference standard for
fibrosis assessment is allograft biopsy, an invasive procedure that samples <1% of the kidney. As biopsy is limited by the risk of
adverse events and sampling bias, new non-invasive measures of whole organ fibrosis burden would thus be a major and highly
clinically relevant advance.
Magnetic resonance elastography (MRE) is a non-contrast, non-invasive imaging test that via measuring organ stiffness, can
estimate fibrotic burden. While MRE has been shown to accurately measure liver fibrosis, whether MRE can quantify fibrosis of
the transplant kidney, a more heterogeneous organ, has not been well studied. Given that fibrosis is a predictor of future graft
dysfunction, the use of MRE to noninvasively measure fibrosis on a kidney-wide scale may offer significant prognostic and
therapeutic benefits.
We are performing a single centre, prospective cohort study to examine the value of MRE as a non-invasive prognostic
biomarker for renal allograft outcomes. We are doing this by recruiting KT patients who present for a clinically indicated biopsy
because of suspicion for chronic renal allograft dysfunction > 1 yr post-KT. In these patients, we are performing both biopsy and
MRE and follow them with regular clinic visits for a minimum of 1 year. We will measure eGFR at regular intervals and monitor
for the occurrence of a clinically significant renal event (SRE).Our objectives are to estimate and compare the accuracy of mean
MRE-derived stiffness in predicting a clinically significant renal event (SRE) and in predicting the rate of decline in estimated
glomerular filtration rate (eGFR) over 1 year in patients > 1 year post-KT in need of a clinically indicated biopsy.
This study has received institutional REB approval. The student will work with the primary supervisor in Medical Imaging along
with a collaborative team including a transplant nephrologist and a faculty MRI physicist at St. Michael's Hospital.
Data collection
Data Analysis and Statistical Analysis
Literature Review
Scientific Writing of Abstract and Manuscript
SUPERVISOR: John Kingdom
EMAIL: [email protected]
 FIELD OF RESEARCH: Placental Basis of Severe Pre-eclampsia and Intra-uterine Growth Restriction
PROJECT TITLE: Placental Response to Heparin: In-Vivo and In-Vitro Studies to Prevent Severe Pre-eclampsia
T Severe pre-eclampsia is a placenta mediated disorder characterized by hypertension, vascular injury and multi-organ dysfunction in the 3rd
trimester. The disease becomes established during the 2 nd trimester, and presents in the 3rd trimester as hypertension and systemic illness, often
with intra-uterine growth restriction of the fetus. Normal pregnancy is characterized by early and progressive increases in cardiac output and
blood volume; these changes are accompanied by a substantial fall in systemic vascular resistance, hence blood pressure falls during the 2nd
trimester. Our in-vivo studies in the 2nd trimester of high-risk women with sonographic and biochemical evidence of placental dysfunction
shows that they have dramatically different hemodynamics, characterized by low cardiac output and very high systemic vascular resistance,
which over 4-6 weeks evolves into overt hypertension. The anticoagulant drug heparin appears, from systematic reviews of several smaller
randomized trials, appears to reduce the recurrence risk by as much as 50%. The mechanism is presently unknown but is likely independent of
it’s anticoagulant actions. Our lab is focused on this subject to determine the non-anticoagulant actions of heparin that may prevent this
disease. We have exclusive access to a patented truncated heparin for our studies in trophoblast cells, human villous explants and the rat
model (surgically-reduced uterine perfusion) of pre-eclampsia. In tandem we study cardiovascular hemodynamics in healthy low-risk and
high-risk pregnant women at Mount Sinai Hospital, via our Placenta Clinic and in collaboration with the Cardiovascular Research laboratory
(including In-Vivo responses to heparin in high-risk subjects). Explanted placental villi from severe pre-eclamptic women condition media to
be strongly anti-angiogenic; these villi secrete less pro-angiogenic placenta growth factor (PlGF) and high amounts of splice variant proteins,
such as sflt-1 that blocks the pro-angiogenic actions of VEGF and PlGF. In addition to these soluble proteins, the syncytiotrophoblast surface
of the placental villi actively secretes a micro-particle fraction, containing exosomes; the latter are 100nm structures that communicate
between cells using surface proteins and protected micro-RNAs. The specific aims of our laboratory are to distinguish the actions of soluble
proteins vs micro-particles in the genesis of severe vascular dysfunction in pregnancy, and to determine the potential non-anticoagulant
actions of heparin that could block adverse signaling pathways between the placenta and the maternal arterial endothelium. The long-term aim
is to create a non-anticoagulant heparin for use in pregnancy ; we aim to direct it to women at most risk of developing severe pre-eclampsia
during the 2nd trimester, such that it’s actions can block the pathways whereby the diseased placental villi prevent the normal hemodynamic
adaptations of the mother.
The research program is funded by CIHR, the Bickell Foundation and Mount Sinai Hospital. It involves pregnant subjects, a small animal
model, explant biology and tissue culture, and an array of molecular biology methods. The research group is small, and comprises a senior
research associate in molecular biology, two PhD students and a research assistant, and is supported by the Placenta Clinic and the Biobank.
The program can accommodate one CREMS Research Scholar over the 20 month period. The research program is ideal for a medical student
who has existing molecular biology skills at the graduate level, and who wishes to utilize these skills in a translational research group with an
interest in reproductive biology.
Directly report to Ms. Dora Baczyk, senior research associate
May be involved in pregnant subject recruitment in the Placenta Clinic or their investigation the cardiovascular laboratory, in small animal surgery (RUPP model)
with tissue and blood analysis, or directly at the bench working in the cell and molecular biology of trophoblast-derived exosomes, including miRNA work
Attend weekly lab meetings, and other academic events
Suited to an individual with graduate training in molecular biology prior to entry to U of T Medicine as a level of independence in the laboratory is essential.
This group has recently had a CREMS scholar student who has generated a manuscript soon to be submitted for publication
SUPERVISOR: Benjamin Goldsten
EMAIL: [email protected]
 FIELD OF RESEARCH: Bipolar disorder, cardiovascular, biomarkers, adolescents
PROJECT TITLE: Imaging-genetics in adolescent bipolar disorder
The focus of this CREMS project is on adolescent bipolar disorder. The selected student will be integrated into the overall
activities of the laboratory, which includes post-doctoral fellows, pharmacology graduate students, undergraduate research
students, and research staff. The student will gain exposure to current methods being applied in the laboratory, including
neuroimaging (MRI), vascular imaging (ultrasound, peripheral arterial tonometry), computerized cognitive testing, serum
biomarkers, genetics, and novel complementary therapeutics. Descriptions of current ongoing studies can be found at the
following website:
Together with the PI, the student will identify a project for which the student will have primary responsibility and firstauthorship. The project will be based on structural brain MRI images and selected candidate genotypes of approximately 90
adolescents (50% with bipolar disorder, 50% healthy controls). The student will be expected to work independently, with input
and guidance from the PI as well as graduate students and post-doctoral fellows. The student will be expected to review the
literature, generate hypotheses, and undertake analyses to test those hypotheses. The student will be encouraged to submit his/her
findings for presentation at a national or international scientific meeting in Canada or the United States. The supervisor and
members of his team will provide guidance and iterative feedback regarding scientific writing in order to support the student in
achieving the goal of at least one peer-reviewed publication during the CREMS period.
Work with and report to PI
Identify a project for which the student will have primary responsibility and first-authorship
Work independently, with input and guidance from the PI as well as graduate students and post-doctoral fellows.
Review literature, generate hypotheses, and analyses to test those hypotheses.
Submit his/her findings for presentation at a national or international scientific meeting in Canada or the United States.
Supervisor and members of his team will provide guidance and iterative feedback regarding scientific writing in order to support the
student in achieving the goal of at least one peer-reviewed publication during the CREMS period
EMAIL: [email protected]
 FIELD OF RESEARCH: Cancer Genomics
PROJECT TITLE: Timing of mutations in pediatric cancer genomes
Childhood cancers are rapidly proliferating tumors whose mutation evolution remains a mystery. My lab uses cutting-edge
sequence-based genomics to study childhood solid and brain tumors to define the type and timing of mutations in cancer. Once
the mutations are temporally ordered, one can begin to differentiate the key oncoproteins involved in tumor initiation versus
progression. Tackling the problem of childhood tumor evolution is necessary to create better predictive models of relapse and
metastasis, from which only a minority of children survive. To understand the genesis of pediatric bone and soft tissue cancers
we will study the mutations that arose long before the patient’s cancer was clinically detected. We will accomplish this objective
through the following two specific aims: Aim 1: To determine the temporal order of DNA mutations in pediatric bone and soft
tissue cancers, and to determine which early genetic lesions alter the subsequent accumulation of mutation. These data will be
used to create a predictive model of cancer relapse. Aim 2: To define the tumor cellular context most permissive for pediatric
bone and soft tissue cancers using a novel RNA sequencing method.
Conduct whole genome analyses, using informatics pipelines and expertise developed by PI’s team.
Motivated students, willing to learn some informatics, will find this to be a very good opportunity to learn cutting edge genomics
SUPERVISOR: Yvonne Bombard
EMAIL: [email protected]
 FIELD OF RESEARCH: Genomics/Health Policy/Health Services/Health Technology/Assessment /Interdisciplinary
Research/Knowledge Translation/Personalized Medicine/Public & Patient Engagement/Qualitative Methods/Survey
PROJECT TITLE: A Genomics Decision Aid (AGenDA): Improving the quality of patient decisions for genome sequencing
Whole genome/exome sequencing (WG/ES) offers promising opportunities to better diagnose a patient’s disease, guide
treatment, predict disease onset and guide disease prevention by assessing hundreds of disease risks in one test. As the test bed of
personalized medicine, cancer care is on the forefront of the clinical translation of WG/ES as cancer centers sequence the
genomes and tumours of their patients to identify therapeutic targets and individualize care. Across Canada, oncologists are
increasingly using WG/ES to target cancer treatment for their patients. However, the process of sequencing the genome of an
individual or their tumour may incidentally reveal information about inherited predispositions to other cancers and
diseases. Increasing policy guidance suggests that ‘medically actionable’ results should be offered to patients undergoing clinical
or research sequencing, with calls to offer additional incidental results if patients prefer. However, it is unknown how to support
patients’ decisions about the scope and scale of results they wish to learn from their WG/ES.. Decision aids (DAs) are ideally
suited to meet this need, given their role in helping patients understand and personalize the various options and to clarify their
values. A DA may improve the quality of decision making and lead to health care savings as an alternative to clinicians spending
hours counselling patients on incidental findings or referring them to GC.
Develop a patient whiteboard video on WG/ES and incidental results
Refine a DA that incorporates the video to guide the selection of WG/ES results
Evaluate the effectiveness of the DA compared to standard genetic counselling
DESIGN & METHODOLOGY: We will use a mixed methods design. For Aim 1, we will use state-of-the-art patient education & health media technology to
develop the whiteboard video that incorporates key concepts of WG/ES, harms and benefits of leaning about incidental WG/ES results. For Aim 2, we will use
the individual interviews with patients to refine a DA. For AIM 3, we will use a randomized controlled trial to evaluate whether the DA reduces decisional
conflict compared to standard GC.
SIGNIFICANCE: This research fills critical quality care gaps by developing and evaluating a novel, patient-centered tool to improve the quality of patients
decisions about learning incidental results when their tumors or genomes are sequenced. This decision support tool can improve delivery of cancer care and
empower patients to enhance their quality of life.
(Students can participate in any of the aims described above)
SUPERVISOR: Marianne Koritzinsky
EMAIL: [email protected]
 FIELD OF RESEARCH: Tumor microenvironment, novel cancer targets
PROJECT TITLE: The role of PRDX4 as a novel therapeutic target in breast cancer
Despite recent advances in cancer diagnosis and treatment, there is still an urgent need to find new specific targets for
novel therapies. One of the approaches is to identify genes that are functionally important in cancer.
