Our Research Members
Associate Professor, Department of Laboratory Medicine & Pathobiology
Academic Director, Microscopy Imaging Laboratories (MIL), Faculty of Medicine
We study the role of a mitochondrial named NLRX1 in diabetes. Our preliminary research has identified that NLRX1 plays a role in the regulation of body weight and of obseity-induced diabetes in vivo. Because NLRX1 was identified as a key regulator of apoptosis during inflammation, we are interested in identifying how this mitochondrial protein links obesity and diabetes with inflammation and cell death.
Professor, Department of Family and Community Medicine
Senior Scientist, Institute for Clinical Evaluative Sciences
Scientist, Centre for Research on Inner City Health, St. Michael’s Hospital
30 Bond Street
Toronto, ON M5B 1W8
Phone: 416-864-6060 x77444
Diabetes in primary care – processes of care, impact of incentives, health disparities.
Risk factors for diabetes, especially socioeconomic status, ethnoracial background and immigration, neighbourhood walkability.
Associate Professor, Faculty of Dentistry; Faculty of Medicine
Hospital For Sick Children, Mount Sinai Hospital, Sunnybrook Health Sciences Centre, and Toronto Rehab
Impact of diabetes on innate immunity and neutrophil functions. Impact of diabetes on oral health and periodontal diseases. Impact of diabetes on osteoimmunology.
Professor, Department of Nutritional Sciences
Senior Scientist, Rotman Research Institute, Baycrest
Research in the Greenwood lab is focused on understanding the effect of diet and metabolic disorders, including type 2 diabetes, on the retention or loss of cognitive function with aging. Our studies, in both humans and animal models, show that the consumption of diets which promote obesity and type 2 diabetes are associated with more rapid decline in cognitive function. By contrast, consumption of healthy diets associates with retention of cognitive function. Our current interest lies in understanding the adverse brain effects of type 2 diabetes. These studies draw on functional magnetic resonance imaging as a means of determining underlying neuronal pathways and neuronal responses which are impacted.
Professor, Department of Laboratory Medicine and Pathobiology
Director, Bone and Mineral Group
Our research focuses on the effects of diabetes on the skeletal system using pre-clinical models. Examples of our research includes:
1) Effect of Vanadium Treatment on Bone Loss and Bone Quality in Rat Models of Diabetes. Vanadium compounds have been shown to be effective in experimental diabetes and insulin-resistant hypertension. However, these agents are known to accumulate in bone mineral where vanadate substitutes for phosphate. It is therefore essential to understand the long-term effects on these compounds on bone quality. (Facchini DM, Yuen VG, Battell ML, McNeill JH, Grynpas MD. The effects of vanadium treatment on bone in diabetic and non-diabetic rats. Bone. 2006; 38(3):368-77)
2) The effect of Rosiglitazone treatment on bone quality in rat models of type 2 diabetes and osteoporosis. Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat patients with Type 2 Diabetes Mellitus (T2DM) to improve glycemic control. The ADOPT clinical trial showed that women taking RSG experienced more fractures. The purpose of our study is to understand the mechanism by which RSG induces limb fracture and alters bone quality in the insulin resistant Zucker Fatty rat.
3) Comparison of the skeletal effects in the treatment of type2 diabetes with Sitagliptin (a DPP4 inhibitor) or Pioglitazone (a PPRgamma agonist) in mice fed a high fat diet.
