Our Research Members
Associate Professor, Departments of Physiology and Medicine
Research in the Wang lab is focused on understanding the biology the pancreatic islet, im particular the regulation of islet cell secretion and function. We are also studying the biology of GLP-1, an incretin hormone released from gut cell in response to feeding. Among patients with diabetes, while the production of insulin is insufficient, release of GLP-1 is reduced. However, glucagon and glucose production is too high. While seeking a means to increase pancreatic insulin production, enhance GLP-1 action, we are also studying the signaling and molecular control of islet cell-cell interactions in regulating islet beta-cell function and glucose homeostasis during the development of diabetes. Our research is fundamental and translational, aiming at developing new therapeutic strategies that could enable patients with diabetes to permanently manage the disease and effectively avoid its associated complications.
Assistant Professor, Faculty of Kinesiology and Physical Education
Assistant Professor, Department of Anesthesia, Faculty of Medicine
Associate Scientist, Physiology and Experimental Medicine, The Hospital for Sick Children
Staff Scientist, Department of Anesthesia, The Toronto General Hospital
My research focuses on improving health and performance under extreme conditions such as respiratory and muscle diseases including cystic fibrosis, metabolic syndrome, and cancer in a pediatric population. We use advanced magnetic resonance imaging/spectroscopy techniques to help elucidate pathophysiologies of exercise intolerance in chronic disease. Recently I was involved in a project that evaluated Turner Syndrome (TS) in female adolescences. TS is associated with an increased lifetime risk of type 2 diabetes and cardiovascular disease, and we compared cardiometabolic risk factors and measures of subcutaneous, visceral adipose tissue and intra-myocellular lipid between those with TS and healthy controls. In this study we concluded that adolescent TS girls exhibit more cardiometabolic risk factors and reduced beta cell function compared with controls.
I am interested in further exploring how the presence of type 2 diabetes might contribute to exercise intolerance/reduced physical function in other chronic diseases. My research team is working to elucidate the pathophysiology of exercise intolerance in children following bone marrow transplant (BMT) – a population who is at a high risk of developing metabolic syndrome/type 2 diabetes. We plan to determine how the presence of metabolic syndrome/type 2 diabetes might influence cardiac and muscle metabolism in children post-BMT.
Assistant Professor, Department of Medicine
Scientist, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital
Director, Zebrafish Centre for Advanced Drug Discovery, St. Michael’s Hospital
The zebrafish has emerged as an important vertebrate model organism for annotation of gene function, modeling human disease and drug discovery. My lab is developing a few projects to: (1) create fluorescent zebrafish models to genetically label pancreatic beta and alpha cells, and then perform lineage specific cell ablation and study their regeneration and relationship; (2) generate novel zebrafish models for anti-diabetic compound screen. We are currently creating a reporter zebrafish strain for monitoring Phosphoenolpyruvate Carboxykinase (PEPCK) activity, a rate-limiting enzyme in gluconeogenesis. Compounds modulating PEPCK activities in zebrafish and may be developed as novel potent anti-diabetic drugs.
Professor of Ophthalmology and Vision Sciences
Director of Visual Electrophysiology, Ophthalmology; Senior Associate Scientist, Hospital for Sick Children Research Institute
One of the changes commonly observed in patients with type I Diabetes, is impaired vision. As Director of a world class pediatric visual Electrophysiology unit I have the tools to describe visual processing using the latest technologies for objective neuro-retinal assessment. My lab has made significant contributions to investigations defining the earliest neuro-marker of visual and ocular dysfunction in adolescents with Type 1 Diabetes (T1D). We found that chromatic mechanisms are disrupted at puberty in children with T1D (Invest Ophthalmol Vis Sci. 2005). Later we identified that short-wavelength retinal processing was disrupted in adolescence with T1D: McFarlane, et al. (2012), Invest Ophthalmol Vis Sci 53(2): 741-748. In later disease diabetes presents clinically as retinal lesions in isolated areas; therefore we focused our studies to early signs of damage in distinct retinal areas. Using multifocal electroretinography we found deficits in localized retinal processing: Lakhani, et al., (2010) “Insufficient long-term glycaemia control is associated with multifocal ERG defects in adolescents with Type 1 Diabetes”. Invest Ophthalmol Vis Sci. 51(10):5297-303. Recently we reported specific patterns of retinal deficits: Tan, et al., (Invest Ophthalmol Vis Sci. 2014) “Localizing Functional Damage in the Neural Retina of Adolescents and Young Adults with Type 1 Diabetes,” Invest. Ophthalmol. Vis. Sci.. 44 (4): 2432-41 We are currently the first to report localized functional disturbance on the integrity of cone photoreceptors in children with T1D using multi-model adaptive optics imaging: Tan, W., et al., Functional and Structural Cone Abnormalities in Adolescents with Type 1 Diabetes, IOVS 2012; 53: ARVO E-Abstract 371.