Preliminary data from genome-wide screens suggest that Peroxiredoxin 4 (PRDX4) might be a promising target in
multiple cancer types including breast cancer. PRDX4 is an endoplasmic reticulum-localized peroxiredoxin,
responsible for reducing intracellular levels of reactive oxygen species (ROS), such as hydrogen peroxide, protecting
the cellular redox state. This makes the PRDX4 a potential attractive novel target for cancer treatment.
In this project, we will assess the potential of targeting PRDX4 in breast cancer using a genetic approach in vitro and
in vivo. We will establish transient and stable isogenic cell models for PRDX4 using shRNA, monitoring expression
by quantitative RT-PCR and western blotting. We will assess survival, proliferation ROS and molecular stress
responses. This will be achieved using clonogenic assays, automated live-cell microscopy, and flow cytometry. Stable
cell lines with genetic targeting of PRDX4 will be used to establish xenografts in mice. We will monitor tumor growth
as well as biochemical endpoints as above. Finally, using data from functional genomics screens and
sequencing/expression data, we seek to identify biomarkers for sensitivity to PRDX4 targeting.
This project will establish the potential for targeting PRDX4 in breast cancer, and form the basis for future drug
development and patient selection.
Supervised directly by PI. A research associate will aid in training of lab techniques and an animal technician will provide support for in vivo
Student will be integrated in a team of other PDFs and graduate students working on related research questions. (S)he will also be integrated in the
Hypoxia Program at Princess Margaret Cancer Centre which consists of the research groups of ~10 PIs encompassing clinical, biological and physics
translational cancer research
Responsible for the execution of all experiments and data collection. (S)he will present data at project and program meetings and be responsible for
preparing data and text for a manuscript
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SUPERVISOR: Wendy Levinson
EMAIL: [email protected]
PROJECT TITLE: Evaluation of Choosing Wisely Canada STARS (Students and Trainees Advocating for Resource
Choosing Wisely Canada is launching STARS to engage medical students in the campaign. This project will be an evaluation of
STARS and will focus on understanding the impact of STARS across Canada’s medical schools. The evaluation will include
interviews with participating medical students, as well as faculty. There will also be email communication with medical school
contacts. Project outcomes include development of a report detailing interview themes.
The student will directly report to Karen Born, PhD who is Knowledge Translation Lead at Choosing Wisely Canada and holds a
faculty appointment at IHPME. Dr. Brian Wong will also be involved in the supervision of this student.
The student will work with Drs. Levinson, Born and Wong to develop interview guides, as well as undertake interviews with
medical students and other medical school contacts when appropriate. The student will transcribe such interviews and work with
Dr. Born to write up a report on key themes in the interviews. There will ideally be opportunities to publish and present these
findings through peer-reviewed journals and at national and international conferences. This project is supported by a grant from
the American Board of Internal Medicine Foundation, details here:
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EMAIL: [email protected]
 FIELD OF RESEARCH: MRI in Multiple Sclerosis
PROJECT TITLE: Structural and Functional Correlates of Disability in the Spinal Cord in Progressive and Relapsing
Remitting Multiple Sclerosis: A Longitudinal Study
The spinal cord (SC) is a common site of lesion formation in multiple sclerosis (MS) and a compact structure organized into discrete columns that mediate
specific sensorimotor functions. Lesionsi in the SC have the potential to cause substantial deficits, making it an ideal substrate to study structure-function
relationships in MS. Particularly in progressive variants of MS, including primary progressive MS (PPMS) and secondary progressive MS (SPMS), the SC
carries a heavy burden of disease. As such, the SC is an important region to assess to better under disease processes in both progressive and relapsing MS,
which remain elusive. A better characterization of MS disease processes is necessary to develop an effective treatment for progressive MS, which does not yet
exist, making it the greatest unmet need in the clinical management of MS. In addition, targeted, more efficacious treatments for relapsing MS can be
developed with improved insights into MS disease processes.
In recent years, a number of advanced, quantitative MRI techniques, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI)
have demonstrated increased sensitivity to underlying tissue microstructural properties in comparison to conventional MRI techniques. Another essential
consideration that has not yet been explored in detail in the SC in MS subjects is the functional status of damaged tissue, as significant re-organization of
neural networks relevant to specific neurological functions occurs after MS-related tissue damage. Accordingly, including a functional assessment of damaged
tissue, utilizing functional MRI (fMRI) or positron-emission tomography (PET) may be a key piece in the puzzle to better understand disease mechanisms in
progressive MS.
In this study, we propose to combine quantitative structural and functional measures in the SC in a large cohort of MS subjects, including those with PPMS,
SPMS, and relapsing-remitting MS (RRMS).
This proposal is innovative as the vast majority of SC MRI studies in MS have focused on probing structural changes alone in the SC, but have not included
an assessment of functional changes, which may be an important link to understand MS disease mechanisms. In addition, longitudinal changes using
advanced, quantitative SC MRI measures have only been assessed in a few prior studies which have included small numbers of MS patients. Establishing
strong longitudinal correlations between changes in quantitative SC MRI measures and clinical change is an essential step to further develop the use of these
techniques as surrogate outcome measures in trial settings, and as tools for clinical monitoring and prediction in the management of MS patients. Finally,
because there are no existing studies that have utilized combined PET-MRI in the brain or SC of MS subjects, we are proposing to assess the utility of this
novel technology in a pilot feasibility study of a subset of MS patients included in the parent cohort.
We expect that using a combination of advanced structural and innovative functional measures will enable a more thorough characterization of disease-related
change in the SC in both progressive and relapsing MS that are intimately linked to clinical disability. Accurately characterizing the structural and functional
substrates of disability is an essential stepping-stone that will allow for the development of targeted treatments in both progressive and relapsing MS, and the
use of these measures as surrogate outcome measures in progressive MS clinical trials.
Acquire an understanding of clinical research methodology (patient recruitment, research ethics, obtaining informed consent, study visit
protocols, data collection and extraction).
To acquire an understanding of and apply principles of data acquisition and analysis in imaging-based research in MS
To apply basic biostatistics principles to address a scientific hypothesis
To acquire the ability to present scientific results in oral and written format in a clear and concise manner
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SUPERVISOR: Lorraine Kalia
EMAIL: [email protected]
 FIELD OF RESEARCH: Neuroscience (Parkinson’s disease)
PROJECT TITLE: Molecular mechanisms of parkinsonism
Parkinson’s disease (PD) is a common and disabling neurodegenerative condition. Its clinical presentation is defined by Parkinsonism (i.e. bradykinesia, rigidity,
tremor, and postural instability). Symptomatic treatments are available for patients to alleviate these symptoms. Yet, there is an absence of therapies which
modify disease progression by slowing or stopping the neurodegenerative process. I am a clinician-scientist with a research program in PD. My lab’s major
research objective is to elucidate the critical molecular mechanisms responsible for neurodegeneration in PD and related disorders. The ultimate goal is to target
these molecular pathways for rational drug design and development of disease-modifying therapies.
One of my strategies to discover novel pathways involved in the neurodegenerative process associated with PD is to study rare genetic conditions associated
with Parkinsonism. There is a growing list of genes that, when mutated, can be associated with many of the features of idiopathic PD. The proposed project for
the student will be to determine how specific mutations in one or more genes may contribute to neurodegeneration using patient-derived fibroblasts. Previous
experience with cell culture techniques would be an asset.
My lab is in the Toronto Western Research Institute and is affiliated with the Tanz Centre for Research in Neurodegenerative Diseases. The lab space is located
within the Krembil Discovery Tower which is a new state-of-the-art research building with an open-concept lab design to support interactions between different
research groups. The medical student will be a member of my lab team which works closely with two other clinician-scientist led labs in the Krembil Discovery
Tower with a focus on PD and related neurodegenerative disorders.
Review the literature on the specific genes involved in parkinsonism
Attend mandatory orientations including laboratory and safety training
Read papers and book chapters on laboratory techniques that are new to the student
Perform the following experimental techniques: cell culture (maintenance, transfection), SDS-PAGE, Western blots, microscopy + cell
assays (e.g. cell death, mitochondrial function, proteasomal function, lysosomal function)
Troubleshoot experiments (with assistance from others as needed)
Interpret the results of experiments (with assistance from others as needed)
Attend and participate in weekly lab meetings
Write a final report of the project (with the goal of having a publication in a peer-reviewed journal)
Attend research rounds (optional)
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SUPERVISOR: Istvan Mucsi
EMAIL: [email protected]
 FIELD OF RESEARCH: Kidney transplantation / outcomes research / patient reported outcomes
PROJECT TITLE: Ethnocultural barriers to living donor kidney tranplantation
We will investigate readiness to accept living donor kidney transplant (LDKT) and also ethnocultural barriers to
accepting LDKT in patients with chronic kidney disease (CKD). The new knowledge generated in our study will inform
the development of personalized, culturally appropriate education tools to facilitate equal access to LDKT. In 2013 over
23,000 Canadians were treated with dialysis but only about 15% of these patients were wait-listed for kidney transplantation
(KT). Compared to deceased donor kidney transplantation, living donor kidney transplantation (LDKT) is the optimal treatment
for suitable patients with end stage kidney disease (ESKD): the wait time is shorter and the prognosis is better. Only 30-40% of
kidney transplant recipients, however, will receive LDKT in Canada. Approximately 10% of Canadians have CKD and 30-35%
of these patients in Ontario are of East Asian, South Asian or African Canadian background. Compared to Caucasians, ethnic
minorities are less likely to receive a KT and even less likely to undergo LDKT. The reasons for this ethnic disparity are
unknown. Modifiable psychological problems such as depression may contribute. Insecure attachment style, an important
determinant of interpersonal and patient-provider relationship, may also prevent effective communication between patients and
potential living donors. Socio-economic, cultural and religious factors may also play a role. In this study we will utilize a mixed
methods approach: we will assess potentially modifiable psycho-social factors, transplant knowledge and readiness to accept
LDKT using validated questionnaires in a relatively large cohort (5-600) of patients who are referred for assessment of their
kidney KT candidacy. Ethnocultural barriers to accepting LDKT will also be assessed employing qualitative research
methodology in a subset of patients.
Hypotheses to be tested in the quantitative study: Primary hypothesis: Depressive symptoms in the potential recipient is
associated with reduced odds of having a potential living donor identified and less readiness for LDKT at the time of presenting
to the kidney transplant centre for evaluation. Secondary hypothesis: Compared to Caucasians, patients of East Asian, South
Asian or African Canadian background are less likely to have a potential living donor identified and are less ready for LDKT at
the time of presenting to the kidney transplant centre for evaluation.
In the qualitative arm we will investigate the ethno-cultural barriers to LDKT in patients of East Asian, South Asian or African
Canadian background. The paucity of literature about these ethnic groups, particularly those living in Canada, precludes the
development of meaningful hypotheses at this stage. We will use focus groups to generate new knowledge about verbal and nonverbal attitudes and beliefs among patients of East Asian, South Asian or African Canadian background pertinent to LDKT. This
information could not be fully captured with questionnaires and the focus group study methodology will facilitate expeditious
collection of a large amount of data in a relatively short timeframe.
Literature review; enrolling patients; collecting data using electornic data capture system; data entry; data cleaning; analysis of data using
STATA statistical analysis software; preparing abstracts, posters for conferences; writing papers
Student will report directly to PI
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SUPERVISOR: Ilana Halperin
EMAIL: [email protected]
 FIELD OF RESEARCH: Quality Improvement
PROJECT TITLE: Implementation and evaluation of a balanced diabetes scorecard
The Institute of Medicine (IOM) defined quality in health care as having six domains: safety, effectiveness, patient-centeredness,
timeliness, efficiency, and equitable care. Yet, commonly used biologic and process metrics for quality in diabetes care largely
address the “effectiveness” domain with discordance between commonly reported metrics and stakeholder priorities. In earlier
phases of work we have used qualitative methodology, literature reviews and a modified Delphi panel to arrive at a list of quality
indicators that represent the six domains of quality. The next phase is to pilot test data collection (should be completed by the
spring of 2015). After that we will begin the process of large scale data collection to produce the first of what will be regular
score cards to monitor and improve upon quality of diabetes care in the ambulatory specialty clinics at UofT.
