Our Research Members

Lipid and Lipoprotein Disorders in Insulin Resistant States, Metabolic Syndrome and Type 2 Diabetes; Incretin Regulation of Intestinal Lipid and Lipoprotein Metabolism. Current areas of interest and active research in our laboratory include: Mechanistic studies of the link between diabetes and the increased risk of cardiovascular disease; Mechanisms of metabolic dyslipidemia in insulin resistant states; Regulation of Intestinal Lipid and Lipoprotein Metabolism by Gut Peptides; GLP-1 and GLP-2 signaling in the intesteine; Molecular biology of atherogenic lipoproteins and apolipoprotein B and involvement in the development of atherosclerosis; Mechanistic links between childhood obesity, insulin resistance, and the risk of development of premature atherosclerosis; mechanisms of action of hypolipidemic drugs at the cellular and molecular level.

Despite current treatments, people with diabetes continue to be affected by the long-term consequences of the disease. These long-term consequences are called complications and they include eye disease, kidney disease, nerve disease and heart disease. Kidney disease due to diabetes is the most common cause of kidney failure requiring treatment with dialysis or kidney transplantation and people with kidney disease are much more likely to also suffer from heart disease. Our research program is focused on the discovery and development of new treatments for kidney disease and heart failure, especially kidney disease or heart failure caused by diabetes; and on improving the lives of people living with Type 1 diabetes today. To help us achieve these goals we have three research strands:
1) Understanding the roles that epigenetic processes play in kidney disease and heart failure. 2) Repurposing existing therapies and exploration of the glucose-independent effects of diabetes treatments. 3) Learning about the experiences of young adults living with Type 1 diabetes.

Dr. Mahavir Agarwal is a psychiatrist by training who joined the University of Toronto Faculty in the spring of 2019. He is staff psychiatrist and Clinician-Scientist at the Centre for Addiction and Mental Health (CAMH) where he runs the Mental Health and Metabolism Clinic and the Clozapine Clinic in the Schizophrenia Division. His research interests lie in understanding the pathophysiology of metabolic and cognitive disturbances observed in schizophrenia, especially the severely elevated risk of obesity and type 2 diabetes observed in this population and the cognitive worsening that results from poor metabolic health. He is focusing on the role of insulin resistance in the brain in determining cognition and metabolic risk. To this end, he employs a multi-disciplinary approach to studying metabolic and cognitive outcomes using multi-modality neuroimaging, measures of cognitive functioning, and glucose metabolism (i.e. euglycemic pancreatic clamps and the oral glucose tolerance test).

Dr Johane Allard is a Gastroenterologist and a Professor of Medicine, cross-appointed to the Department of Nutritional Sciences, the Institute of Medical Sciences and the School of Graduated Studies of the University of Toronto. She is a Senior Scientist at the Toronto General Research Institute. Her research interest is nutrition related to obesity, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), malnutrition and nutrition support. She conducted previous studies on dietary intakes, gene expression, fatty acid composition, micronutrients and oxidative stress. More recently, she focused on NAFLD. 

Her group was the first to describe altered intestinal microbiota in patients with biopsy proven NASH compared to healthy controls. Following up on these findings, Dr. Allard with the bariatric surgery team at the University Health Network was awarded a CIHR operating grant examining the “Role of intestinal microbiota in NAFLD pre and post bariatric surgery.” Initial analysis showed that those with NASH had higher liver enzymes, insulin resistance, and presence of diabetes compared to those with a normal liver. Additionally, with bariatric surgery, there was a significant improvement in liver histology, biochemical, and clinical parameters but about 19% of patients had persisting NAFLD despite similar weight loss. These patients had less improvement in waist circumference and glycemic control. Studies on the intestinal microbiota and metabolites are pending.

Dr Allard is also the principal investigator of a CIHR team grant with Dr Gaisano as co-PI. She is heading a group of clinical/translational researchers and basic scientists, aiming at “Exploiting the therapeutic effects of the fecal microbiome in bariatric care”. The goals of the team grant are:

1. To track the changes in the intestinal microbiome in morbidly obese patients undergoing bariatric surgery and determine the relationship with improvement in insulin resistance, diabetes, and weight loss.
2. To test the effect of fecal microbiota transplant of lean donors into morbidly obese patients on insulin resistance, body weight and NAFLD.
3. To determine if fecal microbiota transplant from morbidly obese patients post-bariatric surgery can improve the in vivo parameters of insulin resistance, glucose-induced insulin synthesis, and obesity/weight loss in germ-free mice. The objective is to determine the specific candidate microbial species or genes in the mice that account for these beneficial effects.

Our laboratory performs both animal and human (all age groups) experiments. The main focus of research in my lab includes food intake regulation and glycemia; carbohydrates, sweeteners, appetite and health; proteins, amino acids and food intake; dietary control of peptide hormone and neurotransmitter metabolism; and food composition, dietary status and chronic disease. My laboratory is committed to elucidating the dietary determinants and mechanisms of glycemic control and food intake. Recent study topics include: (1) investigating the effect of milk products and novel milk products on metabolic control (glycemia and gut hormones), satiety and food intake, (2) the effect of pulses and pulse ingredients on glycemic response, subjective appetite, food intake and gut hormones, and (3) investigating the effects of high vitamin intake during pregnancy on neurotransmitter gene expression and their relationship with fat mass and insulin resistance in the Wistar rat offspring at birth, at weaning and beyond.

My research is focused on understanding how morphogen signalling pathways control developmental processes, including the differentiation of human pluripotent stem cells into diverse tissues.  Stem cell-based therapies for a variety of disorders are being explored including the use of beta cells as a cell replacement therapy for diabetics.  Protocols to produce pancreatic beta cells from human pluripotent stem cells have been established, but these beta cells are fetal-like and immature, requiring long term (months) in vivo implantation to acquire a more adult phenotype. Several studies indicate that the vascular niche is critical in this maturation process. We recently developed a proprietary microfluidic device that enables the in vitro production of perfusable vasculature.   We are currently exploring whether and how introduction of islet specific vasculature can enhance the efficient production of stem cell derived beta cells and promote their survival, function and maturation.