Our Research Members

The Roger’s lab uses progenitor cells and human pluripotent stem cells as a basis for developing cell based therapies for the treatment of Diabetic symptoms. We are investigating the wound healing properties of blood cells and mesenchymal cells in a model of Peripheral Vascular Disease (PVD) and Diabetic skin wounds. My lab has demonstrated that these cells have strong paracrine signaling that can reduce inflammation and apoptosis while promoting angiogenesis. Together, this results in superior tissue repair.

The Rogers’ lab is also focused on studying diabetic nephropathy through the development of 3D culture systems. Using decellularized kidneys from mouse and porcine as a substrate we can interrogate the role of the ECM in kidney regeneration. Human iPSC made from blood or cells in the urine are differentiated into renal progenitor cells and applied to the acellular ECM. This project allows for investigating the role of stem cells and their niche. By using decellularized kidney from healthy and diabetic mice (or humans) coupled with kidney progenitor and mature cells from healthy and diabetic sources, we can determine if diabetes is affecting the niche or the progenitor cells. 

The goal of my research is to inform the prevention of type 2 diabetes in the population. At the Population Health Analytics Laboratory, my research focusses on the use of advanced epidemiologic and biostatical approaches on large population-based data to inform public health activities targeted at reducing type 2 diabetes and obesity. I specialize in the development of population risk tools and I have led methodological advances in the new field of risk algorithms applied to the population setting. I developed the Diabetes Population Risk Tool (DPoRT), which is the only tool built to inform population intervention strategies for diabetes. This work is recognized as a novel way to inform to diabetes preventions strategies and is currently being used by policymakers in Canada. I have also led the largest study estimating diabetes-attributable health care costs as well as the burden of undiagnosed diabetes in Canada. I am expanding this research to understand how persons living with type 2 diabetes accumulate chronic conditions over their life course and elucidating what factors contribute to mortality outcomes.

Dr. Hannes Röst is an Assistant Professor at the Donnelly Centre at the University of Toronto, the Canada Research Chair in Computational Mass Spectrometry and Personalized Medicine, Co-Director of the Donnelly Mass Spectrometry Facility and is a dual-appointed Assistant Professor at the University of Toronto in the Department of Molecular Genetics (Temerty Faculty of Medicine) and the Department of Computer Science (Faculty of Arts & Science).

Dr. Röst co-developed SWATH-MS and invented the OpenSWATH algorithm, the first software for targeted analysis of DIA data, which matched the quantitative performance of previous targeted methods, while increasing throughput one to two orders of magnitude. During his postdoctoral work at Stanford in the laboratory of Mike Snyder, he successfully applied mass spectrometry to profile proteins and metabolites using longitudinal, personalized medicine studies to understand population variation and disease progression in a type II diabetes cohort. He developed the TRIC algorithm, the first cross-run alignment algorithm for targeted proteomics data. Dr. Röst has developed statistical approaches for multi-omics data in personalized medicine based on mixed effect linear models to statistically remove the personalized baseline level for each analyte and compute perturbation-induced changes.

The research group of Dr. Röst is applying state-of-the-art multi-omics analyses approaches to better understand the early development of type II diabetes. To this end, he is using a cohort of pre-diabetic patients that are followed during a period of over 7 years and has worked in a collaboration to analyze data from the SWIFT cohort, a gestational diabetes cohort with follow-up time of over 8 years. His group uses proteomics, metabolomics and lipidomics techniques to better understand and predict development of diabetes on a molecular level.

The prevalence of obesity is increasing worldwide, as is the prevalence of obesity-related co-morbidity. Obesity is associated with an increased risk of developing insulin resistance and Type II diabetes (T2D). A universal observation in both humans and rodents is that impaired insulin secretion in is caused by a marked increase in pancreatic beta-cell destruction that outweighs the rate of beta-cell replication and renewal. Currently, the factors that instigate an increased rate of beta-cell death during the pathogenesis of T2D are not fully understood. Our lab has identified novel chromatin associated factors that serve to regulate pancreatic islet regeneration and glucose homeostasis.  Research in the Rozakis lab is focused on understanding how these factors  influence the epigenetic landscape in metabolic tissues under normal and pathophysiological conditions. Moreover, using a combination of biochemical, proteomic, and transgenic animals models we will characterize epigenetic events that influence immune modulatory activities in islets and protect against inflammatory demise of pancreatic beta-cells.