Assistant Professor, Department of Psychiatry
Clinician Scientist, Centre for Addiction and Mental Health, Complex Mental Illness
Director of Research, Mental Health and Metabolism Clinic, Centre for Addiction and Mental Health
250 College St.
Toronto, ON M5T 1R8
Phone: 416-535-8501 x4368
Dr. Hahn is a psychiatrist by training, who joined the University of Toronto (U of T) Faculty this spring following completion of a PhD, through the Institute of Medical Sciences, U of T. Her research interests lie in disentangling the complex relationship that underlies the illness of schizophrenia and the 3-5 fold increased risk of type 2 diabetes observed in this population. Her group’s preclinical work has focused on understanding the contribution of antipsychotic medications (which remain the cornerstone of treatment for the illness, but are linked with significant metabolic side-effects) to the risk of glucose dysregulation. Her work to date to elucidate underlying diabetogenic mechanisms of antipsychotics has pointed to specific neurotransmitter systems (i.e. dopaminergic, serotonergic, muscarinic), as well as centrally-mediated mechanisms. As a translational researcher, Dr. Hahn’s work has spanned preclinical rodent and human models of antipsychotic-induced glucose perturbations, including use of complex techniques to measure glucose metabolism (i.e. euglycemic and hyperglycemic clamps, the Frequently Sampled Intravenous Glucose Tolerance Test), and has advanced to studying clinical interventions to mitigate these side-effects.
Associate Professor, Department of Paediatrics, Division of Endocrinology, Director, Centre for Healthy Active Kids
Senior Associate Scientist, Physiology and Experimental Medicine, SickKids Research Institute
My research interests include the clinical and physiologic manifestations of insulin resistance and pancreatic beta cell function in the pediatric age group. I am also interested in treatment studies of childhood obesity. Recent studies include:
(i) risk for diabetes and metabolic syndrome and pathophysiologic mechanisms related to the development of hypothalamic obesity in children treated for craniopharyngioma;
(ii) early life risk factors for the development of obesity and diabetes in infants born to women with gestational diabetes;
(iii) incidence and clinical presentation of type 2 diabetes in Canadian children (iv) role of ectopic fat deposition and metabolic consequences in obese children and adolescents
(v) bariatric surgery outcomes in adolescents
Associate Professor, Department of Nutritional Sciences; Department of Medicine; and Dalla Lana School of Public Health
Canada Research Chair in Diabetes Epidemiology
Associate Scientist, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital
150 College Street
Toronto, ON M5S 3E2
Dr. Hanley’s research interests include the metabolic and nutritional epidemiology of type 2 diabetes and related disorders including obesity, insulin resistance, and beta cell dysfunction, as well as the micro-and macro-vascular complications of type 2 diabetes. His research focuses on diabetes in Aboriginal Canadian communities and other high-risk populations. Current projects include the Sandy Lake Health and Diabetes Project, the PROMISE study, as well as collaborations with the Insulin Resistance Atherosclerosis Study and the Gestational Diabetes and Acute Phase Biomarkers research groups.
Sir John and Lady Eaton Professor and Chair of Medicine
Professor and Clinician Scientist, Division of Rheumatology, Department of Medicine, WCH/Women’s College Research Institute
Professor, Institute for Health Policy, Management and Evaluation, Dalla Lana School of Public Health
Senior Adjunct Scientist, ICES
Toronto, ON M5G 2C4
I am a clinical epidemiologist/health services researcher in the field of osteoarthritis (OA) – I have conducted observational studies examining the relationship between OA and diabetes. Among other findings, we have shown that difficulty walking due to hip or knee OA is an independent risk factor for diabetes complications in people with OA and diabetes, and also a risk factor for incident diabetes.
Associate Professor, Department of Physiology, Faculty of Medicine
Many physiologic processes are mediated by a group of switch-like heterotrimeric G proteins. G proteins are normally coupled to receptors on the cell surface to act as intracellular relays between environmental stimuli and the rest of the cell. Our work defines the biologic importance for precise kinetic regulation of G-protein-mediated signaling events.
