Our Research Members
Professor, Department of Medicine
Head, Division of Endocrinology & Metabolism, St. Michael’s Hospital
Canada Research Chair in Diabetes Complications
Research in the Gilbert lab focuses on the pathogenesis of diabetes complications as a way to evolve new therapies to prevent their development and attenuate their progression. Current projects involve translational research in diabetic nephropathy, retinopathy and heart failure, exploring novel pharmacological treatments and the use of adult stem cells to regenerate diseased tissue.
Assistant Professor, Faculty of Kinesiology & Physical Education
I am interested in understanding how exercise and nutrition impact carbohydrate and fat metabolism in humans, and identifying lifestyles strategies to improve metabolic health. This ranges from conducting studies in young healthy adults to those at risk for, or afflicted with, metabolic disease. We are interested in practical questions relating to the importance of exercise dose (e.g., intensity vs. duration), mode (e.g., aerobic vs. resistance), and timing (e.g., before vs. after a meal) on indices of metabolic health such as insulin sensitivity and cardiorespiratory fitness. We are also interested in exploring sex-based differences in the adaptive response to exercise and nutritional interventions in an effort to provide sex-specific recommendations for improved health of Canadians.
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
Centre for Research on Inner City Health
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.
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) evaluation of eating behaviours and traits in children and adolescents attending weight management programs in Canada
(v) bariatric surgery outcomes in adolescents
Professor, Department of Nutritional Sciences; Department of Medicine; and Dalla Lana School of Public Health
Associate Scientist, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital
5th Floor, Room 5366/5253
Medical Sciences Building, 1 King's College Circle
Toronto, ON M5S 1A8
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 Indigenous 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
Faculty of Medicine, University of Toronto, C. David Naylor Building
6 Queen’s Park Crescent West, 3rd Floor
Toronto, ON M5S 3H2
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.
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 Nutritional Sciences and Medicine, Faculty of Medicine
Director of Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital
6th Floor, Room 6133Q
61 Queen Street East
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
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
6th Floor, Suite 6122
61 Queen St. East
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 Professor, Teaching Stream
Institute of Biomaterials and Biomedical Engineering (IBBME)
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.
Associate Professor, Department of Biochemistry
Senior Scientist, SickKids
I am an organelle cell biologist who focuses on understanding cellular processes in the perceptive of organelles to understand human diseases. One of my main focus is understanding the role of the metabolic organelles, the peroxisomes. Peroxisomes are metabolic organelles are critical for metabolism of lipids and redox homeostasis. One of our goal is to understand the role of peroxisomes in pathogenesis of obesity and type 2 diabetes mellitus (T2DM). For this reason, my lab has two area of interest in respect to T2DM:
1) There is growing evidence to suggest a potential involvement of peroxisomes in pathogenesis of obesity and type 2 diabetes mellitus (T2DM). For example, plasma levels of nonesterified fatty acids (NEFAs) are increased under the conditions of obesity and adipose dysfunction, which ultimately exert lipotoxicity and promote insulin resistance. Since peroxisomes may play a pivotal role in regulating plasma NEFA levels through governing lipid droplet (LD) formation and fatty acid oxidation in adipocytes, we are studying the role of adipose-peroxisomes can be directly associated with pathogenesis of T2DM.
2) Recently it has been demonstrated that H2O2 generated in peroxisomes rather than in the mitochondria is responsible for NEFA-induced lipotoxicity in pancreatic beta-cells. Therefore, when the elevated levels of NEFAs in obesity exceed the capacity of mitochondrial beta-oxidation, the excess fatty acids will be metabolized via peroxisomal beta-oxidation, leading to increased production of H2O2. Therefore, we are studying whether a lack of peroxisomes in pancreatic beta-cells impedes the inactivation of H2O2, resulting in b-cell dysfunction due to ROS-mediated lipotoxicity.
Department of Molecular Genetics
Although mesenchymal-epithelial interactions play a critical role in organ development and stem cells, little is known about digestive organ-specific stromal signals. Utilizing reporter mice that label pancreatic, stomach and intestinal stromal cells, we analyzed their gene expression and identified pancreatic stroma-specific downregulation of Hh signaling. To investigate how mesenchymal Hh signaling is tightly regulated, we conditionally deleted two Hh negative regulators, Sufu and Spop, in the pancreatic mesenchyme and demonstrated their critical roles in beta cell differentiation during pancreatic development. Since Hh activation increases the expression of gut mesenchymal Wnt ligands, leading to severe defects in beta cell development, in collaboration with Dr. Cristina Nostro’s group, we examined the role of Wnt signaling in hESC differentiation. Notably, Wnt inhibitors such as WIKI4 significantly increased the number of C-PEP+/NKX6.1+ beta-like cells, whereas its agonist, CHIR99021, impaired the expression of pancreatic progenitors and endocrine lineage markers. Our goal is to define the signaling and epigenetic mechanisms of pancreatic niche signals for beta cell maturation and function.