Our Research Members

Deficiencies in maternal diet or exposure to environmental toxins during pregnancy can affect developmental trajectories and program postnatal disease propensity in the progeny, including metabolic disorders and diabetes. The mechanisms that underlie the environmental modulation of developmental and stem cell biology remain largely unknown. We are investigating the impact of a variety of environmental stressors during gestation on epigenetic states in fetal cells and physiological outcomes into adulthood and across generations. For example, we have implemented mouse models wherein nutritional deficits during pregnancy induce glucose intolerance and insulin resistance in the progeny.  We are dissecting the underlying molecular and cellular mechanisms using cutting-edge epigenomics approaches. We anticipate that this knowledge may reveal avenues to both prevent developmental programming of diabetes from occurring in the first place as well as to epigenetically reverse it after the disease manifests.

My research program focuses on the pathophysiology and treatment of type 2 diabetes (T2DM), with a particular interest in the potential reversibility of pancreatic beta-cell dysfunction early in the course of diabetes. In this context, our research group is conducting a series of innovative clinical trials evaluating novel therapeutic strategies for the preservation of beta-cell function in early T2DM, including the CIHR-funded RESET IT Trial and PREVAIL Trial. In addition, our research program has highlighted the concept that a women’s gluco-regulatory response to the metabolic challenge posed by pregnancy can provide unique insight into her future risk of T2DM and cardiovascular disease later in life. This concept is being studied with CIHR-funded prospective observational cohorts in Toronto and China.

Interaction between pancreatic islets and vascular endothelial cells is necessary for the maintenance of beta-cell mass and function. Aside from acting as a conduit for molecular oxygen, vascular endothelial cells in vivo secrete the majority of islet extracellular matrix (ECM). This ECM likely provides a permissive signal for beta-cell proliferation, contributing to the coordinated hyperplasia of these tissues during the early stages of Type 2 diabetes. This ECM also provides a reservoir for heparin binding growth factors that further modulate this hyperplasia, including fibroblast growth factor (FGF) and vascular endothelial growth factor-A (VEGF-A). We hypothesize that communication between beta-cells and vascular endothelial cells directs the proliferation and function of both tissues.

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.