The student would help in the role out data collection across multiple sites at the University of Toronto. They would be
involved in analyzing the data and determining benchmarks. There is a science to audit and feedback and the student
would help to determine the best ways to provide the data back to the clinics and individual physicians and help to
conduct qualitative interviews with stakeholders as to the utility of the benchmarking and scorecard process. Time
permitting the student may also help to develop and start quality improvement projects based on the outcomes of the data
collection process.
The student will learn about quality improvement and audit and feedback methodologies. Skills required are creativity,
critical thinking and ability to work independently.
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SUPERVISOR: Gregory H. Borschel
EMAIL: [email protected]
 FIELD OF RESEARCH: Peripheral nerve repair and regeneration
PROJECT TITLE: Corneal neurotization: Investigating a novel surgical approach to prevent blindness in patients with corneal
anesthesia and neurotrophic keratopathy
The student would help in the role out data collection across multiple sites at the University of Toronto. They would be involved
in analyzing the data and determining benchmarks. There is a science to audit and feedback and the student would help to
determine the best ways to provide the data back to the clinics and individual physicians and help to conduct qualitative
interviews with stakeholders as to the utility of the benchmarking and scorecard process. Time permitting the student may also
help to develop and start quality improvement projects based on the outcomes of the data collection process.
The student will learn about quality improvement and audit and feedback methodologies. Skills required are creativity, critical
thinking and ability to work independently.
The student will be responsible for a small project contributing to investigating corneal neurotization under the direct
supervision of a PhD student in the lab, who is primarily responsible for the project. On a daily basis, the student will be
directly supervised by our lab manager and graduate students. Additionally, the student will meet with the Principal
Investigator (GHB) on a weekly basis to review progress, results and discuss and issues with the experiment. The student
will be expected to present their work at lab meetings and, depending on the success of the project, will have an
opportunity to present their work at international and national conferences once completed. The student will have their
own space within the lab and will be additionally supported by lab technicians and post-doctoral fellows that can assist
with learning techniques and trouble-shooting. The student will have additional opportunities to observe the surgical
procedure in the OR and attend divisional rounds at SickKids for the Division of Plastic and Reconstructive Surgery.
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SUPERVISOR: Douglas Cheyne
EMAIL: [email protected]
 FIELD OF RESEARCH: Neuroimaging (MEG, MRI)
PROJECT TITLE: Imaging brain activity in children with stroke
We are conducting a 3-year CIHR funded project using human neuroimaging measurements (Magnetoencephalography (MEG)
combined with functional and structural MRI scans) in children recovering from stroke with hemidystonia or other motor
Currently there is little understanding of why some stroke patients develop dystonic or hypertonic symptoms – abnormal muscle
tone or posture – usually appearing several months following their stroke, and why this is more prevalent in children. The goal
of this research is to apply neuroimaging measures during targeted sensory and motor tasks to help identify the neural
mechanisms underlying the development of hypertonia in these patients, and possibly provide predictors of outcome. The
children will undergo a single session of non-invasive functional brain imaging during sensory stimulation tasks designed to
assess the excitability of the sensorimotor system. During the imaging session children will also receive continuous tactile
stimulation of their affected hand. This technique has been shown to help induce neuroplasticity in the sensorimotor system and
we will assess its efficacy in inducing short-term changes in the associated brain responses. Participants are being recruited from
existing clinical populations and databases at SickKids and undergo neurological assessment for motor function and
hypertonicity. Selected patients will be scanned on a research-dedicated 151-channel MEG system and 3.0 T Siemens MRI
scanner, both located at the Hospital for Sick Children in Toronto. We will also use functional MRI (fMRI) and other structural
MRI measures, such as diffusion tension imaging and cerebrovascular reactivity (CVR) to assess the integrity of neural function
in sensory and motor regions of the brain in these children. The principal investigator Dr. Douglas Cheyne is a neuroimaging
scientist with specialization in movement studies at the Hospital for Sick Children Research Institute (
This project is being conducted in collaboration with clinicians and scientists at the Hospital for Sick Children Neurology
department, including co-investigators Dr. Gabriel DeVeber, Dr. Nomazulu Dlamini, and MRI physicist Dr. Andrea Kassner.
We are seeking a motivated individual with basic computing skills, a keen interest in learning neuroimaging methods and signal
processing techniques, and working with pediatric populations to assist with data organization and analysis of imaging data. The
student will have the opportunity to interact with all members of our research team, and will be exposed to all aspects of the
project, including neurological assessments in patients, acquisition and analysis of functional brain imaging data, and preparation
of initial study results for publication in peer-reviewed journals. This will be an ideal opportunity for a student wishing to gain
exposure to advanced brain imaging technology, and its use in pediatric stroke populations.
The student will report directly to project Dr. Douglas Cheyne at the Hospital for Sick Children Research Institute. The student will be provided with
workspace at the PI’s laboratory at the Peter Gilgan Centre for Research and Learning located at 686 Bay St. in downtown Toronto. The student will be
expected to attend monthly project meetings, and will work closely with research coordinators, postdoctoral fellows, and Sickkids medical and support staff
during the course of the project, including helping with data collection in the Neurology clinic and imaging facilities at SickKids. During the first phase of the
Scholar program the PI and student will identify specific goals for the summer work terms, which may include both MEG and MRI imaging data and clinical
protocols. It is anticipated that the assigned work will lead to at least one research publication by the end of the student’s program.
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EMAIL: [email protected]
FIELD OF RESEARCH: Health Services Research
PROJECT TITLE: Screening While You Wait (SWYW): Tablet-based, Patient-initiated health practice screening in primary
care waiting rooms
Lifestyle assessment is a cornerstone of preventative healthcare and primary care. One such behavior, physical inactivity, is strongly implicated in the development and progression of myriad
health conditions leading to morbidity and mortality. As champions of preventive medicine, it is our responsibility to effectively assess physical activity levels as a vital sign and provide
appropriate intervention where appropriate.
Studies have repeatedly shown that despite general knowledge of the benefits of physical activity, healthcare providers are relatively ineffective in the assessment of physical activity and provision
of appropriate intervention for sedentary individuals.
We have an opportunity to adopt novel technology in Family Practice to support patient-initiated self-assessment of health practices. The use of tablet-based software allows for patient data to be
fed directly into the patient chart to facilitate prioritization of health behavior and counseling by healthcare providers. This technology offers two benefits: patient engagement in their care, and the
possibility of creating more efficient processes. This tablet-based technology has been successfully adopted in other TAHSN Family Health Teams.
The overarching goal of our project is to fully integrate tablet-based, patient-initiated self-assessment into routine clinical care at Family Practice, in order to support meaningful health behavior
change in our patients. If successful, this project could be adapted to multiple programs.
As a first step, our team will pilot this strategy on a small scale targeting physical activity behaviour, in order to establish: 1) content and acceptability 2) evaluate effectiveness and 3) adopt the
approach to other health needs
The components of this pilot project can be broken down into three main components:
Develop Content and Assess Patient and Provider Acceptability (Phase 1)
Develop physical activity screening questionnaire
Integrate screening questionnaire into tablet interface
Develop clinical decisional support algorithm (based on risk stratification)
Collection of codified resources
Develop process & resources to facilitate referrals for patients who would benefit from additional support
Patient usability and satisfaction
Provider satisfaction
Research – Evaluate Effectiveness (Phase 2)
This phase would involve the initiation of a research project that will test the hypothesis that this lifestyle screening tablet initiative will have a positive impact on physical activity outcomes.
Tablets have the potential to be used as a powerful tool for collection of research data in the primary care environment.
Develop protocol
Consent & recruit participants
Knowledge transfer
Adapting to other health needs (Phase 3)
This phase involves adapting phase 1 and 2 and applying them to other health needs, beyond physical activity. Adapting the approach for physical activity to other health needs tests the full
potential of actively engaging patients in inputting their own health data into their electronic health record.
Environmental scan – determine which PROMs exist for the tablet, and which PROMs are commonly used for direct entry into EMRs. Based on this, determine which health
issue to address next
Adaptation – adapt PROM and process to new health issue
Test – test approach on a small scale
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SUPERVISOR: Simone Vigod
EMAIL: [email protected]
 FIELD OF RESEARCH: Women’s mental health, Psychiatry
PROJECT TITLE: Interventions to reduce or prevent obesity during pregnancy among women with mental illness
Obesity during pregnancy is associated with negative maternal and child outcomes, including gestational diabetes mellitus and
macrosomia. Up to 30% of obese women demonstrate clinically significant depressive symptoms during pregnancy and the
postpartum period. Depressive symptoms such as low mood, lack of motivation and negative thinking patterns may interfere
with efforts to reach and maintain a healthy body weight. Lifestyle interventions such as diet and exercise are moderately
effective at reducing or preventing obesity during pregnancy and its negative consequences. However, the efficacy of these
interventions for women with depressive symptoms is unknown. Further, while psychotherapeutic interventions such as
cognitive behaviour therapy (CBT) have been used for treatment of obesity in depressed and non-depressed populations, to our
knowledge this type of intervention has not been adapted for the purpose of reduce and/or preventing obesity in pregnancy. The
goals of this project are to: 1) systematically review the scientific literature with respect to the efficacy of existing interventions
to reduce and prevent obesity during pregnancy among women with depression; and 2) design and execute a pilot randomized
controlled trial of a psychotherapeutic intervention to reduce and prevent obesity during pregnancy among women with
Dr. Vigod will serve as the primary supervisor for this CREMS project, with consistent input from co-supervisors Dr. Taylor
(expertise in psychotherapeutic interventions for obesity) and Dr. Dennis (expertise in systematic reviews and perinatal treatment
trials) around study objectives and findings. Dr. Vigod’s team also includes a post-doctoral fellow (Dr. Hilary Brown, PhD) who
will assist the student closely with the design and conduct of the systematic review; as well as a senior research coordinator (Ms.
Neesha Hussain-Shamsy) who will assist the student closely with preparation of research ethics board applications, study
documents, manuscripts and presentations. With the support of this team, the student will develop a protocol for the systematic
review, adhering to PRISMA guidelines, and conduct the review (which may include meta-analytic statistics) with the support of
the experienced team. The student will then be expected to present these findings in hospital rounds for feedback, submit a
manuscript for publication (as first author), and to present at a scientific conference. In consultation with the study team and
other stakeholders, the student will then be primarily responsible for authoring a protocol for a pilot randomized controlled trial
of an intervention to be delivered for obese women with depression who are planning a pregnancy or who are currently pregnant.
We expect that this protocol will be published in a journal such as TRIALS, and that the student will lead the preparation of an
REB application and study documents to prepare for the evaluation of the intervention. If time allows, the student will also be
able to play a central role in the conduct of the evaluation, and subsequent research products.
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SUPERVISOR: Andrea Kassner
EMAIL: [email protected]
 FIELD OF RESEARCH: Neuroimaging, Cerebrovascular disorders
PROJECT TITLE: Structural and functional changes in the adolescent rodent brain in treptozotocin induced type 2 diabetes
Type 2 diabetes mellitus (T2DM) was formerly a disease associated with adulthood and old age. However, due to the increase in
high fat diets and decrease in physical exercise, it is now recognized to also affect younger populations. Type 2 diabetes is a form
of insulin resistance associated with serious long term complications including vascular disease, neurodegeneration and cognitive
impairment, although the underlying mechanisms and dynamics are not well understood. By using an established high fat
diet/Streptozotocin (HFD/STZ) rodent model of T2DM, we will be able to investigate the cerebral pathophysiology while
controlling for genetic and environmental factors. We will focus on an adolescent rat population and use MRI to quantify
changes in cerebral structure, blood brain barrier (BBB) integrity and hemodynamics. These changes will be correlated with
cognitive decline, as measured with a Novel Object Recognition test. We will also assess the potential therapeutic effect of Largenine (known to increase the bioavailability of nitric oxide). Post-mortem studies will enable us to assess inflammation and
perform neuron counts. Our aim is to provide a thorough pathophysiological profile across T2DM in adolescent rats offering
insight into the physiological mechanisms which underlie this disease.