Research in my laboratory at the University of Toronto is focused on cellular and molecular mechanisms responsible for the development of diabetic nephropathy. In particular we study the role of the renin angiotensin system (RAS) in diabetic nephropathy and the link between the RAS, obesity, and activation of NADPH oxidase. We utilize transgenic mice in our approach and have combined whole animal studies with cell culture experiments to define cellular mechanisms of injury. We are currently studying mice with deletions in the genes for ACE2, p47, and adiponectin. Our laboratory also collaborates with investigators in the Human Physiology Laboratory at the University Health Network, Mount SinaiHospital, and the Hospital for Sick Children on studies of kidney function and urine proteomics in humans with diabetic nephropathy.

My lab is interested in understanding how human cells respond to extracellular cues to maintain and ensure their function and survival. One central focus is to study how the pancreatic beta cell converts feeding cues into signals leading to insulin production and secretion. We use high-throughput functional screens to identify novel players involved in different cell-signaling pathways, including human pancreatic beta cell proliferation and those involved in the maintenance of mitochondria, critical subcellular organelles essential for cell function and survival. In addition to Type 1 and Type 2 diabetes, our work impacts upon cancer and neurodegeneration.

Biomaterials and tissue engineering. Delivery of islets and pseudo-islets into vascularized, subcutaneous tissue, including microencapsulation and immune modulation using dendritic cells.

My research focus is on the quality of and outcomes of diabetes care. Much of this work is done using linkage of large health care administrative data bases. My three main areas of interest are: a) the influence of different care models on diabetes quality and outcomes, b) gestational diabetes care and outcomes, and c) diabetes in vulnerable populations, including ethnic, immigrant and indigenous communities.

Dr. Shulman’s research program is focused on developing and evaluating health services interventions to improve the health and quality of care for youth living with diabetes. Areas of focus include transition to adult care, preventing DKA at diabetes diagnosis, and reducing socioeconomic disparities in care and outcomes. She is particularly interested in developing and evaluating interventions that leverage existing population-level administrative datasets to inform health system change. Currently, an ongoing multi-site study, KiT (Keeping in Touch), has developed and is testing a text message-based algorithm to deliver just-in-time personalized transition education that will help young adults transition to adult care. In collaboration with the Canadian Pediatric Endocrine Group (CPEG), Dr. Shulman is leading an initiative to co-develop a national strategy to prevent DKA at diabetes diagnosis.

My research program continues to strive to identify and investigate important diet and disease questions in the area of cardiometabolic risk and diabetes. We use knowledge synthesis techniques (systematic reviews and meta-analyses) and randomized controlled trials to address the need for high quality data to inform clinical practice guidelines and public health policy, as well as guide the design of future trials. Clinical practice guidelines and public health policy are moving away from the more traditional macronutrient-centric dietary approaches (“low-fat”, “low-carb”, “high protein”) to more food and dietary pattern based approaches. I have helped to initiate and steer this change in the 2013 guidelines of the Canadian Diabetes Association (CDA) and the upcoming 2015 guidelines of the European Association for the study of diabetes (EASD). My research program has attempted to keep up with this modernization, as reflected in the main ongoing food and dietary pattern based foci of my research program: sugars (fructose, sucrose, high fructose corn syrup), dietary pulses (beans, peas, chickpeas, lentils), tree nuts, and portfolio and low glycemic index dietary patterns.

I am a Transplant Nephrologist in the Division of Nephrology at the Toronto General Hospital with additional training in diabetes care in transplant recipients and pancreas transplantation as a treatment option for patients with Type 1 diabetes. In collaboration with Dr. David Cherney, I am currently a site investigator/Co-Investigator at UHN for two clinical trials: 1) DAPA CKD: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease and 2) A double-blind, placebo controlled, cross-over renal mechanistic trial to assess the effect of adding empagliflozin versus placebo on renal hyperfiltration in patients with type 1 diabetes on a background of the angiotensin converting enzyme inhibitor (ACEi) Ramipril: BETWEEN study. I also have a research interest in Pancreas Transplantation. I am currently a Co-Investigator (PI: Dr. Cherney, Co-I: Dr. Kim, Dr. Cattral) on a pilot study evaluating the impact of pancreas transplantation on the complications of Type 1diabetes (BBDC Sun Life Financial Pilot and Feasibility Grant) and have published clinical outcomes research in patients with type 1 diabetes with pancreatic transplants. I also have interest in understanding the pathogenesis of recurrent diabetic kidney disease (DKD) in the kidney allograft and therapies for DKD in the transplant population. Our group has recently published our experience describing the safety and efficacy of SGLT2 inhibitors in a group of kidney and kidney-pancreas transplant recipients.

