Our Research Members

My research uses epidemiological and health services research methods to study determinants of outcomes in type 1 diabetes, using large data sources such as administrative health care and Electronic Medical Record (EMR) databases. Specific interests include evaluation of type 1 diabetes care and outcomes at a population level, and pharmacoepidemiology

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.

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.