Type 2 diabetes mellitus (T2DM) was formerly a disease associated with adulthood and old age. However, due to the increase in
high fat diets and decrease in physical exercise, it is now recognized to also affect younger populations. Type 2 diabetes is a form
of insulin resistance associated with serious long term complications including vascular disease, neurodegeneration and cognitive
impairment, although the underlying mechanisms and dynamics are not well understood. By using an established high fat
diet/Streptozotocin (HFD/STZ) rodent model of T2DM, we will be able to investigate the cerebral pathophysiology while
controlling for genetic and environmental factors. We will focus on an adolescent rat population and use MRI to quantify
changes in cerebral structure, blood brain barrier (BBB) integrity and hemodynamics. These changes will be correlated with
cognitive decline, as measured with a Novel Object Recognition test. We will also assess the potential therapeutic effect of Largenine (known to increase the bioavailability of nitric oxide). Post-mortem studies will enable us to assess inflammation and
perform neuron counts. Our aim is to provide a thorough pathophysiological profile across T2DM in adolescent rats offering
insight into the physiological mechanisms which underlie this disease.
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SUPERVISOR: Anne Bassett
EMAIL: [email protected]
 FIELD OF RESEARCH: Genetics; Complex disease
PROJECT TITLE: Identifying genetic and clinical predictors for congenital cardiac and other common diseases
There is a large genetic component to risk for developmental conditions, including those involving the heart and the brain. The
identification of clinical and genetic markers for these diseases would allow earlier diagnosis and development of more effective
treatment and potentially preventive strategies. We study human genetic models that significantly increase the power to identify
such markers. Working at the University Health Network and Centre for Addiction and Mental Health, and with colleagues at
The Centre for Applied Genomics (SickKids), our patient populations and extensive genetic and clinical data offer the
opportunity to discover new pathways to fundamental disease mechanisms. Resources include next generation DNA sequencing
data, comprehensive clinical and imaging data, longterm outcome data, and patient populations with tetralogy of Fallot and other
congenital cardiac diseases, including those with specific genetic subtypes. These clinical and statistical/bioinformatics based
research results have the potential to be immediately translated into clinical practice and have public health implications.
The student will have the opportunity to formulate a research question of interest within the framework of our existing resources
and patient populations. Suggested topics include detecting late onset conditions in 22q11.2 deletion syndrome and delineating
variable expression. Responsibilities will include designing the specific details of the project, coordinating the data collection and
analysis, presenting their work at local and/or international venues, and writing a manuscript suitable for publication in a peerreviewed medical journal. Students may have the opportunity to interact with patients in a clinical context, and to hone
assessment and related skills. The student will report directly to the PI who provides substantial mentorship and guidance.
Collaborators and graduate students are also available to the student.
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SUPERVISOR: Thomas Forbes
EMAIL: [email protected]
 FIELD OF RESEARCH: Translational studies related to aortic surgery, with a focus on endeavor aneurysm repair
PROJECT TITLE: Development of translational computational models of fenestrated aortic stent graft delivery and
The student will be part of a multidisciplinary (Mechanical Engineering, Vascular Surgery, and Interventional Radiology), and multiinstitutional (University of Toronto, Université de Montréal, and University of Calgary) team working on understanding the causes of and
predicting the occurrence of fenestrated aortic stent graft rotation during deployment. When these devices rotate, the fenestrations (holes) in
the device that allow blood flow to the branch arteries become misaligned, which can occlude these vessels and lead to complications such as
renal failure or bowel ischemia. We hypothesize that these devices rotate upon deployment due to a build-up of rotational energy during
delivery through iliac arteries that are tortuous, calcified and/or stenosed. We will use a combination of clinical, experimental, and
computational data to study rotation of these devices to meet our research goals. The student will be part of the team working on the
computational aspects of this project, which are described below.
Using the commercial finite element software, ANSYS LS-DYNA, we will simulate the delivery and deployment of standard (no
fenestrations) and fenestrated aortic stent grafts in idealized and patient-specific anatomical models. We will calculate the amount of rotation
of each device following deployment and compare these calculations with measurements made in our experimental studies and estimate found
from clinical cases. Once validated, we will use our computational studies to determine which factors (geometric and mechanical properties
of the iliac arteries, geometric and mechanical properties of the stent graft) contribute to device rotation. By doing so computationally, it will
enable us to vary parameters such as the coefficient of friction between the device and its delivery system, that cannot be easily varied
experimentally to determine their impact on the rotation. Ultimately, we will use this information to suggest design modifications to stent
graft manufactures that would reduce rotation in future devices.
We also plan on developing our computational models with an eye towards having them be used clinically as part of the preprocedural
workflow for fenestrated aortic stent graft implantation procedure to predict in which cases rotation may occur to mitigate complications
associated with this rotation, improve patient outcomes, and reduce operative time and costs. Automation of the steps involved in setting up
and executing these simulations will be an essential part in having our models adopted clinically over the long-term.
The student's role will be to work on creating a digital library of commercial fenestrated aortic stent grafts with tools to generate computational models of
these devices, select their sizes, and specify the location of the fenestrations (year 1)
The student will also be responsible for developing computational toolboxes to automate medical image segmentation, mesh generation (for the arteries and
the devices), simulation set-up, and simulation execution (year 2).
A strong computer programming background is required for this position. Ideally, the student will have experience with engineering or computer science
principles. Knowledge of medical image segmentation, the finite element method, and the use of ANSYS Workbench and/or LS-DYNA, would be
considered assets, but not requirements for this position.
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SUPERVISOR: Lianne Singer
EMAIL: [email protected]
 FIELD OF RESEARCH: Clinical / outcomes research in organ transplantation and advanced lung disease
PROJECT TITLE: New approaches to Evaluating Frailty in Solid Organ Transplantation
The overall objectives of this research program are to develop and validate novel multi-dimensional frailty indices for organ
transplant donors and recipients based on cumulative deficits. The CREMS student project will be development of the donor
frailty index. We hypothesize that a donor frailty index can be developed from routine data elements collected at organ donation
and will be associated with number of organs used for transplantation, as well as established organ-specific donor risk scores. We
will develop these indices though a retrospective cohort study of deceased organ donors.
Organs from frail donors may be more vulnerable to the many stresses of transplantation including donor critical illness and brain
death, organ procurement, organ ischemia and reperfusion, and alloimmune and non-alloimmune graft injury. Older donor organs
may be more susceptible to dysfunction due to age-related injury and impaired stress responses, reduced repair capacity, and
increased immunogenicity. Though comprehensive clinical data are obtained to evaluate deceased donors, there have been no
published attempts to quantify overall donor frailty using a multidimensional approach.
Deceased donor data (i.e., demographics, clinical history, laboratory values, microbiology, pathology, and donation process
measures) used by transplant physicians and surgeons at the time of organ offer to determine suitability for transplantation have
been electronically collected in Ontario by Trillium Gift of Life Network (TGLN) since April 23, 2013. A donor frailty index
will be developed using the methods developed by Kenneth Rockwood and colleagues (Dr. Rockwood is one of our study coinvestigators). We will include 100 consecutive donors. Feasibility will be defined as ability to generate a frailty index for 80%
of eligible donors.
We will examine Spearman correlations between frailty index and number of solid organ types (kidney, lung, liver, heart,
pancreas) used for transplantation. We will also measure associations between donor frailty index and established risk scores for
lung, liver, kidney and heart donors. With 80 donors, we will have 80% power to detect correlations of 0.3 or greater. We will
also assess the predictive validity of the donor frailty index by evaluating associations with graft function and post-transplant
survival after adjustment for recipient factors.
The student will be responsible for all aspects of the donor frailty index study including finalizing the study protocol, data
collection, data analysis and presentation and publication of study results. Dr. Singer, the PI, will be the student’s direct report.
Dr. Singer’s CREMS supervisory experience includes two students, both of whom first authored publications in high-impact
journals. The student will also work closely with Noori Chowdhury, the study coordinator, and other students involved with this
research program. This study involves investigators from all the solid organ transplant programs (lung, heart, liver, kidney) and
the student will participate in meetings of the investigator group and the UHN Multi-Organ Transplant Program Outcomes
Research Group, which is chaired by Dr. Singer. This study is funded by the Technology Evaluation in the Elderly Network of
Centres of Excellence (TVN) and the budget includes funding specifically for a CREMS student for this project. TVN also
provides a unique interdisciplinary training program which includes learning modules and regular network/trainee meetings. The
CREMS student will also have the benefit of participation in this national training program. Further details are available here:
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SUPERVISOR: David Wiljer
EMAIL: [email protected]
 FIELD OF RESEARCH: Health informatics; Health Services Research; Knowledge Translation; Client and Family
PROJECT TITLE: Evaluating mHealth Interventions for mental health concerns and problematic substance use
The student will have the choice of working on an evaluation of either below mhealth intervention. The evaluation will use a mixed methods approach giving the student
exposure to both qualitative and quantitative research methods.
1.) Thought Spot mHealth Intervention:
Intervention: This project, co-created by students, will evaluate the open-source online and mHealth intervention (Android and IOS), Thought Spot, that aims to enable
transition-aged youth in postsecondary settings to identify and overcome barriers to obtaining help for mental health related issues. The aim of the mHealth intervention is to
enhance help-seeking for mental health support and services, and thereby increase their utilization of appropriate services. Using a holistic definition of mental health, usergenerated information is offered on over 1000 mental health and wellness “spots” (e.g., campus health centres, addiction services, yoga studios).
Research Design: Using a randomized controlled study design, we will test the hypothesis that students using Thought Spot will have greater improvement in self-efficacy
towards help-seeking for mental health concerns compared to the control group. The intervention arm will have access to the Thought Spot platform and the control arm will
receive usual care (access to campus health services, web and print-based health materials). Data will be collected from participates at 3-4 intervals throughout the study using
several validated scales (e.g. General Help-Seeking Scale, Self-Stigma of Seeking Help, Mental Health Confidence Scale). We will also gather data on demographics, general
mental health status (GAIN-SS-Canadian/ CAMH version), and technology use comfort and ability (study team to develop Technology Use Questionnaire) to examine trends,
comparisons and correlations between the study groups.
2.) Saying When App:
Saying When, available as a workbook or mobile app, helps those who want to cut back or quit drinking manage their drinking habits in real time. Based on an established selfmonitoring program from CAMH, the audience is meant for individuals that are concerned about their drinking but do not have a severe substance use disorder. There are
several key features of the Saying When app: introduction to the Canadian Low Risk Drinking Guidelines; a function called "Taking Stock" which lets people identify current
habits to help set goals; infographics that describe and define standard drink sizes; tracking features where people can enter the drinks they consume and then monitor the
quantity of drinks; and a coping section that shows which approaches work best for the user when they are trying to cut back or quit drinking.
Research Design: This pilot study will explore patients’ perceptions of usefulness and feasibility of the intervention. This study will be implemented as part of the existing
assessment process for the CAMH Outpatient Concurrent Addiction Treatment (OCAT) Service and will offer a set of self-help tools (the app, the book and perhaps a web site)
to the patients that are waiting in queue for treatment at OCAT. This is a qualitative study where patients are interviewed at the beginning and end of their wait time to find out
about their perceived ease of use and usefulness of these tools, as well as their knowledge gain as a result of using these tools. Semi-structured interviews will be held with
participants pre- and post- intervention. Mobile app analytics will also be analyzed.
Developing and submitting REB application (CAMH and/or U of T)
Developing interview guides and/or survey instruments
Conducting literature reviews and/or environmental scans
Developing a recruitment and engagement strategy and corresponding materials
Actively recruiting and screening potential participants, and obtaining informed consent
Qualitative (NVivo) and quantitative data analysis (SPSS) of data
 Research manuscript writing and publishing
The student will directly report to David Wiljer and will be supported by the Manager and Research Coordinator of the Client and Family Education Program at CAMH
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EMAIL: [email protected]
 FIELD OF RESEARCH: Thombosis/Hemostasis, transfusion medicine, immunology
PROJECT TITLE: Novel mechanisms and treatments of thrombosis and thrombocytopenias
Platelet adhesion and aggregation at sites of vascular injury are key events required for platelet plug formation and arrest of
bleeding (hemostasis). Insufficient platelets in the blood (thrombocytopenia) may lead to severe bleeding. Conversely,
pathological platelet plug formation may lead to thrombosis; the most common cause of heart attack and stroke following
atherosclerotic lesion rupture. These, including platelet-related deep vein thrombosis are leading causes of mortality worldwide.