Diabetes, lipoproteins and atherosclerosis.

Research interest is in studying the role of ion channels (K(ATP) and TRPM2, etc.) in diabetes and stroke in diabetes, neuroprotection, and drug development, using in-vivo animal models of human diseases in combination with genomic analyses, advanced imaging, electrophysiology, and functional and behavioral assessments.

Publication related to diabetes research: Cerebrovascular safety of sulfonylureas: the role of K(ATP) channels in neuroprotection and the risk of stroke in patients with type 2 diabetes. Diabetes. 2016, 65(9): 2795-2809

My lab is studying Obesity, Metabolism and Diabetes at The Hospital for Sick Children. Our research focus includes:
1) patho-physiology of adipose tissue expansion and its causal role in metabolic defect and diabetes
2) identification of adipocyte precursor cells and its metabolic function by using mouse model

My research examines neuroendorcrine contributions to mood and cognitive symptoms in type 2 diabetes. My lab conducts clinial studies, primarily of people with type 2 diabetes undertaking exercise-based rehabilitation and education interventions. We have a particular interest in the roles of cerebrovascular disease (including stroke and microagniopathy) in the effects of type 2 diabetes on the brain. We use neuroimaging, metabolomic and neurocognitive techniques.

The search for putative precursor cells within the pancreas has been a focus of extensive research. Adult mouse Pancreas-derived Multipotent Precursor (PMP) cells, possessing the intriguing capacity to generate cross-germ layer progeny in the pancreatic and neural lineages, have been identified. Here, genetic lineage-labelling was used to exclude the neural crest as the developmental source of PMPs. Notably, we demonstrate that the PMP cell expresses insulin in vivo, providing reconciliation with reports that new adult b cells are formed exclusively by self-replication. Further, PMP cells were shown to exist within adult human islet tissue, each capable of extensive proliferation, self-renewal, and generation of multiple differentiated pancreatic and neural cell types. Finally, the newly generated human b cell progeny were found to display regulated insulin secretion. These findings demonstrate that the adult mammalian pancreas contains a population of insulin+ multipotent stem cells, capable of contributing to the neural and pancreatic lineages.

My research program focuses on cardiometabolic disease and diabetes-related co-morbidities. As the Chair of the CardioLink Clinical Trials platform, I am conducting a number of clinical trials in diabetes and its complications. The first of these trials, EMPA-Heart, seeks to uncover the mechanism underlying the cardioprotective effects of the SGLT2 inhibitor, empagliflozin, that was reported in the EMPA-REG Outcome study. This trial is in the late stages of recruitment and will report primary outcomes in 2018. The NEWTON CABG trial will assess whether blockade of the PCSK9 receptor in individuals will diabetes can reduce the risk of future cardiac events after bypass surgery. In the ENABLE-Chiropody trial, persons with diabetes undergoing hemodialysis will undergo a chiropody-based intensive, structured, and evidence-based care program with the aim of lowering the incidence and progression of diabetic foot ulcers and amputations. This initiative is fully supported by a partnership with Diabetes Action Canada which is part of the CIHR-SPOR network. In addition, I oversee a dynamic research lab in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital which has a special interest in the role of SGLT2 inhibitors as a potential modulator of endothelial function and atherosclerotic vascular disease. Finally, I am a national lead/steering committee member on three SGLT2 inhibitor trials that are evaluating the impact of this class of drugs on heart failure.

Viscous Dietary Fiber Blend

This blend maximizes viscosity as a driver of physiological effectiveness in the management of diabetes and reduction of blood lipids. Dr. Vuksan holds Canadian & USA patents for this discovery. His research on fiber blend has attracted the attention of the food industry, and the product is now commercially available worldwide.

Salvia Hispanica L.

The consumption of this ancient Aztec seeds high omega-3/fiber rich, improved conventional and novel risk factors for cardiovascular disease in those with diabetes. Dr. Vuksan’s studies were the first to demonstrate health benefits of these seeds in humans, gaining the attention internationally of the research community and popular press. Economic analysis on exports by main producers of Salvia Hispanica, Mexico, Argentina and Australia, show a major surge in export of the seeds coinciding with his publications in 2007/2010. His research has thus ignited significant economic benefits to countries producing the seeds and the local farmers have led to increased human consumption worldwide.

Ginseng

Ginseng was hardly known for its metabolic benefits in humans until Dr. Vuksan’s studies in early 2000. His group was the first to demonstrate potential hypoglycaemic efficacy and safety of ginseng. His investigations of the potential of medicinal herbs and ginseng in particular have received international recognitions.

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.