Regulation of G-protein signaling pathways: The G-protein heterotrimer is composed of a GDP-bound G alpha subunit and a G beta gamma heterodimer. Upon G-protein activiation, the Galpha subunits are free to engage appropriate downstream effector pathways. Effector signaling is terminated following G alpha catalysed hydrolysis of GTP and reformation of the quiescent receptor-coupled heterotrimer. RGS proteins are a family of GTPase activating proteins (GAPs) for G alpha subunits. By increasing the intrinsic rate of GTP hydrolysis for G alpha subunits, RGS proteins impact GPCR-mediated signaling pathways by: i) promoting faster signal termination kinetics following removal of a physiologic GPCR agonist; and ii) decreasing GPCR agonist sensitivity (i.e. higher agonist concentrations are needed to achieve the same degree of signaling). Our work is aimed at defining the molecular mechanisms that regulate the function of RGS proteins in vivo . Using a combination of physiology, biochemistry, cell biology, pharmacology, and genetics we examine how subcellular localization, G-protein selectivity and interaction with other cellular signaling components regulates the function of RGS proteins in living organisms.
Regulation of G-protein signalling in Pancreatic Islet beta cells: Previous work has shown that one RGS protein family member, RGS4, is highly expressed in beta cells and its function can have profound physiologic effects on insulin secretion. Although the majority of the work in this field has been focussed on the role of RGS4 at the plasma membrane, our recent studies have identified a novel intracellular location for RGS4, the preautophagosome, where it can regulate the autophagic flux and metabolic homeostasis within beta cells. Notably, activated Galphai3 is a potent attenuator of autophagic activity. Accordingly, our work is aimed at understanding the role of RGS4 in the regulation of autophagic flux and enery homeostasis in pancreatic islet beta cells.
Associate Professor, Faculty of Medicine
Head, Divisions of Nephrology and Obstetric Medicine, Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room A206
Toronto, ON M4N 3M5
Phone: 416-480-6100 x3863
Dr. Hladunewich completed her Nephrology Fellowship at Stanford University Medical Center. In addition to her research training in glomerular physiology, she completed a Master’s of Science in Clinical Investigation at Stanford University. Her primary research interest is the long-term sequelae of preeclampsia, including abnormalities in the renin angiotensin system, endothelial dysfunction, insulin resistance and an increased risk for the metabolic syndrome. She also conducts physiologic and outcomes research in young women with pregnancies complicated by diabetic nephropathy. She is a co-investigator in a CIHR-funded study examining the risk of microalbuminuria in women with gestational diabetes.
Professor, Department of Laboratory Medicine and Pathobiology
Research in the Irwin lab focuses on the evolution of genes involved in diabetes. Many of the genes and proteins (e.g., the proglucagon-derived peptides glucagon, GLP-1, and GLP-2) involved in glucose metabolism are related yet have differing function. By examining the origin and evolution of these genes we hope to identify portions of the sequences important for their unique functions. We are also interested in role of liver-specific glucokinase in glucose metabolism. We are currently using comparative and molecular approaches to identify regulatory sequences essential for regulation of expression, including insulin induction, of the glucokinase gene in the liver.
Professor, Departments of Medicine and Nutritional Sciences, Faculty of Medicine
Director of Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital
61 Queen Street East, 6th Floor, Room 6133Q
Toronto, ON M5C 2T2
Dr. Jenkins research area is the use of diet in the prevention and treatment of hyperlipidemia and diabetes. He has over 200 original publications on these and related topics. His team was the first to define and explore the concept of the glycemic index of foods and demonstrate the breadth of metabolic effects of viscous soluble fiber, including blood glucose and cholesterol lowering. His studies on combining cholesterol lowering food components (dietary portfolio) have been recognized as creating an effective dietary alternative to drug therapy (statins) for many people and was the only dietary approach referenced in the update of the guidelines of the US National Cholesterol Education Program (ATP III).
