1.
If you are interested in working with one of these supervisors on the project outlined, contact the supervisor to arrange a meeting with them to discuss further;
2.
If an agreement is made between you and the supervisor to work together, the supervisor must complete the
Mentor Agreement Form (found on CREMS website) and send via email to Lisa Charrette, CREMS
Coordinator at crems.programs@utoronto.ca
by end of day November 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.
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EMAIL: macdonald@smh.ca

PROJECT DESCRIPTION:
The goals of our laboratory are to define the cellular and molecular mechanisms that cause angiographic vasospasm, microvascular injury and poor outcome after subarachnoid hemorrhage. The approach is translational and uses techniques ranging from animal surgery, molecular biology (PCR, Western blotting), immunohistochemistry to confocal imaging, microscopy and electrophysiology and focuses on mechanisms of brain injury after subarachnoid hemorrhage. We are studying how blood clot contracts cerebral arteries and how to prevent it. 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 ROLES & RESPONSIBILITIES

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
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EMAIL: jennifer.jones@uhn.ca

PROJECT DESCRIPTION:
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 (www.ellicsr.ca), 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) post- intervention. The results of this pilot study will be used to inform the development of a larger randomized control trial.
STUDENT ROLES & RESPONSIBILITIES

Student will work closely with Drs. Jones and Ferguson and the research and clinical tem at
ELLICSR ( http://ellicsr.ca/ ) 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
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EMAIL: fischerc@smh.ca

PROJECT DESCRIPTION:
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 ROLES & RESPONSIBILITIES

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 assistant
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EMAIL: kirpalania@smh.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES

Data collection

Data Analysis and Statistical Analysis

Literature Review

Scientific Writing of Abstract and Manuscript
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EMAIL: jkingdom@mtsinai.on.ca

PROJECT DESCRIPTION:
T Severe pre-eclampsia is a placenta mediated disorder characterized by hypertension, vascular injury and multi-organ dysfunction in the 3 rd trimester. The disease becomes established during the 2 nd trimester, and presents in the 3 rd 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 2 nd trimester. Our in-vivo studies in the 2 nd 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 2 nd 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.
STUDENT ROLES & RESPONSIBILITIES

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
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
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
EMAIL:
Benjamin.goldstein@sunnybrook.ca

PROJECT DESCRIPTION:
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: http://sunnybrook.ca/content/?page=bsp-youth-bipolar-disorder-research
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.
STUDENT ROLES & RESPONSIBILITIES

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 postdoctoral 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
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EMAIL: adam.shilen@sickkids.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
 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
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EMAIL:
Yvonne.bombard@utoronto.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES

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,
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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)
EMAIL: mkoritzi@uhnresearch.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
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
Supervised directly by PI. A research associate will aid in training of lab techniques and an animal technician will provide support for in vivo experiments

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
EMAIL: wendy.levinson@utoronto.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
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: http://www.abimfoundation.org/Initiatives/Putting-
Stewardship-into-Medical-Education-and-Training-Grant.aspx
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EMAIL: ohjiw@smh.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES

Acquire an understanding of clinical research methodology (patient recruitment, research ethics, obtaining informed consent, study visit protocols, data collection and extraction).
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
To acquire an understanding of and apply principles of data acquisition and analysis in imagingbased 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
EMAIL: lorraine.kalia@utoronto.ca

PROJECT DESCRIPTION:
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-sci entist 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-ofthe-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.
STUDENT ROLES & RESPONSIBILITIES



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
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
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)
EMAIL: istvan.mucsi@utoronto.ca

PROJECT DESCRIPTION:
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
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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.
STUDENT ROLES & RESPONSIBILITIES

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
EMAIL: ilana.halperin@sunnybrook.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES

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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EMAIL:
Gregory.borschel@sickkids.ca
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PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES

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
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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.
EMAIL: douglas.cheyne@utoronto.ca
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PROJECT DESCRIPTION:
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 deficits.
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 (cheynelab.utoronto.ca).
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
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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.
STUDENT ROLES & RESPONSIBILITIES
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.
EMAIL: noah.ivers@wchospital.ca
PROJECT DESCRIPTION:
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:
1) Develop Content and Assess Patient and Provider Acceptability (Phase 1)
Deliverables: o Develop physical activity screening questionnaire o Integrate screening questionnaire into tablet interface o Develop clinical decisional support algorithm (based on risk stratification) o Collection of codified resources o Develop process & resources to facilitate referrals for patients who would benefit from additional support o Patient usability and satisfaction o Provider satisfaction
2) Research
– Evaluate Effectiveness (Phase 2)
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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.
Deliverables: o Develop protocol o Consent & recruit participants o Knowledge transfer
3) 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.
Deliverables: o 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 o Adaptation
– adapt PROM and process to new health issue o Test
– test approach on a small scale
EMAIL: simone.vigod@wchospital.ca
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PROJECT DESCRIPTION:
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 depression.
STUDENT ROLES & RESPONSIBILITIES
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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.
EMAIL: andrea.kassner@utoronto.ca
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PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
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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.
EMAIL: anne.bassett@utoronto.ca
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PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
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
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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.
EMAIL:
Thomas.forbes@uhn.ca
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PROJECT DESCRIPTION:
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.
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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.
STUDENT ROLES & RESPONSIBILITIES
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.
EMAIL: lianne.singer@uhn.ca
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PROJECT DESCRIPTION:
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
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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.
STUDENT ROLES & RESPONSIBILITIES
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: http://www.tvn-nce.ca/media/51696/tvn-interdisciplinary-training-program-eng-print-sm-2014-01-15.pdf
EMAIL: david.wiljer@camh.ca
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PROJECT DESCRIPTION:
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:
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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 self-monitoring 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.
STUDENT ROLES & RESPONSIBILITIES
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Developing and submitting REB application (CAMH and/or U of T)
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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
EMAIL: nih@smh.ca
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PROJECT DESCRIPTION:
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.
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STUDENT ROLES & RESPONSIBILITIES
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.
EMAIL: lorraine.lipscombe@wchospital.ca
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PROJECT DESCRIPTION:
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
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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.
STUDENT ROLES & RESPONSIBILITIES
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.
EMAIL: mlemaire.lab@sickkids.ca
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PROJECT DESCRIPTION:
STUDENT ROLES & RESPONSIBILITIES
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
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Learn and apply laboratory techniques to study lipid biology
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Familiarity with using cells generated with CRISPR/Cas9 genome editing techniques