The student will have the opportunity to learn the state-of-art in vitro and in vivo approach used in my lab to analyze mechanisms
and novel treatment of thrombosis and thrombocytopenias. With our unique pre-clinical in vivo models, especially the intravital
microscopy models, my laboratory is an excellent training site for medical students who want to become future clinical scientists.
The student will under direct supervision of a post-doc fellow or research staff to initiate the project. The student is expected to
perform majority of the experiments independently after 2-3 weeks training in the laboratory.
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SUPERVISOR: Lorraine Libscombe
EMAIL: [email protected]
 FIELD OF RESEARCH: Diabetes prevention, gestational diabetes, lifestyle modification
PROJECT TITLE: Avoiding Diabetes after Pregnancy Trial in Partners (ADAPT-P)
This is a sub-project of the Avoiding Diabetes after Pregnancy Trial in Moms (ADAPT-M). ADAPT-M is a randomized controlled trial that is evaluating a 6-month lifestyle
modification program for postpartum women with recent gestational diabetes mellitus, to help lower their risk of future diabetes. The goal of the study is to evaluate whether the
ADAPT-M program will reduce diabetes risk factors for high-risk new mothers compared to usual care. However, we also see our program as an opportunity to improve the
health and lifestyle of mothers and families. Healthy behaviour changes in mothers may influence the dietary and physical activity habits of the entire family. Specifically,
evidence shows that diet and physical activity are highly influenced by the attitudes, behaviour, support, and health of significant others. There is little evidence regarding the
extent to which behavioural interventions aimed toward mothers can lead to positive behavioral changes and improved risk factors in their household partners. We hypothesize
that the partners of women who receive our program will be more likely to make positive behaviour changes and have improved metabolic outcomes compared to the partners of
women randomized to the control group. There is also evidence that women are more likely to adhere to lifestyle changes if they have high spousal support. In that context, we
also hypothesize that women whose partners agree to participate in the study will have greater adherence and better outcomes compared to women whose partners do not agree
to participate. Women who feel supported by their partners are more likely to adhere to changes, and parents are more likely to set good examples for their children if both are
engaged in a healthy lifestyle. Such data would have significant implications for the potential impact of our program. To address these issues, “Avoiding Diabetes After
Pregnancy Trial in Partners (ADAPT-P)” will evaluate the behaviour and metabolic outcomes of partners of ADAPT-M participants before and after the study as secondary
outcomes of ADAPT-M. As a secondary objective, we will compare behavioural and metabolic outcomes of ADAPT-M participants between those whose partners do and do
not agree to be evaluated as a surrogate measure of partner support. If partners are also being evaluated at baseline and study end, they may be more motivated to support and
participate in their female partners’ diet and physical activity changes throughout the study. Participants of ADAPT-M are recruited during pregnancy and enrolled in the trial at
6-12 weeks postpartum. Participants will be asked for consent to contact their partners regarding participation in ADAPT-P. Partners of consenting women will be invited to
attend a baseline behavioural and metabolic assessment prior to their spouses’ initiation of the program, half-way through the program (12 weeks), and following completion of
the program (24 weeks). Assessments will include a detailed demographic, clinical, and behavioural questionnaire, a physical assessment, and venipuncture for fasting glucose,
insulin, HbA1c, and lipid profile. Recruitment and baseline assessments will be completed by June 2016, and final data will be collected by June 2017.
The student will report directly to Dr. Lorraine Lipscombe, Principal investigator for the ADAPT-M and ADAPT-P studies.
During the first summer period (2016), the student will have the following responsibilities: analyze baseline ADAPT-P data; analyze baseline ADAPT-M data to compare
characteristics of women with participating partners and non-participating partners; conduct an updated literature review; prepare a manuscript of these findings; and develop a
questionnaire that will be administered to both members of the dyad at the end of the study. Throughout the 2016-2017 academic year, the student will continue work on these
tasks and will have the opportunity to assist in the day-to-day operations of the ADAPT-P program. During the summer of 2017, the student will analyze the complete dataset
from the ADAPT-P study, comparing data between the dyads randomized to an intervention group to those in the standard care group, and prepare an abstract of these findings
to present at a national meeting (e.g. CDA), and prepare a manuscript of these findings.
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SUPERVISOR: Mathieu Lemaire
EMAIL: [email protected]
 FIELD OF RESEARCH: Nephrology, Rare pediatric kidney diseases (aHUS), DGKE
PROJECT TITLE: Pathophysiology of DGKE-associated atypical hemolytic-uremic syndrome
Our lab has two main "arms". First, we have expertise in doing gene discovery using whole exome sequencing focusing on
patients with rare pediatric kidney diseases. Second, we then perform functional analyses in cell and animal models to figure
out how/why the novel genes identified through our genomic studies cause diseases. Right now, our efforts are channeled into
delineating the pathophysiological processes that lead to the formation of blood clots in small vessels of the kidneys of infants
that have mutations in a gene named DGKE. This condition, atypical hemolytic-uremic syndrome, is serious for patients
because most develop renal failure. A better understanding of the disease should help identify potential treatments - currently
there are none.
The student will report directly to me (the PI) and will be working with a Master’s of Science student. It is expected that by end of this project the student will
have achieved the following:
Learn and apply laboratory techniques that relate to endothelial cell biology
Learn and apply laboratory techniques to study lipid biology
Familiarity with using cells generated with CRISPR/Cas9 genome editing techniques
Presentation of data at local events and/or at national/international conferences
Authorship on manuscript (if applicable)
The student will also be required to participate in several academic activities within the Cell Biology Program. These include weekly Journal Clubs, Citywide
Cell Biology seminars and a Cell Biology Trainee Seminar Series (monthly). Also, members of the Lemaire laboratory participate and attend the Division of
Nephrology academic activities, (Journal Clubs/Research Rounds and Citywide Rounds).
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SUPERVISOR: David Cescon / Tak Mak
EMAIL: [email protected]
 FIELD OF RESEARCH: Medical Oncology / Drug Development / Molecular Biology
PROJECT TITLE: Translational Development of Novel Anti-Cancer Drugs
The CFIBCR has developed 2 novel anti-cancer drugs, the first of which is currently under investigation in human Phase I
clinical trials. Ongoing translational work in the laboratory using preclinical cancer models is focused on identifying
biomarkers of sensitivity and resistance as well as potential combination strategies that can be applied in the ongoing clinical
trials of these agents.
A highly motivated student would participate as part of the research team, which includes technicians and post-doctoral
fellows. Student roles would include laboratory experiments (tissue culture, molecular and cell biology techniques), and their
analyses (including bioinformatics and/or pathology, depending on the skills of the student). The student would report to the
lead technician and post-doctoral fellow on a day to day basis, with close supervision from the co-PI (Cescon – clinician
scientist/medical oncologist).
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SUPERVISOR: Andrea Boggild
EMAIL: [email protected]
 FIELD OF RESEARCH: Tropical Medicine; Parasitology; Traveler and Migrant Health
PROJECT TITLE: Towards Diagnostic and Therapeutic Stewardship in Imported Tegumentary Leishmaniasis
Cutaneous leishmaniasis (CL) is an emerging vector-borne disease increasingly imported to North America from the tropics by travelers and migrants. CL can present with a
severe inflammatory phenotype that mimics secondary bacterial infection. Yet, the contribution of bacterial co-pathogens in CL is completely unknown. "Secondarily infected"
ulcers of CL are universally treated with antibiotics, thus, understanding the ulcer microbiome in CL has important implications for antimicrobial stewardship, and evidencebased management strategies.
In addition to possible bacterial co-pathogens in CL, Leishmania RNA virus-1 (LRV1) has been discovered in certain species of Leishmania from Latin America, where
disfiguring mucosal leishmaniasis (ML) is highly endemic. LRV1 is a parasite of a parasite. Again, the contribution of LRV1 to Leishmania infectivity, pathogenesis, and
clinical outcome has been insufficiently explored. If LRV1 does play a role in pathogenesis, there is the potential to harness currently licensed and approved anti-viral drugs in
the fight against CL and ML.
Due to the risk of disfiguring ML following Latin American CL, the WHO advocates for use of highly toxic parenteral drugs such as pentavalent antimony or amphotericin B
for treatment of CL from Latin America. Fluconazole is a safe and well tolerated systemic option for Latin American CL, however, it is difficult to judge a priori if a clinical
strain of Latin American CL will be susceptible to this drug. Thus, surveillance of clinical isolates of Leishmania imported to Ontario for drug susceptibility and resistance
markers will directly inform therapeutic guidelines and stewardship around highly toxic and expensive therapies to which patients with CL need not necessarily be exposed.
The goal of this proposed study is to generate knowledge around Leishmania epidemiology and pathogenesis, and in doing so, influence evidence-based approaches and
guidelines to diagnosis and treatment of cutaneous leishmaniasis (CL) in Canada.
1. Using our existing biobank of surplus Leishmania diagnostic specimens and cultured isolates, we aim to understand the microbiome of CL-ulcers in both inflammatory and
non-inflammatory CL;
2. Using ATCC and clinical strains of Leishmania, we aim to elucidate the role of LRV1 in Leishmania infectivity and clinical phenotype;
3. Using clinical isolates of Leishmania imported to Ontario, we aim to characterize strain susceptibility to fluconazole, and to perform surveillance for inherent and acquired
resistance to anti-leishmania drugs to inform development of an "anti-leishmaniagram".
In order to achieve our aims, we will use a combination of laboratory validation and analytic approaches, including cell culture, end-point and real time PCR, and pyro- and
Sanger sequencing. Our source of Leishmania strains will include the American Type Culture Collection for positive control material, including an LRV1-positive strain of
Leishmania Viannia guyanensis, and surplus, biobanked, delinked clinical isolates.
The student will directly report to Dr. Boggild's current MSc student and RT, as well as participate in regular meetings with the PI. It is expected that the student will contribute
to the following activities over the 20-month period:
Assist with development of an assay for the determination of Leishmania "susceptibility" to fluconazole, which may include in vitro culture work, densitometry, and
Assist with production of an "anti-leishmaniagram" for imported cases of Leishmania to Ontario, which may include real time PCR and sequencing-based experiments;
Assist with generation of a map of the major represented pathogens and non-pathogens in the ulcers of CL, through collation of analyzed next-generation sequencing data;
Assist with in vitro culture, real time PCR, sequencing, and EIA-based experiments related to LRV1 coinfection in leishmaniasis;
Synthesis of results into knowledge products such as abstracts for scientific conferences, or peer-reviewed manuscripts;
Apply for competitive funding awards through scientific program committees for presentation of the work at national and international scientific conferences.
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SUPERVISOR: General Leung / Karen Cross
EMAIL: [email protected] / [email protected]
 FIELD OF RESEARCH: Medical imaging / Wound healing
PROJECT TITLE: Developing New Imaging Devices for Monitoring Wound Outcome
Diabetic patients are 20 times more likely than the general population to be hospitalized with a non-traumatic lower limb amputation. The presence of a diabetic foot
ulcer (DFU) increases this risk by 50%. Currently, there are no accessible, early warning tools or devices that can non-invasively assess tissue health. Consequently,
patients tend to present with late stage disease and saving the limb is very difficult. If we had an early warning tool, we could improve rates of limb salvage, prevent
amputation and reduce morbidity through earlier interventions.