Professor, Departments of Medicine and Physiology
Senior Scientist, Toronto General Hospital Research Institute, University Heath Network
1 King's College Circle
Toronto, ON M5S 1A8
Our research is focussed on developing novel strategies to treat Type1 and Type 2 diabetes using multidisciplinary approaches, which combine information gained from genetic models of diabetes, genomics/proteomics, molecular biology and cell biology. Defects in pancreatic endocrine function are central factors in the pathology of diabetes. As such, we are currently investigating several avenues of research that explore pancreatic islet function in both healthy and diseased states. These include the role oxidative stress, reactive oxygen species and uncoupling proteins in the development of diabetes. We also explore the roles of membrane bound proteins like transporter, ion channels and receptors on pancreatic islet function. Another major thrust of our research is to work closely with stem cell biologists in Toronto to produce and characterize stem cell-derived beta cells for potential use in treating Type 1 diabetes.
Members of the Wheeler lab have access to state-of-art facilities at both the University of Toronto and the University Health Network at TMDT and have forged collaborations with world-class research teams working in the diabetes field. The laboratory is affiliated with the Endocrinology and Diabetes Research Group in the Department of Physiology at U of Toronto and the Banting and Best Diabetes Centre at UHN. As such the Wheeler lab is an excellent training environment for undergraduates, M.Sc. and Ph.D. candidate as well as post-doctoral fellows and residents interested in diabetes.
Associate Professor, Department of Paediatrics, Division of Endocrinology; Program Director, Paediatric Endocrinology Training Program
555 University Avenue
Toronto, ON M5G 1X8
My research focuses on clinical studies of the pathogenesis of type 1 diabetes and prevention of beta cell loss prior to the development of type 1 diabetes and at onset. I am the principal investigator for the Canadian Clinical Centre of Type 1 Diabetes TrialNet, a NIH sponsored international trial group. Our site is currently involved in multiple TrialNet studies:
- Pathway to Prevention; Natural History Study Of the Development Of Type 1 Diabetes
- Oral Insulin For Prevention Of Diabetes In Relatives At Risk For Type 1 Diabetes Mellitus
- CTLA-4 Ig (Abatacept) for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At-Risk for Type 1 Diabetes Mellitus
- Long-Term Investigative Follow-Up Study in TrialNet (LIFT)
TrialNet has 11 clinical centres across Canada.
Assistant Professor, Department of Laboratory Medicine and Pathobiology
Scientist, Division of Cellular and Molecular Biology, Toronto General Research Institute
Endocrine Pathologist, Department of Pathology, University Health Network
200 Elizabeth Street
Toronto, ON M5G 2C4
Our primary research focus is to elucidate immune mediated pathways governing obesity related insulin resistance. Obesity and its major complications, including insulin resistance, are a major global cause of morbidity and mortality, and have reached epidemic proportions. Evidence is mounting that a significant contributing cause of insulin resistance is chronic inflammation in visceral adipose tissue (VAT). This inflammation was initially thought to be driven solely by macrophages of the innate immune system attracted to dying adipocytes in fat. Recently, in collaboration with the Hospital for Sick Children, and StanfordUniversity, we have demonstrated that the adaptive immune system, including T cells, B cells and the antibodies they produce, play a significant and active role in regulating this process. This work has introduced a new “autoimmune” component to obesity related insulin resistance, and has led to new ways in thinking about metabolic disease. We continue to investigate immune mediated mechanisms in obesity and diabetes with the aim of translating our findings to help the many people afflicted by these diseases.
