Our Research Members
Professor, Department of Medicine
Staff Physician (Nephrology), University Health Network and Mount SinaiHospital
200 Elizabeth Street, Room 8N-859
Toronto, ON M5G 2C4
Research in my laboratory at the University of Toronto is focused on cellular and molecular mechanisms responsible for the development of diabetic nephropathy. In particular we study the role of the renin angiotensin system (RAS) in diabetic nephropathy and the link between the RAS, obesity, and activation of NADPH oxidase. We utilize transgenic mice in our approach and have combined whole animal studies with cell culture experiments to define cellular mechanisms of injury. We are currently studying mice with deletions in the genes for ACE2, p47, and adiponectin. Our laboratory also collaborates with investigators in the Human Physiology Laboratory at the University Health Network, Mount SinaiHospital, and the Hospital for Sick Children on studies of kidney function and urine proteomics in humans with diabetic nephropathy.
Associate Professor, Department of Biochemistry
Senior Scientist, Sunnybrook Research Institute
2075 Bayview Avenue, Room M7 617
Toronto, ON M4N 3M5
Phone: 416-480-6100 x5743
My lab is interested in understanding how human cells respond to extracellular cues to maintain and ensure their function and survival. One central focus is to study how the pancreatic beta cell converts feeding cues into signals leading to insulin production and secretion. We use high-throughput functional screens to identify novel players involved in different cell-signaling pathways, including human pancreatic beta cell proliferation and those involved in the maintenance of mitochondria, critical subcellular organelles essential for cell function and survival. In addition to Type 1 and Type 2 diabetes, our work impacts upon cancer and neurodegeneration.
Professor, Institute of Biomaterials and Biomedical Engineering
Biomaterials and tissue engineering. Delivery of islets and pseudo-islets into vascularized, subcutaneous tissue, including microencapsulation and immune modulation using dendritic cells.
Associate Professor, Department of Medicine
Associate Professor, Institute for Health Policy, Management and Evaluation
Staff Endocrinologist, Sunnybrook Health Sciences Centre
Senior Scientist, Institute for Clinical Evaluative Sciences
Scientist, Sunnybrook Research Institute
2075 Bayview Avenue, Suite G106
Toronto, ON M4N 3M5
My research focus is on the quality of and outcomes of diabetes care. Much of this work is done using linkage of large health care administrative data bases. My three main areas of interest are: a) the influence of different care models on diabetes quality and outcomes, b) gestational diabetes care and outcomes, and c) diabetes in vulnerable populations, including ethnic, immigrant and aboriginal communities.
Assistant Professor, Department of Pediatrics
Assistant Professor (Status-Only), Institute of Health Policy, Management, and Evaluation
Staff Physician, The Hospital for Sick Children
Scientist-track Investigator, The Hospital for Sick Children Research Institute
Adjunct Scientist, Institute for Clinical Evaluative Studies
555 University Ave.
Toronto, ON M5G 1X8
My research program is focused on developing and evaluating health services interventions to improve health outcomes and the quality of care for youth living with diabetes as they transition to adult care. I am particularly interested in developing and evaluating interventions that leverage existing population-level administrative datasets to inform health system change. I work with teams of researchers from disciplines including health service research, implementation science, and quality improvement.
Associate Professor, Department of Nutritional Sciences, Faculty of Medicine
Consultant Physician, Division of Endocrinology and Metabolism, St. Michael’s Hospital
Scientist, Li Ka Shing Knowledge Institute, St. Michael’s Hospital
Knowledge Synthesis Lead, Toronto 3D Knowledge Synthesis and Clinical Trials Unit, St. Michael’s Hospital
My research program continues to strive to identify and investigate important diet and disease questions in the area of cardiometabolic risk and diabetes. We use knowledge synthesis techniques (systematic reviews and meta-analyses) and randomized controlled trials to address the need for high quality data to inform clinical practice guidelines and public health policy, as well as guide the design of future trials. Clinical practice guidelines and public health policy are moving away from the more traditional macronutrient-centric dietary approaches (“low-fat”, “low-carb”, “high protein”) to more food and dietary pattern based approaches. I have helped to initiate and steer this change in the 2013 guidelines of the Canadian Diabetes Association (CDA) and the upcoming 2015 guidelines of the European Association for the study of diabetes (EASD). My research program has attempted to keep up with this modernization, as reflected in the main ongoing food and dietary pattern based foci of my research program: sugars (fructose, sucrose, high fructose corn syrup), dietary pulses (beans, peas, chickpeas, lentils), tree nuts, and portfolio and low glycemic index dietary patterns.
Assistant Professor, Department of Surgery
Scientist, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto
Background: Germ-line mutations in the tumor suppressor gene BRCA2 (breast cancer 2, early onset) predispose carriers mostly to breast cancer, and BRCA2 mutation carriers also face a 2-fold increase in the risk of developing diabetes. Hyperglycemia, the hallmark of diabetes, is a major risk factor for endothelial dysfunction leading to vascular complications. The relationship linking role of BRCA2 in the development of diabetes and endothelial dysfunction remains mainly unexplored.