We propose to develop and validate a tool that can assess limb health. We want to measure functional markers, such as tissue oxygenation, perfusion, and free
radical content – because they are important in determining lower extremity tissue health. These markers can be measured using Magnetic resonance imaging (MRI)
non-invasively. While, free radical content is difficult to detect non-invasively in-vivo, the presence of methemoglobin (MetHb) is a surrogate marker of these free
radicals and can be easily detected with MRI. However, despite these findings, MRI still has not received widespread clinical acceptance owing primarily to lack
of availability.
Previously, Dr. Cross has developed a unique camera, called a multispectral imaging device MSID, which can evaluate tissue viability. We hypothesize that
we can measure the above parameters with this tool, and are important in evaluating the tissue health of the diabetic lower extremity. Changes in these parameters, as
measured with the MSID, would serve as an early warning tool of tissue compromise before the presentation of clinical symptoms.
The specific aim of this study is to assess utility of MSID for characterization of tissue physiology of the lower extremity in diabetic patients with and without
lower extremity wounds. We will correlate and correct our findings of MSID to those found in MRI, which we use as our gold standard. This project will give the
student exposure to MRI as well as multispectral optical imaging. Further, the student will get exposure to image processing and be at the edge of the clinical / research
environment interacting with both scientists and researchers.
Dr. Cross is a surgeon scientist working at St Michael’s Hospital and has been developing the multispectral imaging device for applications in burn wounds.
Dr. Leung is an MRI Physicist at St Michael’s Hospital and has been developing techniques to measure metHb. Together, these two new scientists are trying to develop
new technology with exciting potential to change the way these patients are managed and treated.
Students will be responsible for talking with patients and discussing their comfort in participating in this study. They will interact with patients through the entire
process while the patients are recruited in this study, ensuring they get to MRI and then operating the multispectral imaging device. Students will interface with
imaging technologists, and nursing staff as well as with the other students working in the lab.
Students will get the opportunity to work with advanced image processing software (e.g. Matlab), and if desired, develop and modify these algorithms to
optimize detection of the imaging biomarkers. This project is co-supervised by both Dr. Cross & Leung and the student will report directly to these two, with
weekly lab meetings.
As both Dr. Cross & Leung are new scientists, this is a young and dynamic group with a large opportunity to take on as much responsibility and direction of this
project as the student is able.
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SUPERVISOR: Natalie Coburn
EMAIL: [email protected]
 FIELD OF RESEARCH: Evaluating and improving surgery outcomes for gastrointestinal malignancies
PROJECT TITLE: Survival, treatment and identifying predictors of receipt of adjuvant therapy for curative pancreatic
adenocarcinoma: a population-based analysis
According to Canadian Cancer Statistics, pancreatic cancer ranks 12th in terms of the number of new cases diagnosed in 2012, however, as most
patients die of this disease, it represents the 4th most common cause of cancer-related deaths. In 1889, surgeons described resection of lesions in
the tail of the pancreas, and in 1935, Allen Whipple described a technique for resection of pancreas cancers within the head of the pancreas. Little
has changed in over one hundred years, with these resections representing the only way to cure pancreas cancer. Over the past several decades,
data has emerged to suggest that chemotherapy or chemoradiation, following a curative resection may improve the survival of patients with
pancreas cancer. However, these therapies have only been examined in randomized control trials, and the efficacy of these treatments, when
applied to a population of patients has not been examined. Physicians still question whether chemotherapy, or chemoradiation is the best treatment
option. For our project, Survival, treatment patterns, and identifying predictors of receipt of adjuvant therapy for curative pancreatic
adenocarcinoma: a population-based analysis, our objectives are to:
1. Define survival for curatively resected pancreatic adenocarcinoma on a population-level,
2. Identify independent predictors of survival for all patients with curatively resected pancreatic adenocarcinoma,
3. Identify independent predictors of adjuvant chemotherapy or chemoradiation versus no additional therapy.
The student’s role depends on the progress of our projects, however will likely include conducting chart reviews, summarizing existing literature,
assessment of treatment costs, as well as analysis of data output and manuscript preparation. The student will report to Dr. Natalie Coburn, who is
the PI of the listed projects. The student will also have support available from other team members, including Masters students and research
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SUPERVISOR: Natalie Coburn
EMAIL: [email protected]
 FIELD OF RESEARCH: Evaluating and improving surgery outcomes for gastrointestinal malignancies
PROJECT TITLE: A population-based outcome and economic evaluation of interventions for gastric cancer
Adenocarcinoma of the stomach, or gastric cancer (GC) is also a highly fatal disease in Canada, and one of the most costly to treat. Although
tremendous advances in the treatment of GC have been made, most have occurred in just the past decade. While promising results have been
shown in published studies, real-world clinical outcomes and costs have not been assessed. In our previous work, we assembled a cohort of 2516
patients diagnosed with GC, and collected complete staging data for these patients through an extensive provincial chart review. We have also
linked this to a large database of clinical and staging information with administrative data on outcomes, resource utilization and costs. For our
project, A population-based outcome and economic evaluation of interventions for gastric cancer, our objectives are to:
1. Compare the clinical outcomes of Ontario GC patients who received one of the competing treatment strategies in the clinical scenarios of
laparoscopic versus open resection, and chemotherapy vs chemoradiation,
2. Describe the resource utilization and costs of managing GC patients in Ontario by surgical and adjuvant treatment strategy,
3. Conduct cost-effectiveness analyses for laparoscopic versus open resection, and chemotherapy versus chemoradiation.
Our research leverages administrative datasets to examine these topics in retrospective cohorts of patients treated for gastric and pancreatic cancers.
We utilize data obtained through chart reviews, and in collaboration with the Institute for Clinical Evaluative Sciences, to determine predictors of
survival, receipt of therapy, as well as to examine any potential barriers towards receipt of optimal care. Our multidisciplinary research team
consists of gastrointestinal surgeons, clinical epidemiologists, health economists, and statisticians.
The student’s role depends on the progress of our projects, however will likely include conducting chart reviews, summarizing existing literature, assessment of
treatment costs, as well as analysis of data output and manuscript preparation. The student will report to Dr. Natalie Coburn, who is the PI of the listed projects.
The student will also have support available from other team members, including Masters students and research assistants.
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SUPERVISOR: Michael J. Kutryk
EMAIL: [email protected]
 FIELD OF RESEARCH: Stem cells, interventional cardiology, biomedical engineering
PROJECT TITLE: Oriented antibody coating on ePTFE grafts to promote endothelialization
From concept, to bench testing, and animal implants, the first bioengineered coronary stent was developed in my laboratory. Using polymeric dextran to
immobilize anti-CD34 antibodies, the device captures circulating endothelial progenitor cells (EPCs) in vivo, and facilitates the rapid establishment of a healthy,
confluent endothelialium on the surface of the treated arterial segment rendering it non-thrombotic. The first human implant in North America was performed at
St. Michael’s Hospital in 2006, and the device is now sold world-wide as the Genous™ stent.
The EPC-capture coating technology has applications for other clinically relevant synthetic materials such as expanded polytetrafluoroethylene (ePTFE), the
most frequently used material for vascular grafts. The use of synthetic grafts for the treatment of PAD is limited by the failure of the ePTFE to completely
endothelialize in humans, resulting in continued thrombo-inflammatory events on the surface. The high flow rates of large diameter vascular grafts provide
long-term (>10 year) patency rates of 85-95% with only minimal adjunctive pharmacological therapy however, the successful development of small-diameter
artificial vascular prostheses (<5 mm) continues to be a challenge due to the shortened patency caused primarily by the high thrombogenicity of ePTFE. In fact,
less than 50% of small diameter femoral-popliteal grafts remain patent 5 years post-implantation. Although the EPC capture technology has great potential to
address this problem, we found that the dextran antibody immobilization technique was not effective on ePTFE.
In our efforts to passivate the surface of ePTFE with healthy endothelium by the in vivo capture of EPCs, we have developed a binding technology that is able to
immobilize not only antibodies, but a myriad of biomolecules on virtually any substrate. This improved binding technology can be applied to other intravascular
devices, for purposes other than EPC capture, and has applications beyond implantable medical devices as well. Characterization of our novel coating on ePTFE
will be performed by assessing the coating thickness, coating homogeneity, confluence and barrier effectiveness. Techniques such as fluorescence microscopy,
contact profilometry and scanning electron microscopy will be used for characterization. In vitro CD34+ cell binding assays will be performed to examine the
efficacy of coated ePTFE graft material, and ultimately in vivo assessments in both rabbit and pig animal models will be undertaken. We have extensive
experience in the development and assessment of novel implantable intravascular devices, and the expertise and resources in my laboratory necessary for the
successful completion of this project.
The student will be involved in the coating of ePTFE, and the characterization of the coated surface. The student will be responsible for obtaining
fluorescence and scanning electron microscopic images of the active surfaces and will perform cell binding assays and assist with pre-clinical
animal testing. The student will be under the supervision of a senior research associate in my laboratory and will directly report to me, the principle
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SUPERVISOR: Marc Jeschke / Saeid Amini Nik
EMAIL: [email protected] / [email protected]
 FIELD OF RESEARCH: Stem cell research / Skin healing and skin regeneration
PROJECT TITLE: Interaction between myeloid cells and mesenchymal stem cells during (ab)normal healing
We have preliminary data that shows the secretome of myeloid cells affect mesenchymal stem cells behaviors. This effect has role in normal skin
healing and might have role in pathogenesis of some fibro-proliferative disorders like Keloids. Using different in vitro and in vivo techniques, we
evaluate this interaction and will examine how myeloid cells modulation will impact on Keloids’ behaviors.
The lesson learned from this project will not only provide some potential remedies for management of keloids in patients but also provide insights
in the mechanism of rejuvenating stem cells in elderly.
Applicant should be familiar and comfortable with cell culturing, western blotting and immunohistochemistry.
Being familiar with confocal imaging and flow cytometry analysis is not a must but ideal.
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SUPERVISOR: Marc Jeschke / Saeid Amini Nik
EMAIL: [email protected] / [email protected]
 FIELD OF RESEARCH: Stem cell research / Skin healing and skin regeneration
PROJECT TITLE: Regenerating Skin for Burn Patients
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.
The current project 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 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 research fellows, 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.
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SUPERVISOR: Marc Jeschke
EMAIL: [email protected]
 FIELD OF RESEARCH: Metabolism; Burns; Immunology; Cell Regeneration
PROJECT TITLE: Deciphering the mitochondrial response to severe burn injury: Toward a comprehensive understanding of
patient hypermetabolism
The research project outlined herein will seek to uncover the function of mitochondria in the initiation and progression of the hypermetabolic response following severe burn
injury. This phenomenon, a ubiquitous reaction to burn trauma, is associated with systemic catabolism. The latter involves protein breakdown in all tissues, a process which
gives way to multiorgan dysfunction. As hypermetabolism is linked to this failure and the pathogenesis of severe infection and sepsis, alleviation of this burn response would
greatly ameliorate burn care protocols.
Mitochondria are, to date, a poorly understood subcellular organelle with regards to the postburn hypermetabolic response. Key functions undertaken by
mitochondria include bioenergetics (adenosine triphosphate synthesis and storage), antioxidant synthesis (alpha-keto acid production via the tricarboxylic acid cycle), lipid
homeostasis (breakdown by beta-oxidation) and control of cell death (apoptosis). A comprehensive understanding of these processes may unearth hitherto unknown treatments
which modulate hypermetabolism to limit patient morbidity and mortality.
Possible research streams include:
Lipogenesis: The modulation of enzymes involved in lipid production, such as acetyl-CoA carboxylase and acetyl-CoA synthetase, as well as the production of
raw substrates for lipid biosynthesis, particularly in adipose tissue, can further increase our comprehension of dyslipidemia in burn patients.
L-carnitine homeostasis: This non-standard amino acid plays a key role in lipid transport to the mitochondria for breakdown. Diminished synthesis of this
biomolecule has been associated with impaired fatty acid metabolism and lipogenesis. Assessment of carnitine levels and synthetic pathways may further the
understanding of postburn lipolysis.