Professor, Department of Medicine, Division of Endocrinology & Metabolism
101 College Street, Room 10-354
Toronto, ON M5G 1L7
A) Mechanisms Underlying the Production and Function of the Incretin Hormone GLP-1. The proglucagon gene (Gcg) encodes three major peptide hormones, namely glucagon (produced in pancreas), glucagon-like peptide-1 (GLP-1) and GLP-2 (both are produced mainly in intestines). These hormones exert opposite or overlapping functions in controlling blood homeostasis, food intake, cell growth and proliferation. Based on the features of GLP-1, two new categories of drugs, namely GLP-1 analogues and DPP-IV inhibitors, have been developed for T2D treatment. We are exploring mechanisms underlying the production and function of peptide hormones encoded by Gcg, including GLP-1. We are now studying the role of Wnt signalling and the crosstalk between Wnt and other signalling pathways in regulating the expression and function of GLP-1.
B) Mechanisms Underlying the Expression and Function of the Lipogenic Gene Carbohydrates Response Element Binding Protein (ChREBP). The transcription factor ChREBP is a “master controller” of lipogenic genes that encode a battery of enzymes for converting carbohydrates into lipids. The function of ChREBP can be turned on by hyperglycemia and its expression was shown to be increased in obesity and hyperinsulinemia animal models. We are studying molecular mechanisms underlying the expression of ChREBP and its targets.
Professor of Medicine and Nutritional Sciences
Division of Endocrinology and Metabolism, St. Michael’s Hospital
61 Queen St. East, 6th Floor, Suite 6122
Toronto, ON M5C 2T2
Often with an emphasis in clinical nutrition, I have obtained peer review and non peer review grants (mostly Phase II and III pharmaceutically funded multicentre national and international studies) as Principal, Co-principal or Co-investigator. These studies have investigated the effects of various new drugs on diabetes control, hyperlipidemia and prevention and treatment of diabetes complications. I have been particularly interested in the nutritional management of diabetes with other colleagues in the Department of Nutritional Sciences (Jenkins, Wolever). We have promulgated the concept of the glycemic index of foods and the importance of meal frequency as therapeutic principles.
Associate Director – Undergraduate (IBBME)
Institute of Biomaterials and Biomedical Engineering (IBBME); and Department of Medicine
My research interest is focused on Fibroblast Growth Factor receptor (FGFR) expression and signaling in adult beta cells. We have identified control of FGFR1-expression and -signaling by modifications in the beta-cell extracellular microenvironment. We are now investigating the role of the novel kinase-deficient FGFR5 isoform in the regulation of beta-cell FGFR1-signalling. Using insulin-secreting cell lines, we have expression of FGFR5 at both the cell membrane as well as in association with insulin secretory granules. Expression of FGFR5 enhances classical intracellular FGF-mediated signaling pathways, cellular matrix adhesion as well as insulin content. Expression of a ‘dominant-negative’ (kinase-deficient) isoform of classical FGFR1 (similar in structure to FGFR5) has been shown to induce a diabetic phenotype in mice. Taken together, these data promote our interest in defining the role that FGFRs play in normal beta-cell maintenance and insulin secretion. We currently examine this receptor signaling system using methods of fluorescence microscopy (live-cell and fixed) both in vitro as well as in vivo (whole islet), and verify our results in combination with traditional biochemical techniques.
Professor, Department of Paediatrics; Department of Biochemistry; and Department of Physiology
Senior Scientist, The Hospital For Sick Children
We study how insulin stimulates glucose entry into muscle and how this fails in insulin resistance and type 2 diabetes. We explore insulin signals, movement of vesicles containing glucose transporter 4 (GLUT4) and strategies to render muscle cells insulin-resistant. We generated platforms of muscle cells in culture expressing tagged GLUT4 and a number of insulin signals, as well as transgenic mice expressing tagged GLUT4 in muscle, to test GLUT4 movement in vivo. With these systems we found that signals downstream of PI3-kinase bifurcate into activation of Akt and of the small G protein Rac. Downstream of Akt lies AS160 that regulates the small G proteins Rab8A and Rab13 to control GLUT4 vesicle arrival near the membrane. GLUT4 vesicles arriving at the plasma membrane (in the TIRF-imaging zone) then tether to actin filaments through the molecular motor Myosin 1c. In turn, Rac controls actin filament remodelling, crucial for GLUT4 vesicle translocation to the membrane, and our collaborator Erik Richter (Copenhagen) found that mice lacking Rac in muscle become insulin-resistant. Moreover, overexpressing Rac in cells overcame insulin resistance.
