Our Research Members

Our research is focused 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 understanding the roles of membrane bound proteins like transporters, ion channels and receptors on pancreatic islet function. We also explore the therapeutic effects of prescription drugs and their metabolites to enhance pancreatic regeneration and treat diabetes. Another major thrust of our research involves utilizing high throughput metabolomics and lipidomics approaches to uncover the underlying pathophysiology of Gestational Diabetes and its transition to Type 2 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 the University of Toronto and the Banting & Best Diabetes Centre, University of Toronto. 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.

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
• 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)
• Hydroxychloroquine for Prevention of Abnormal Glucose Tolerance and Diabetes in Individuals At-Risk for Type 1 Diabetes Mellitus

TrialNet has 11 clinical centres across Canada

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.

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.

The major research focus in the Woo laboratory is to elucidate molecular mechanisms that determine pathogenesis of insulin resistance, type 2 diabetes and related diseases including atherosclerosis and NAFLD. We are interested in many of the fundamental genes involved in cell survival and differentiation such as caspases, tumour suppressors and oncogenes. Many of these fundamental genes have unique physiological roles in metabolic tissues such as liver, muscle, adipose tissue, and the pancreatic islets. Using genetic or pharmacologic approaches, we examine the whole body physiology as well as take biological, biochemical and molecular approaches to define molecular physiological roles in specific tissues, in addition to defining its potential pathogenic roles in diabetes and related diseases.

Study of mechanisms underlying complications of diabetes, in particular kidney fibrosis.

Advanced pharmaceutics and drug delivery. Our research interests and activities related to diabetes treatment include microencapsulation of enzymes, formulation and stabilization of therapeutic hormones and polypeptides; artificial islet cells; ROS-attenuating 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; and glucose-responsive glucagon delivery via composite microneedle patch for prevention of hypoglycemia in diabetes.

Our primary focus is in single molecule biophysics and specifically the interaction between biomolecules, including membrane receptors. Our primary research tools are single molecule microscopies (confocal / TIRF / atomic force) coupled with high-resolution infrared and fluorescence spectroscopies. We are motivated by a keen interest in the functional integration of these techniques to enable single molecule imaging in live cells. Our past efforts have included direct imaging of isolated insulin receptors in model membranes, single molecule force spectroscopy of insulin self-association, and mapping of glucacon fibril formation, and characterization of insulin crystallization by atomic force microscopy.

My research interests lie in the role of patient and clinician behaviour change in knowledge translation. I am particularly interested in the development of innovative strategies for continuing professional development and patient education in chronic disease management, specifically diabetes care. My projects include the role of interactive self-management websites, order sets, computer-based simulators and interprofessional workshops on knowledge, behavior change, clinical and psychological outcomes. My additional research specialties include endocrinology and medical education. 

My lab, in collaboration with Dr. Minna Woo, has demonstrated the effect of unphosphorylated, constitutive active form of the tumor suppressor pRb on pancreatic islet homeostasis. We found that constitutive active pRb knocking mice, Rb∆K7, exhibit pancreatic beta cell degeneration, senescence and diabetes. We also showed that vitamin C, an agonist of TET enzymes, attenuated senescence and diabetes in these mice (EMBO J, 2022).

We are currently exploring improved strategies to reduce senescence and increase regeneration of pancreatic beta cells (with Drs. M. Woo and D. Winer). In collaboration with Drs. Herbert Gaisano and Gary Bader, we’re analyzing pancreatic islets from these diabetic mice by snRNA-seq/ATAC-seq and have identified targetable alterations.

Dr. Zinman was involved in studies evaluating metabolic and pharmacologic interventions to prevent diabetes complications, diabetes in aboriginal communities, and evaluation of new therapies for Type 1 and 2 Diabetes.