Keto-acid metabolism: The mictochondria houses the citric acid cycle, a series of enzymatic reactions aimed at the generation of reducing factors for ATP
production. Mitochondria-targeted metabolites such as pyruvate, 2-oxoglutarate and oxaloacetate can act as potent antioxidants in situ. As severe burns lead to
increased oxidative stress, the activity of enzymes mediating the homeostasis of these organic acids may aid in the understanding of defensive systems in
affected tissue.
The data gleaned from these studies should greatly advance our knowledge of postburn metabolism, with the ultimate goal being the informed development of better short- and
long-term therapies for severe burn injuries.
The student will be responsible for acquiring and processing data from experiments using various biochemical techniques. These include, but are
not limited to, pipetting, preparing buffers, electrophoresis, cell culturing and fluorescence microscopy. He/she will be directly supervised by Dr.
Christopher Auger (PDF), and will report research progress to him on a weekly basis. The student is expected to perform his/her duties in a
responsible and timely fashion, while adhering strictly to ethical research guidelines.
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SUPERVISOR: Kenneth Croitoru
EMAIL: kc[email protected]
 FIELD OF RESEARCH: Gastroenterology, Mucosal Immunology, IBD
PROJECT TITLE: Understanding the role of T cell-intrinsic Nod2 via generation of a T cell-specified Nod2 knockout mouse
The intestinal mucosa is exposed to a large number and variety of commensal microorganisms. In pathological conditions such as inflammatory bowel diseases
(IBDs), an abnormal immune response towards commensal bacteria can contribute to mucosal inflammation. Indeed, Crohn’s disease (CD) is characterized by
activation of T cells that produce inflammatory cytokines and contribute to intestinal inflammation and mucosal barrier destruction. This abnormal inflammatory
response is thought to result from the effect of environmental or microbial activation of the local immune response in a genetically predisposed host.
Host factors that serve to exclude microorganisms from the gut mucosa include those involved in the maintenance of the barrier function of the intestinal
epithelium, and those involved in the regulation of the innate and adaptive immune response to bacterial triggers. Some of the genes involved in these pathways
are among the genetic variants identified as risk alleles associated with CD, including genes involved in innate sensing of bacteria such as Nod2. Nod2 was the
first gene to be associated with Crohn's disease, and it remains one of the genetic risk factors that confers the greatest risk for the development of Crohn's
disease. Nod2 detects muramyl dipeptide (MDP) that is ubiquitously present in bacterial peptidoglycan and is crucial for innate immune responses to certain
bacterial infections.
We have previously shown that Nod2 is expressed in T cells and is inducible upon T cell activation (Zanello, 2013, PLOS One). More recently, we have
identified a delayed epithelial recovery in Nod2-deficient mice following T cell-driven mucosal damage. The main goal of this project will be to understand the
role of T cell intrinsic Nod2 in T cell function during colitis.
In Aim 1, the student will be responsible for the generation of a T cell-specific Nod2 knockout mouse. Using the Cre-Lox recombination system, the student
will cross Nod2-flox mice with mice expressing Cre under the control of Lck (lymphocyte protein tyrosine kinase) promoter, resulting in the deletion of Nod2
specifically in T cells. The student will be responsible for maintenance of the colony, including weaning pups, genotyping and monitoring health status. Since
the microbiome has a profound influence on the immune system, the student will also be responsible for examining the gut microbiota of the colony, through
16S ribosomal RNA analysis on stool samples, over time.
In Aim 2, the student will assess the influence of T-cell specific deletion of Nod2 in a model of colitis. A sing intra-peritoneal injection of anti-CD3 will be
used to induce acute T cell-driven mucosal damage. The student will then evaluate the response using the following techniques: histological analysis of the small
intestine, measurement of key cytokines in the small intestine via ELISA, and quantitative PCR analysis of mRNA profiles of the damaged mucosa.
These experiments will help define the T cell-intrinsic role of Nod2 in mucosal healing. As such, the data will provide valuable insight into understanding how
Nod2 mutations could set the stage for altered T cell function in the development of IBD.
In Aim 1, the student will be responsible for the generation and maintenance of the Nod2-flox x Lck-cre mouse colony. This will include weaning pups, genotyping, and
monitoring the health status (ie. weight) of the mice. The student will receive the required animal handling training in order to work with research animals. Once the colony has
been generated, the student will be involved in evaluating the microbiota community structure of the mice. As such, the student will collect stool weekly for bacterial DNA
extraction. The student will perform the collection, DNA isolation from stool and quantitative PCR to determine the bacterial community structure. The protocols for all
procedures that the student will perform are well established in the lab.
For Aim 2, the student will work in collaboration with Dr. Galliano Zanello (PDF) and Ashleigh Goethel (PhD candidate) for the in vivo anti-CD3 model. The student will assist
with the above-mentioned analysis, including ELISA for cytokines and qPCR for mRNA profiles.
The student will be supported by both Dr. Galliano Zanello (PDF) and Ashleigh Goethel (PhD candidate) and will report directly to Ashleigh. Weekly lab meetings with Dr.
Croitoru will provide a venue for discussion of experimental results and future directions.
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SUPERVISOR: Michael Fehlings
EMAIL: [email protected]
 FIELD OF RESEARCH: Spinal cord injury, stem cells, regenerative medicine
PROJECT TITLE: Investigation and Treatment of Traumatic Axonal Dysfunction after Spinal Cord Injury
CIHR-funded studies by our team have shown that axonal demyelination at the site of spinal cord injury (SCI) results in axonal dysfunction and functional
neurological deficits. We were among the first to show that transplanted adult neural precursor cells (NPCs) can remyelinate spinal cord axons and enhance
functional recovery after thoracic SCI and in congenitally dysmyelinated Shiverer (shi) mice lacking myelin basic protein (MBP). Furthermore, we have
targeted the glial scar with chondroitinase ABC (ChABC), allowing for successful use of NPCs in a model of chronic thoracic SCI, where we were able to
reduce axonal dieback, facilitate remyelination, induce synaptic plasticity and promote neurobehavioral recovery. Importantly, we have novel data that
transplantation of NPCs following cervical SCI also leads to increases in forelimb function, a finding of considerable mechanistic and translational significance.
Moreover, our data suggest that NPCs may affect multiple mechanisms of repair and that recovery and could be dependent on the level of transplantation. While
plasticity may contribute to functional recovery in cervical SCI, mechanistic insight into stem cell-based plasticity is still limited. Although initial efforts are
underway to apply cellular therapies in patients, the clinical translation of stem cells for SCI is critically limited by factors including: (i) a lack of studies in
cervical SCI, (ii) uncertainty as to the mechanisms by which NPCs promote repair, (iii) how these mechanisms can be enhanced, and (iv) ethical issues
surrounding the source of NPCs. We intend to address these critical gaps in the proposed studies by: (i) applying a novel model of cervical SCI, (ii) delineating
the contributions of remyelination and plasticity to functional recovery, (iii) using bioengineered biologics to enhance remyelination and plasticity, and (iv)
transplantation of clinically relevant induced pluripotent stem (iPS) cell-derived NPCs. This work will build on our promising results and will address key
knowledge gaps in the field by employing novel techniques – with the goal of uncovering critical mechanisms relevant to the feasibility of clinical translation.
Overarching hypothesis: Transplantation of NPCs into the injured cervical cord promotes neurobehavioural recovery through mechanisms of remyelination and
plasticity, which can be exploited by environmental modification to further improve recovery.
The student will work closely with and report to a PDF/Scientific Associate in the Fehlings Lab. The student will learn about models of spinal cord injury,
microsurgical implantation of neural stem cells and neuroanatomical, neurophysiological and neurobehavioural assessments. His/her responsibilities will
include tissue processing, immunostaining molecular (DNA/protein) assays and data analysis.
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.
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SUPERVISOR: Michael Fehlings
EMAIL: [email protected]
 FIELD OF RESEARCH: Spinal cord injury, stem cells, regenerative medicine
PROJECT TITLE: Mechanistic insights and neuroprotective approaches to enhance recovery in age related degenerative
spinal cord injury
Cervical spondylotic myelopathy (CSM) is a progressive neurodegenerative disease of aging wherein the cervical spinal cord is slowly compressed due to age
related degenerative changes in the spine. The extrinsic cord compression causes gradual flattening of the intrinsic transverse vessels or terminal branches of the
anterior spinal artery resulting in reduced blood flow and ischemia. This causes extensive gray matter damage and demyelination in ascending and descending
tracts leading to gait disturbances, hand dysfunction and pyramidal and posterior column deficits. CSM is the most common form of spinal cord impairment in
the world and almost exclusively occurs in the elderly – severely reducing independence and quality of life. Despite advances in decompressive surgery, many
patients are left with substantial neurological disability; hence, there is considerable need to identify novel therapeutic targets which could complement or
substitute for existing surgical treatments. In order for effective therapies to be developed, critical gaps in our knowledge of the pathobiology of CSM need to be
Our laboratory, one of the few in the world that studies CSM, has made important insights into the pathology of CSM through development of animal models
and our unique access to human pathological specimens. In a recent publication, we showed that inflammation contributes to the pathobiology of spinal cord
degeneration in human cervical CSM and in a complementary murine model of this condition. Based on strong preliminary evidence for the involvement of
chronic ischemia, vascular damage, blood-spinal cord barrier dysfunction and neuroinflammation in the pathogenesis of neural degeneration in CSM, we will
address novel mechanistic questions related to these therapeutic targets. In particular, this study will focus on the endothelial cell PPARδ-miR-15a axis and
macrophage/microglial CX3CR1 mediated inflammation. Importantly, evidence points to these factors being relevant to aging and our preliminary data
demonstrate that they are key mechanisms of disease in CSM.
The CREMS student will work closely with and report directly to a senior trainee or PDF in the Fehlings Lab. The student will learn about models of cervical
spondylotic myelopathy, microsurgical techniques and neuroanatomical, neurophysiological and neurobehavioural assessments. His/her responsibilities will
include tissue processing, immunostaining molecular (DNA/protein) assays and data analysis.
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/CSM through exposure to a
variety of essentials research techniques and methods in molecular biology, behavioral study and microsurgery.
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SUPERVISOR: Theodore J. Brown
EMAIL: [email protected]
 FIELD OF RESEARCH: Ovarian cancer, Reproductive Biology
PROJECT TITLE: Clinical and Immunological Importance of Lymph Node involvement in Advanced Stage Epithelial
Ovarian Cancer
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer-related death in developed countries, with nearly a quarter
million women diagnosed worldwide annually. It is typically diagnosed at an advanced stage with the peritoneal cavity being the most frequently
involved site; however, involvement of other distant metastatic sites such as the liver, chest, pleura and retroperitoneum is common. EOC typically
spreads transcoelomically, but lymphatic and hematogenous spread may explain involvement of extra peritoneal disease that is found in many
patients. A combination of surgery and chemotherapy is required to treat advanced stage ovarian cancer. Despite good initial treatment results,
and the ability to achieve a remission in many cases, most patients will experience a recurrence of their disease and cure rates are low.
It has long been established that EOC can stimulate a host immune response, and that the presence of tumor infiltrating T cells, particularly
CD8+ cytotoxic T cells (CTL), is associated with a better outcome. Currently, the stimulus that leads to the presence of tumor infiltrating
lymphocytes in some patients, and the absence of these cells in other patients is not well defined. Furthermore the source of these cells is
unknown. Based on knowledge derived from other solid tumors, it is reasonable to assume that antigen-presenting cells exposed to different cancer
epitopes, lead to stimulation of immune cells and activation of regional lymph nodes. Currently, the data on the contribution of lymph nodes to the
immune response in advanced ovarian cancer is lacking. The impact of positive lymph nodes on the immunological and clinical outcome of
advanced ovarian cancer is also unknown. The objective of this study will be to assess the clinical and immunological significance of lymph node
involvement in stage 3-4 EOC.
Aim 1: To compare clinical outcomes such as progression free survival, overall survival, outcome of surgery and volume of ascites between
patients with positive vs negative lymph nodes based on assessment at the time of primary surgery.
Aim 2: To determine if between BRCA1 and BRCA2 mutation status and lymph node involvement are correlated in advanced stage EOC.