Professor, Department of Physiology
Research involves studies of pathological changes in the brain related to learning and memory. Specifically, diabetes can cause reduction in rate of neurogenesis in adult brain, which in turn, can lead to impaired learning and memory. Specific signals leading to impairment of neurogenesis and ways of preventing or compensating for impaired memory are under investigation.
Professor, Department of Nutritional Sciences and Department of Medicine
Graduate Coordinator, Department of Nutritional Sciences
Active Staff Member, Department of Medicine, Division of Endocrinology and Metabolism, St. Michael’s Hospital
Scientist, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital
Member, Consulting Medical Staff, Centre for Addiction and Mental Health
President, Glycemic Index Laboratories, Inc., Toronto (www.gilabs.com)
Carbohydrates in human nutrition, specifically the effects of glycemic index, sugars, starch, and dietary fiber in relation to diabetes, hyperlipidemia and colonic fermentation
Professor, Department of Medicine, Division of Endocrinology & Metabolism; and Departments of IMS, Medical Biophysics and Immunology
Head, Division of Endocrinology and Metabolism, University Health Network/Mount Sinai Hospital
Scientist, Toronto General Research Institute, University Health Network
The major research focus in the Woo laboratory is to elucidate molecular mechanisms that determine pathogenesis of insulin resistance and type 2 diabetes. Our research interests include elucidating mechanisms of islet apoptosis and survival in physiological and diabetic states. We are interested in many of the fundamental genes involved in cell survival and apoptosis such as caspases, tumour suppressors and oncogenes. Many of these fundamental genes have essential physiological roles in metabolic tissues such as liver, muscle, adipose tissue, and the pancreatic islets. Using genetically engineered mice, we examine the whole body physiology as well as take biological, biochemical and molecular approaches to define physiological roles in specific tissues, in addition to defining its potential pathogenic role in diabetes. These approaches to clarify tissue-specific molecular mechanisms have wide implications for treatment of both type 1 and type 2 diabetes.
Department of Medical Biophysics
Director, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Our laboratory is primarily interested in the abrogation of signal transduction pathways in human disease, in particular the phosphatidylinositol 3′ kinase pathway and the Wnt pathway. Both are implicated in cancer and diabetes. We are studying several protein kinase components of these pathways, such as Protein Kinase B (PKB/Akt), Serum and Glucocorticoid-inducible Kinase 3 (SGK3) and Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is associated with Alzheimer’s Disease, bipolar disorder and type II diabetes. There are two mammalian genes for GSK-3, termed alpha and beta and we have generated both conventional and tissue-specific knockout mice strains of each. For example, we have generated mice that specifically lack GSK-3beta in either skeletal muscle and have characterized the insulin and glucose tolerances of these animals. GSK-3 is inhibited by insulin signalling and thus the knockouts are providing insight into the utility of GSK-3 inhibitors as sensitizers for insulin-resistant patients. We are also identifying novel targets for GSK-3 (and other protein kinases) which will help us understand the molecular mechanisms by which GSK-3 influences blood glucose responses.
Professor, Department of Molecular Genetics
Senior Investigator, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
600 University Ave., Room 1078
Toronto, ON M5S 1X5
Phone: 416-586-4800 x2791
Study of mechanisms underlying complications of diabetes, in particular kidney fibrosis.
Professor, Leslie Dan Faculty of Pharmacy
Advanced Pharmaceutics & Drug Delivery Laboratory
Advanced pharmaceutics and drug delivery. Our research interests and activities related to diabetes treatment include microencapsulation of enzymes, therapeutic hormones and polypeptides; artificial islet cells; nanomaterials such as bio-inorganic, polymer-metal and polymer-lipid hybrid nanoparticles and nanocomposite membranes; nanoparticulate contrast agents and fluorophores for in vitro/in vivo imaging; ROS-regulating systems; “intelligent” drug delivery systems for self-regulated drug delivery; nanotechnology-enabled glucose-responsive closed-loop insulin delivery implants for diabetic research animals and for clinical treatment.