Our Research Members
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), Temerty 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.
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.
Associate Professor, Department of Psychiatry
Associate Member, Institute of Medical Sciences
Clinician Scientist, Centre for Addiction and Mental Health (CAMH),
Complex Mental Illness
Director, Mental Health and Metabolism Clinic, Centre for Addiction and Mental Health
250 College St.
Toronto, ON M5T 1R8
Phone: 416-535-8501 x34368
Dr. Hahn is a clinician-scientist at the CAMH whose research interests lie in translational work focused on the complex interplay between mental illness, antipsychotic treatments, and cardiometabolic risk, with a special interest in type 2 diabetes. Given the early accrual of metabolic risk leading to a 20% reduction in life expectancy for patients with schizophrenia and other severe mental illnesses, she has an interest in treatment and prevention strategies of so called “modifiable” cardiovascular risk factors. She is leading a number of clinical trials focus on targeted pharmacological interventions to reduce metabolic burden and improve other domains of health (i.e. psychopathology, cognition, quality of life) in this population. She is the director of the Mental Health and Metabolic Clinic at the CAMH, which specializes in metabolic monitoring, and interventions for metabolic risk factors in individuals with serious mental illness. She also oversees a basic science laboratory which conducts cutting edge research examining mechanisms (focusing on the central nervous system) of high rates of obesity and diabetes in those receiving psychotropic treatments. Dr. Hahn holds the Cardy Schizophrenia Research Chair at CAMH.
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
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
Temerty 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, Temerty 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.
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 of Medicine
Medical Director, Toronto Liver Transplant Program, Ajmera Transplant Centre
University Health Network
MaRS Building, 9th floor, room 9107
585 University Ave.
Toronto, ON M5G 2N2
Elmar Jaeckel is a trained gastroenterologist/hepatologist as well as endocrinologist/diabetologist and transplantation specialist. He is Medical Director of the Liver Transplant Program at the Ajmera Transplant Centre, University Health Network. Since 2003, he has been leading the research group on immune tolerance and metabolic inflammation at the Hanover Medical School. The group is focusing to establish tissue-specific tolerance in autoimmunity, transplantation and metabolic inflammation.
His working group, Immune Tolerance, aims in establishing immune tolerance in type 1 diabetes and after biological beta cell replacement. For this purpose, he is developing new cell and gene therapy approaches. He is involved in pursuing islet xenotransplantation in Germany and to facilitate tolerance to stem cell derived beta cells. One major research focus is the change of specificity of regulatory T cells for beta cells by the use of chimeric antigen-receptors (CARs). In addition, he aims in local control of immune responses in metabolic inflammation in NASH patients.
He has published numerous articles on viral hepatitis, autoimmune liver disease, autoimmune diabetes and islet transplantation tolerance. He developed tissue-specific regulatory T cell therapies for local tolerance induction, which are currently being tested in clinical trials. He has numerous patents on tolerance inducing therapies and is co-founder of Quell Therapeutics aiming to develop clinical therapies for tolerance induction with regulatory T cells.
Professor, Departments of Nutritional Sciences and Medicine, Faculty of Medicine
Director of Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital
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.
Assistant Professor, Department of Medicine, University of Toronto
Clinician Scientist, Toronto General Hospital Research Institute
Staff Endocrinologist, Toronto General Hospital, University Health Network
200 Elizabeth St.
Toronto, ON M5G 2C4
Dr. Calvin Ke received his Doctor of Medicine from the University of Toronto. He completed his residency training in Internal Medicine at the University of British Columbia and Endocrinology and Metabolism at the University of Toronto. He completed his PhD in clinical epidemiology and global health as a Global Scholar at the Institute of Health Policy, Management and Evaluation, University of Toronto. He served as an Honorary Visiting Scholar at The Chinese University of Hong Kong. He provides clinical outreach services for Chinese-speaking communities with the CareFirst Family Health Team.
Dr. Ke’s research focuses on young-onset type 2 diabetes (individuals diagnosed with type 2 diabetes before the age of 40 years), and on type 2 diabetes in Chinese and South Asian populations. He applies clinical epidemiological methods to characterize the burden, management, and outcomes of type 2 diabetes in both local and global populations across China and India. He is a member of the International Diabetes Federation Atlas Committee and the NCD Risk Factor Collaboration.
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.
Professor, Department of Paediatrics; Department of Biochemistry; and Department of Physiology
Senior Scientist, The Hospital For Sick Children
We study how insulin and exercise stimulate glucose entry into muscle and how this fails in insulin resistance and type 2 diabetes. We explore intracellular 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 and transgenic mice expressing tagged GLUT4 in muscle, to test GLUT4 movement in vivo. We found that signals downstream of PI3-kinase bifurcate into activation of Akt leading to Rab8A and Rab13 activation, and Rac1 activation that controls actin filament remodelling. Orr collaborator Erik Richter (University of Copenhagen) found that mice lacking Rac1 in muscle become insulin-resistant. Mechanistically, we find that, in cells rendered insulin resistant by exposure to saturated fatty acids, GLUT4 translocation becomes defective along with alterations in Rac1 signalling to actin rather than in the Akt pathway. These studies will aid in identifying specific steps affected in muscle that curtail stimulation of glucose uptake by insulin in obesity.
Saturated fatty acids also render monocytes invasive and macrophages pro-inflammatory, producing cytokines that make muscle cells insulin-resistant. In vivo, high fat feeding of mice causes direct activation of the NOD innate immunity recognition receptors in macrophages and that contributes to whole-body insulin resistance. We documented a particular infiltration of inflammatory macrophages and neutrophils in muscles of high fat-fed mice and of obese, insulin-resistant humans, and we find that an early feature of obesity is production of infiltrating monocytes in the bone marrow. These collective findings contribute to our understanding of the link between inflammation and insulin resistance.
Finally, more recently we have investigated how glucose and insulin cross microvascular endothelial cells of capillaries, in an effort to understand the molecular underpinnings of their delivery to tissues. Defects in this step in obesity will have impact on insulin action on glucose uptake in muscle and fat cells in vivo.
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
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
Toronto, ON M5T 3L9
My clinical research focuses on:
- The impact of obesity on metabolic dysfunction
- The pathophysiology and risk factors for the development of type 2 diabetes mellitus (T2DM)
- Risk factors for cardiovascular disease in individuals with metabolic abnormalities
- 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.