Aim 3: To characterize the immune cell population in positive and negative lymph nodes in advanced stage EOC, and compare it to the
population of immune cells infiltrating the primary tumor within the same patient.
Our project will involve clinical data collection and analysis (at Credit Valley Hospital) and a basic science component that will be done in Dr.
Brown’s laboratory. We have a multi-disciplinary team including a pathologist to support the student in the project starting from the conception of
the study to its successful completion
The student will be involved with all aspects of the research including submission of REB, data collection and data analysis. The student will be supported by a gynecologic
oncologist at an active cancer center and a statistician.
The student will participate in selecting and gathering of appropriate histologic specimen under the supervision of a gynecologic pathologist.
The student will participate in performing lymph node assessment by ways of flow cytometry and immunohistochemistry under the supervision of a Scientific Associate in the
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EMAIL: [email protected]
 FIELD OF RESEARCH: Cardiovascular Outcomes and Health Services Research
PROJECT TITLE: The CANHEART Study: Using big data to transform the prevention and management of cardiovascular
The CANHEART project is a unique, population-based observational research initiative aimed at measuring and improving cardiovascular health and the quality
of ambulatory cardiovascular care provided in Ontario, Canada. The strength of this project lies in the large sample size and diversity of the databases that are
linked together. Currently, 17 different routinely collected data sources have been linked to create the CANHEART cohort, containing information on 9.8
million Ontarians age 20-105 years from 2008.
Leveraging this dataset, the student’s project will study various factors in the relationship between patient, community and health system factors, and
cardiovascular health outcomes. Although previous literature has found an association between socioeconomic status and cardiovascular health outcomes, there
is limited comprehensive information on the specific determinants (i.e. variation in health care access, cardiovascular risk factor management, and medication
adherence) that contribute to differences in the cardiovascular health outcomes among different populations. Using the large population-based CANHEART
cohort, the student will perform secondary analyses to determine whether there are significant differences between various sub-populations (e.g. by sociodemographic factors) in health care utilization and cardiovascular risk factor management and control (e.g. of diabetes, hypertension, hypercholesterolemia) that
may contribute to disparities in cardiovascular health outcomes.
Results from this study of cardiovascular disease in a diverse multi-ethnic population will help identify gaps in preventative health care, identify specific
sociodemographic groups at increased cardiovascular risk, and could potentially inform the development of much more effective prevention practices and
policies to significantly reduce disparities in cardiovascular outcomes of Ontarians.
For more information about the CANHEART study, please see or follow the project on Twitter @CANHEART_news.
With the study Principal Investigator as his/her direct report, as well as with guidance from an Epidemiologist and other study team members, the student will be
responsible for: 1) performing a literature review pertaining to the research topic, 2) developing and documenting study analytic methodologies, 3) working with
a Research Analyst to conduct the data analysis on a subset of the existing CANHEART database and interpret results, and 4) preparing an abstract and/or
manuscript to share research findings with the academic community. Due to the project’s high use of quantitative data and analytic methods, preference will be
given to students with background or training in epidemiology or biostatistics.
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SUPERVISOR: Samira Mubareka
EMAIL: [email protected]
PROJECT TITLE: Characterization of aerosol-producing procedures using a human simulation model
Summary: Healthcare workers (HCWs) are frequently exposed to nefarious human pathogens. There are protocols and procedures in place to mitigate the spread of well-known infectious
diseases from patients to HCWs. However, insight into the dispersion of emerging and re-emerging pathogens is lacking, and continues to be a pressing issue for certain seasonal & endemic
pathogens such as human influenza viruses, as well as novel agents such as the Middle East Respiratory Syndrome Coronavirus (MERS CoV), influenza viruses of avian origin and Ebola virus.
Aerosol-generating procedures such as intubation are an essential aspect of patient care, particularly during acute respiratory illness, but have also been implicated in the transmission of respiratory
pathogens, including SARS. There is a dearth of empiric data regarding which procedures generate aerosols, and under what circumstances.
Aims: To empirically determine which procedures generate aerosols and identify high risk situations. Our goals also include providing cross-disciplinary training for highly-qualified personnel
and rapprochement through collaboration between individuals from stakeholder disciplines including nursing, respiratory therapy, critical care, infectious diseases, occupational health,
occupational hygiene, biophysics, and virology.
Approach: We propose a three-pronged approach whereby particle counts during aerosol-generating procedures will be determined in 3 settings: a) simulation, using a human patient simulation
system, b) comparative, using an animal (porcine) model, and c) clinical, where measurements will be taken during elective and emergency patient aerosol-generating procedures. Determinants for
aerosol-generation will be sought. Work in the simulation centre, would be scheduled and predictable. Thus, we propose the CREMS student take on this aspect of the project. In brief:
Year 1: Using the patient simulator, high speed video images will be used to guide location of Aerotrak (handheld optical particle counter) measurements for the following procedures and
maneuvers: chest compressions, bagging, tracheal intubation and extubation, endotracheal aspiration, ventilator disconnection, non-invasive positive pressure ventilation and other forms of
exogenous oxygen delivery. The ventilation system in the simulation suite has an integrated vane system which permits control of the direction of airflow in order to simulate various ventilation
scenarios. Each putative aerosol-generating procedure will be tested without ventilation, and with at least 3 different ventilation scenarios (determined based on the likely setting for each
Year 2: We have access to a facility at Western which we built in collaboration with E. Savory, a fluid dynamics engineer. Termed the FLUGIE, the system consists of a sizable enclosure designed
to enable particle imaging velocimetry (PIV). This system will can generate velocity fields from aerosols. This will tell us the speed and direction of particles, providing additional insight into the
ultimate fate of these particles. In addition, we can aerosolize phi6 bacteriophage (a virus that infects plant bacteria and is harmless to humans); it is a single-stranded enveloped RNA virus like
influenza and many other respiratory viruses and thus a safe but representative model. We can use our viral aerosol sampling equipment within the FLUGIE to determine the dispersion of the
virus. Because of the use of lasers for PIV, this work will be limited to modes of ventilation, and not procedures requiring an operator inside the chamber for PIV measurements.
While the CREMS student would have the opportunity to participate in porcine model and clinical sampling trials, these are already ongoing (MSc student) and are also much
less amenable to sporadic participation throughout the year (must be available on very short notice). Further to the general outline of this aim, the student would be expected to
1. An in-depth review of the literature
2. Protocol development
3. Experimental design
4. Experimental execution
5. Data collection and analysis
6. Dissemination
Day-to-day operations are overseen by our technicians, and both MSc students and a post-doctoral fellow are available for assistance trouble-shooting. The student will be
expected to generate quarterly reports and attend and present at lab meeting (quarterly). They will report to me on a monthly basis, weekly over the summer when they will have
the opportunity to assist with porcine model and clinical sampling. By virtue of being in our lab, the student will also acquire skills in biosafety and infection prevention and
control. The student will present at LMP and SRI summer student poster days and we anticipate one potential conference abstract and one peer-reviewed publication will be
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SUPERVISOR: Daniel Mueller
EMAIL: [email protected]
 FIELD OF RESEARCH: Genetics, Pharmacogenetics, gut microbiome
PROJECT TITLE: The role of the gut microbiome in schizophrenia and antipsychotic-induced metabolic side effects
1. Introduction. Metabolic abnormalities, obesity, and cardiovascular diseases are a leading cause of premature death in schizophrenia (SCZ) patients being
treated with antipsychotic (AP) medications. Significant antipsychotic-induced weight gain (AIWG) is observed in more than 30% of SCZ patients and is the
major cause of increased obesity rates in the SCZ population. Patients treated with APs show increased glucose tolerance, insulin resistance (IR), weight gain
and hyperphagia.
More recently, the gut microbiome (GMB) has been described to play a key role in weight and metabolic regulation, and has been implicated in obesity and in
AP-induced abnormalities. Reduced or disturbed microbial diversity may lead to excess adiposity and metabolic dysregulation mediated by differential abilities
of specific bacterial species to salvage energy and produce substrate to regulate the metabolism. This research proposal aims to identify the role of the GMB in
antipsychotic-induced metabolic changes and AIWG in participants with SCZ. In addition, the GMB has also been implicated to possibly modulate the onset of
SCZ and thus we will also compare the GMB of SCZ patients with healthy controls.
2. Objectives and Hypotheses. My objectives are 1) to compare the GMB of SCZ patients with healthy controls once at baseline and 2) follow SCZ patients
three and six weeks after starting or switching to an AP. We will investigate whether (i) alterations in the GMB are associated with altered food intake, weight
change, and glucose levels, and (ii) if specific microbial signatures are associated with these metabolic changes. I hypothesize that in patients with SCZ,
alterations across taxonomic ranks will be altered from baseline levels (day 0) and up to six weeks after exposure to AP treatment. I also expect that a switch to
AP treatment will adversely alter patient metabolic phenotype. Relative to the control group, we expect the GMB of AP-treated patients to have an increased
abundance of Firmicutes and taxa associated with obesity. This will represent the first human study of GMB changes in relation to AP treatment and its
associated metabolic side-effects.
3. Project Plan.
In total, we will collect 100 fecal samples (25 control samples and 25 SCZ patient samples at each baseline, week 3 and 6) for GMB analyses using OMNIgeneGUT OMR-200 feces self-collection kits (DNA Genotek, Kanata, ON). For GMB analysis (mainly performed by DNAGenotek), fecal DNA will be extracted
following Human Microbiome Project (HMP) extraction guidelines (HMP-07-001). Sequencing will be performed on an Illumina MiSeq®16S Sequencing
Platform. Microbial community abundance and diversity will be characterized by sequencing 16S-rRNA genes from fecal DNA. We will use pipeline
procedures acknowledged by the HMP, namely the mothur and QIIME software packages.
4. Context and Relevance. To the best of my knowledge, this is the first investigation that attempts to create a link between changes in the GMB and SCZ,
AIWG and AP-induced metabolic abnormalities in a human patient population.
The designated medical student will obtain the opportunity to assist in the coordination and execution of this project, including data analyses,
conference presentation and article submission. I will serve as direct report to the student.
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SUPERVISOR: Z. J. Daskalakis
EMAIL: [email protected]
 FIELD OF RESEARCH: Neurophysiology of severe psychiatric disorders
PROJECT TITLE: Brain stimulation in Depression
The specific aims of this proposal are: (1) to conduct a randomized non-inferiority trial evaluating the efficacy of two different forms of repetitive transcranial
magnetic stimulation (rTMS) for treatment resistant depression (TRD) and (2) to identify biomarkers of rTMS treatment response. The two form of rTMS being
compared are conventional high frequency rTMS (HF-rTMS) and a novel form of rTMS that is referred to as intermittent theta burst stimulation (iTBS). iTBS
can be administered in 1/10th of the time of HF-rTMS (~3 min vs. 37.5 min) yet achieves similar or greater effects on neural plasticity. Both forms of rTMS
treatment are applied over the left dorsolateral prefrontal cortex (DLPFC) through MRI-guided neuronavigation. Our pilot data (i.e., N=33) demonstrates strong
evidence for non-inferiority between HF-rTMS and iTBS. As iTBS is a much shorter treatment compared to the HF-rTMS, our findings could achieve
substantial improvements in both clinical capacity and treatment cost, by allowing 8-10 times as many patients to be treated per hour without requiring any
additional equipment or staff. Identifying biomarkers of rTMS treatment response could further improve treatment efficiency and efficacy by identifying the
patients hwo are most likely to respond to rTMS treatment. As part of our clinical trial, therefore, we will collect a multimodal suite of biological measures (i.e.,
neuroimaign, neurophysiological, molecular) to train machine-leaning algorithms for robust, individual-patient outcome prediction. Overall, this proposal will
have substantial real-world impact by improving the time and cost-effectiveness of rTMS – one of the few established treatments in TRD – and by developing
the fisrt reliable biomarkers to guide rTMS treatment selection in individual patients with TRD.
Clinical evaluation
Treatment exposure
Neurophysiology testing
Director report will be post-doctoral fellow and/or scientist
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