Recently we discovered that the saturated fatty acid palmitate renders macrophages inflammatory, to produce cytokines that make muscle cells insulin-resistant. Moreover, direct activation of the NOD innate immunity recognition receptors, in cells or in vivo, caused insulin resistance. Finally, we documented a particular infiltration of inflammatory macrophages in the muscles of high fat-fed mice and of obese, insulin-resistant humans. These collective findings contribute to our understanding of the link between inflammation and insulin resistance.
Assistant Professor, Department of Ophthalmology and Vision Sciences
Eye Physician and Surgeon and Medical Retina Specialist, Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room M1202b
Toronto, ON M4N 3M5
My current research interest is in retinal vascular diseases including diabetic macular edema. We have demonstrated the importance of serum biomarkers in the role of diabetic retinopathy. Currently, we are measuring cytokines drawn from the aqueous humor in patients with diabetic macular edema to determine if they can predict responses to treatment with intravitreal lucentis injections. The goal of this research is to ultimately use aqueous humor cytokines to guide treatment decisions with various intravitreal medications including anti-VEGF agents, and steroids, in the management of diabetic macular edema.
Assistant Professor, University of Toronto
Associate Member, Institute of Medical Science
Transplant Nephrologist, Department of Medicine, Division of Nephrology, University Health Network
Scientist, Toronto General Hospital Research Institute
Associate Staff, Division of Nephrology, Mount Sinai Hospital
585 University Avenue, 11-PMB-189
Toronto, ON M5G 2N2
My research program has three projects directly related to diabetes:
1) Angiotensin II is a peptide produced in the kidney that leads to progression of diabetic kidney disease. We have identified a group of proteins regulated by angiotensin II in kidney cells and demonstrated that these proteins were involved in kidney fibrosis. We have also demonstrated that measurements of these proteins in urine correlate with kidney fibrosis. We are now studying the mechanisms of regulation of these angiotensin II-activity proteins. Agents that inhibit these proteins may represent new potential treatments of diabetic and other kidney diseases.
2) The mechanisms leading to development of early diabetic nephropathy are still poorly understood. By studying the urinary peptidome of patients with juvenile diabetes mellitus type I and no known diabetic complications, we have identified several peptides of protein uromodulin. We are now investigating the potential function of these peptides and proteases that cleave them from uromodulin, in order to enhance our understanding of the early events leading to kidney injury in type I diabetes.
3) Male sex has been associated with increased risk of progression of kidney disease. We have recently discovered that male sex hormones affect metabolic enzymes in kidney cells and may result in maladaptive metabolic changes in the kidney. These effects were demonstrated in two different animal models of diabetes, where male animals had increased expression of these enzymes and increased kidney hypertrophy and oxidative stress. We are now investigating how sex hormones affect metabolism in kidney cells and whether we can modify the maladaptive effects of testosterone through manipulation of metabolism.
Assistant Professor, Department of Medicine, Division of Endocrinology and Metabolism
Clinician-Scientist, Mount Sinai Hospital
60 Murray Street, Suite L5-029
Toronto, ON M5T 3L9
My clinical research focuses on (i) the impact of obesity on metabolic dysfunction, (ii) the pathophysiology and risk factors for the development of type 2 diabetes mellitus (T2DM), (iii) risk factors for cardiovascular disease in individuals with metabolic abnormalities, and (iv) strategies for the treatment of T2DM. I am particularly interested in understanding the pathophysiology of T2DM in individuals with various degrees of obesity and differential patterns of body fat distribution.