Presentation of data at local events and/or at national/international conferences
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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).
EMAIL: david.cescon@uhn.ca
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PROJECT DESCRIPTION:
STUDENT ROLES & RESPONSIBILITIES
EMAIL: andrea.boggild@utoronto.ca
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PROJECT DESCRIPTION:
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 evidence-based 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.
OBJECTIVES
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 "antileishmaniagram".
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.
STUDENT ROLES & RESPONSIBILITIES
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:
1. Assist with development of an assay for the determination of Leishmania "susceptibility" to fluconazole, which may include in vitro culture work, densitometry, and microscopy;
2. Assist with production of an "anti-leishmaniagram" for imported cases of Leishmania to Ontario, which may include real time
PCR and sequencing-based experiments;
3. 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;
4. Assist with in vitro culture, real time PCR, sequencing, and EIA-based experiments related to LRV1 coinfection in leishmaniasis;
5. Synthesis of results into knowledge products such as abstracts for scientific conferences, or peer-reviewed manuscripts;
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6. Apply for competitive funding awards through scientific program committees for presentation of the work at national and international scientific conferences.
EMAIL: leungge@smh.ca
/ crossk@smh.ca
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PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
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.
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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.
EMAIL: natalie.coburn@sunnybrook.ca
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PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
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
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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.
EMAIL: natalie.coburn@sunnybrook.ca

PROJECT DESCRIPTION:
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, realworld 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.
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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.
STUDENT ROLES & RESPONSIBILITIES
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.
EMAIL: kutrykm@smh.ca

PROJECT DESCRIPTION:
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.
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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 .
STUDENT ROLES & RESPONSIBILITIES
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 investigator.
EMAIL: marc.jeschke@sunnybrook.ca
/ saeid.amininik@utoronto.ca

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PROJECT DESCRIPTION:
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 fibroproliferative 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.
STUDENT ROLES & RESPONSIBILITIES
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.
EMAIL: marc.jeschke@sunnybrook.ca
/ saeid.amininik@utoronto.ca

PROJECT DESCRIPTION:
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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 epithelial-like 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 nonimmunogenic umbilical cells and with properties that closely match the pathophysiological features of human skin. Bilayered skin substitute will be developed at throughputs that are ultimately clinically relevant for the treatment of severe burns and characterized in vitro and in vivo .
STUDENT ROLES & RESPONSIBILITIES
Student will evaluate two potential hydrogel and will incorporate our isolated/ well characterised stem cells into the hydrogels. Student will characterise the newly bio-fabricated skin in vitro using different tissue staining methods.
She/He will further characterise the bilayer skin substitute using Scanning Electron Microscopy (SEM), Mercury
Porosimetry and micro Computed tomography ( μCT). These will provide information regarding the scaffold porosity and architecture with and without cells.
With help of our 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.
EMAIL: marc.jeschke@sunnybrook.ca

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PROJECT DESCRIPTION:
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 betaoxidation) 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, 2oxoglutarate 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.
STUDENT ROLES & RESPONSIBILITIES
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.
EMAIL: kcroitoru@mtsinai.on.ca
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
PROJECT DESCRIPTION:
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 celldriven 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 intraperitoneal 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.
STUDENT ROLES & RESPONSIBILITIES
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.
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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.
EMAIL: michael.fehlings@uhn.ca

PROJECT DESCRIPTION:
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.
STUDENT ROLES & RESPONSIBILITIES
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,
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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.
EMAIL: michael.fehlings@uhn.ca

PROJECT DESCRIPTION:
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 addressed.
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 PPAR δ-miR-15a axis and
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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.
STUDENT ROLES & RESPONSIBILITIES
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 curre nt 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.
EMAIL: brown@lunenfeld.ca

PROJECT DESCRIPTION:
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.
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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 antigenpresenting 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
STUDENT ROLES & RESPONSIBILITIES
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 lab.
EMAIL: tu@ices.on.ca

PROJECT DESCRIPTION:
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,
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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 socio-demographic 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 www.canheart.ca
or follow the project on Twitter
@CANHEART_news.
STUDENT ROLES & RESPONSIBILITIES
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 finding s 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.
EMAIL: samira.mubareka@sunnybrook.ca
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PROJECT DESCRIPTION:
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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 reemerging 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 crossdisciplinary 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 par ticle 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 procedure).
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.
STUDENT ROLES & RESPONSIBILITIES
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 develop:
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 completed.
EMAIL:
Daniel.mueller@camh.ca
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PROJECT DESCRIPTION:
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 antipsychoticinduced 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 OMNIgene -GUT 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-07001). 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.
STUDENT ROLES & RESPONSIBILITIES
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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EMAIL: jeff.daskalakis@camh.ca
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PROJECT DESCRIPTION:
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 1/10 th 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 noninferiority 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.
STUDENT ROLES & RESPONSIBILITIES
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Clinical evaluation
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Treatment exposure
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Neurophysiology testing
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Director report will be post-doctoral fellow and/or scientist
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