Methods: To elucidate the role of BRCA2 in diabetes and endothelial apoptosis/dysfunction in vitro, we silenced BRCA2 in human umbilical vein endothelial cells (ECs) and evaluated the markers of EC function and apoptosis following hyperglycemia.
Results: We first confirmed the basal expression of BRCA2 in ECs at transcript and protein levels by qPCR and immunoblotting, respectively. Interestingly, hyperglycemia significantly induced BRCA2 expression after 48 hours of treatment. We then silenced BRCA2 in ECs and confirmed successful silencing at transcript and protein levels. Hyperglycemia significantly increased the reactive oxygen species (ROS) production in the BRCA2-deficient ECs in comparison to control ECs. Increased ROS production was associated with exacerbated DNA-damage in BRCA2-silenced ECs as evidenced by increased expression and activation of DNA double-stranded breaks (DSBs) marker H2A.X and reduced RAD51-foci formation, an essential regulator of DSB repair. Increased DSBs were associated with significantly increased activation of p53. Elevated levels of DNA-damage and activated-p53 were further associated with significantly increased hyperglycemia-induced apoptosis in BRCA2-silenced ECs as measured by immunoblotting for cleaved-caspase-3, Bax and by TUNEL-staining. Key indices of endothelial function, including tube formation and NO production, were significantly reduced following hyperglycemia-treatment in BRCA2-deficient ECs.
Conclusion: Our data for the first time, show an entirely novel role of BRCA2 as a regulator of endothelium in the setting of hyperglycemia, and provide important clues regarding the potential susceptibility of BRCA2 mutation carriers to hyperglycemia-induced cardiovascular complications.
Assistant Professor of Medicine
585 University Ave.
Toronto, Ontario M5G 2N2
I am a Transplant Nephrologist in the Division of Nephrology at the Toronto General Hospital with additional training in diabetes care in transplant recipients and pancreas transplantation as a treatment option for patients with Type 1 diabetes. In collaboration with Dr. David Cherney, I am currently a site investigator/Co-Investigator at UHN for two clinical trials: 1) DAPA CKD: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease and 2) A double-blind, placebo controlled, cross-over renal mechanistic trial to assess the effect of adding empagliflozin versus placebo on renal hyperfiltration in patients with type 1 diabetes on a background of the angiotensin converting enzyme inhibitor (ACEi) Ramipril: BETWEEN study. I also have a research interest in Pancreas Transplantation. I am currently a Co-Investigator (PI: Dr. Cherney, Co-I: Dr. Kim, Dr. Cattral) on a pilot study evaluating the impact of pancreas transplantation on the complications of Type 1diabetes (BBDC Sun Life Financial Pilot and Feasibility Grant) and have published clinical outcomes research in patients with type 1 diabetes with pancreatic transplants. I also have interest in understanding the pathogenesis of recurrent diabetic kidney disease (DKD) in the kidney allograft and therapies for DKD in the transplant population. Our group has recently published our experience describing the safety and efficacy of SGLT2 inhibitors in a group of kidney and kidney-pancreas transplant recipients.
Associate Professor, Department of Paediatrics, University of Toronto
Co-Director, Bone Health Centre, The Hospital for Sick Children.
Paediatric Endocrinologist, Department of Paediatrics, Division of Endocrinology, The Hospital for Sick Children.
Project Investigator, Research Institute, The Hospital for Sick Children.
555 University Avenue, Room 5114
Toronto, ON M5G 1X8
Cardio Renal Dysfunction in Type 1 Diabetes:
Over the last 15 years, the direction of my renal research activities has been in understanding the early pathophysiology of diabetic nephropathy in adolescents with type 1 diabetes. This area is widely acknowledged as being central to the prevention of diabetic nephropathy. My efforts have involved the development and use of methodologies for measurement of urinary growth factors, ambulatory blood pressure monitoring and renal hemodynamic testing. Study directions in this patient population have included; (a) the natural history of expression and progression of microalbuminuria (CV ref; 13, 21, 22) (Grant; PSI; 122,000) (Fellow: Lawson, M); (b) determinants of microalbuminuria expression i. Puberty; ii. Urinary Growth Factors (growth hormone, IGF-1 and TGG-beta); iii. Kidney size; iv. Dietary protein intake (14, 19, 24, 27) (PSI; 137,000) (Cummings, B). (c) the natural history of hypertension expression using Ambulatory Blood Pressure Monitoring (17) (d) The interaction between hypertension and microalbuminuria expression (Jefferies, C). (e) The relationship between diurnal blood pressure changes and glomerular hemodynamic alterations (34, CIHR 108, 773 – and Div Funds 34,000; Curtis, J). My role in this program includes, the underlying conceptual basis, supervision of the day to day administration and responsibility for the academic outcomes.
