Congratulations to the DRC 2014 Award Recipients!
Pilot and Feasibility Award
Shreeram Akilesh, MD, PhD, Acting Instructor
Department of Pathology
Project Title: Regulatory Genomics of Reversal of Diabetic Nephropathy
Diabetic nephropathy is the leading cause of end-stage kidney disease and dialysis in the United States. Within the kidney, the filtration barrier and especially its specialized epithelial cell, the podocyte, is particularly susceptible to diabetes-induced damage. The BTBR ob/ob mouse model of type 2 diabetes accurately recapitulates the progressive podocyte loss that is thought to underlie diabetic nephropathy. Interestingly, leptin administration reverses kidney injury and restores podocyte numbers in this model. Dr. Akilesh will use advanced genomic techniques (DNase-seq) and bioinformatic approaches to dissect the genomic regulation that underlies podocyte injury and regeneration in the BTBR ob/ob mouse model of diabetes. These studies will provide insights into mechanisms and approaches to reverse diabetic kidney injury in humans.
Laura den Hartigh, PhD, Research Assistant Professor
Department of Medicine
Project Title: 10, 12 CLA promotes insulin resistance by antagonizing PPARγ
10,12 CLA is a naturally occurring dietary trans fatty acid reported to promote weight loss. Despite carrying significantly less fat than control mice, mice consuming 10,12 CLA do not show improved glucose metabolism. PPARγ is abundantly expressed in adipose tissue, where it contributes to whole-body glucose homeostasis. Congruent with the loss of fat mass, 10,12 CLA-supplemented mice have reduced PPARγ gene expression. We therefore hypothesize that 10,12 CLA contributes to insulin resistance by attenuating PPARγ activity. Dr. den Hartigh will examine cellular mechanisms by which 10,12 CLA could attenuate PPARγ expression and/or activity, and determine if a potent PPARγ agonist, rosiglitazone, restores insulin sensitivity in mice.
Wang Wang, MD, PhD, Assistant Professor
Department of Anesthesiology and Pain Medicine
Project Title: Mechanistic coupling between obesity and mitochondrial oxidative stress in diabetic cardiomyopathy
Metabolic syndrome, featured by obesity and diabetes, is an independent risk factor for cardiovascular disease, including ischemic heart disease and diabetic cardiomyopathy. The goal of this Pilot and Feasibility project is to test the hypothesis that high fatty acid supply, often seen in obese patients, stimulates fatty acid oxidation, fuels mitochondrial respiration-coupled reactive oxygen species(ROS) production and over time leads to oxidative stress and insulin resistance in the heart. Dr. Wang will use state-of-the-art confocal imaging approaches combined with specific ROS indicators, biochemical measurements, transgenic mice and obesity mouse models to systematically investigate the causal role of high fatty acid oxidation in mitochondrial-derived ROS production in the cardiac myocytes. The results of this study will provide new insights into the causal link between obesity and diabetic cardiomyopathy.
Samuel and Althea Stroum Fellowship Award
Valerie Wall, Graduate Student (Mentor: Karin Bornfeldt)
Department of Pathology
Project Title: Glucose specific effects on vascular smooth muscle cells in mouse models of accelerated atherosclerosis
Increased blood glucose has been linked to accelerated atherosclerosis in humans and in animal models. Phenotypic changes in endothelial cells, smooth muscle cells and macrophages occur during the process of lesion initiation and progression. However, which of these cell types are directly influenced by high blood glucose remains to be determined. I am using a model that increases glucose uptake in select cell types to test which of these cell types are directly altered by glucose and contribute to vascular disease in vivo. Preliminary data indicates that increased glucose uptake in vascular smooth muscle cells, but not in macrophages accelerates atherosclerosis.