Department: Physiology, University of Toronto
1. Current Major Research Interests
The Lewis lab performs whole body, integrative, physiological studies in humans. The major line of research interest of Dr. Lewis' laboratory is:
a) Determining the mechanism of intestinal and hepatic lipoprotein overproduction in insulin resistance and Type 2 diabetes. We perform studies in humans, attempting to determine the molecular mechanisms whereby the liver and intestine overproduce lipoproteins in these conditions. We are currently examining the regulation of intestinal and hepatic lipoprotein particle production by hormones and inflammatory factors in humans, particularly as they pertain to the insulin resistant condition.
b) The effect of free fatty acids on pancreatic beta cell secretory function. In a series of in vivo experiments in humans we have demonstrated 'lipotoxicity' from elevated plasma free fatty acids on pancreatic beta cell function. We are currently examining the role of oxidant stress, ER stress and inflammation in mediating the deleterious effects of lipids on beta cell function.
2. Previous and Currently Inactive Major Research Interests
a) Mechanism of HDL lowering in insulin resistant and hypertriglyceridemic states.
b) In vivo studies in genetically altered mice investigating the mechanisms of insulin resistance, impairment of pancreatic beta cell function and mechanism of action of pharmacological agents.