Over the last 8 years, I have developed a collaborative relationship with 3 adult nephrologists at the Toronto General Hospital, Dr. Judith Miller, Dr. James Scholey and Dr. David Cherney. The focus of these more recent studies is the control and modulation of glomerular hemodynamic function in adolescents and young adults with uncomplicated type 1 diabetes. Two studies have been completed and published (Renin Angiotensin Inhibition (CIHR) and Renal Hemodynamic function and COX2 Inhibition (JDRF) and Renal Hemodynamic Function). A third Nitric Oxide (CIHR) and Renal Hemodynamic function has just been completed and the results are being written up. Funding is being applied for 2 further studies; specifically; Vitamin D and Rental Hemodynamic Function and Growth Hormone Inhibition and Renal Hemodynamic Function. Our current team comprises of Dr. David Cherney (Clinician Scientist, Division of Nephrology, Dept. of Medicine), Dr. James Scholey (Clinician Scientist, Division of Nephrology, Dept. of Medicine), Dr. T. Bradley, a Paediatric Cardiologist, Ria Dekker (Research Assistant) and Yesmino Elia (Research Manager). The principle achievements include (i) papers in Diabetes, Kidney International and Journal of the American Society of Nephrology and more recently in Diabetes Care (ii) providing evidence that the hyperfiltration state in diabetes is mediated by factors other than the rennin angiotensin system (iii) completion of the COX2 and NO grants and (iv) the addition of Dr. J. Scholey to the group of investigators.
I am also participating as a member of the HSC team in a multinational ‘Adolescent Type 1 diabetes Cardio-Renal Protection Study (AdDIT)’. Dr. D. Dunger (Cambridge, England) is the overall Principal Investigator and Dr. D. Daneman, the HSC PI. I was responsible for the Screening Phase (Protocol: Screening for Microalbuminuria in Type 1 diabetes) in which 500 adolescents with Type 1 diabetes were screened on two separate occasions with three early morning urines in 2008. I am currently responsible for the Observational Phase which commenced September 2011 and runs until 2016. I also initiated, with our Co-Authors at Toronto General Hospital, an Ancillary Study to the Observational Arm of AdDIT in which markers of renal inflammation will be measured in the urine in a sub-cohort of the Observational Arm over a duration of the study. This will allow us to address several questions regarding urinary proteomics and the development of renal and cardiovascular disease in adolescents with Type 1 diabetes.
Professor, Department of Ecology and Evolutionary Biology, Faculty of Arts and Science
Co-director of the Child and Brain Development Programme, Canadian Institute for Advanced Research
The Drosophila melanogaster corpora cardiaca (CC) is functionally homologous to the mammalian pancreatic alpha cells and anterior pituitary gland. The CC is the site of biosynthesis and secretion of the fly glucagon homolog, adipokinetic hormone (AKH). The foraging gene (for) in D. melanogaster encodes a cGMP-dependent protein kinase (PKG) and is evolutionarily conserved across taxa. for has a well-established role in the regulation of feeding behavior and metabolism. We have identified a CC-specific role for for in the regulation of adult feeding behavior, lipid metabolism, and starvation stress response. Our research uncovers a novel role for foraging and PKG in the CC, and begin to elucidate a putative mechanism whereby juvenile experience can influence adult metabolism and health outcomes.
Professor Emeritus, Departments of Medicine and of Physiology
200 Elizabeth Street, Room 12EN213
Toronto, ON M5G 2C4
Diabetes, lipoproteins and atherosclerosis.
Associate Professor, PhD Supervisor
Department of Surgery, Division of Anatomy; Institute of Medical Science; Department of Physiology; Department of Pharmacology and Toxicology; Heart and Stroke Richard Lewar Centre of Excellence; Collaborative Program in Neuroscience (CPIN); Cardiovascular Sciences Collaborative Program (CSCP); Faculty of Medicine, University of Toronto
1 King's College Circle
Toronto, ON M5S 1A8
Research interest is in studying the role of ion channels (K(ATP) and TRPM2, etc.) in diabetes and stroke in diabetes, neuroprotection, and drug development, using in-vivo animal models of human diseases in combination with genomic analyses, advanced imaging, electrophysiology, and functional and behavioral assessments.
Publication related to diabetes research: Cerebrovascular safety of sulfonylureas: the role of K(ATP) channels in neuroprotection and the risk of stroke in patients with type 2 diabetes. Diabetes. 2016, 65(9): 2795-2809
Assistant Professor, Department of Laboratory Medicine and Pathobiology
Scientist, Physiology & Experimental Medicine, Hospital For Sick Children
My lab is studying Obesity, Metabolism and Diabetes at The Hospital for Sick Children. Our research focus includes:
1) patho-physiology of adipose tissue expansion and its causal role in metabolic defect and diabetes
2) identification of adipocyte precursor cells and its metabolic function by using mouse model
Assistant Professor, Department of Pharmacology & Toxicology, and School of Graduate Studies
Scientist, Sunnybrook Research Institute
My research examines neuroendorcrine contributions to mood and cognitive symptoms in type 2 diabetes. My lab conducts clinial studies, primarily of people with type 2 diabetes undertaking exercise-based rehabilitation and education interventions. We have a particular interest in the roles of cerebrovascular disease (including stroke and microagniopathy) in the effects of type 2 diabetes on the brain. We use neuroimaging, metabolomic and neurocognitive techniques.