Current Funding Awardees

Megan Capozzi Ph.D.
Research Assistant Professor
Department of Medicine
Division of Metabolism, Endocrinology and Nutrition

Hepatic Glycogen Control of Insulin and Glucagon Activity
Hepatic glycogen is an important source of energy, storing glucose in response to insulin and mobilizing glucose in response to glucagon. Yet, glycogen levels are decreased in patients with diabetes and preclinical efforts to manipulate hepatic glycogen show promise for treatment of diabetes. In this project, we will test the hypothesis that the hepatic glycogen level will affect insulin and glucagon levels and/or hepatic post-receptor signaling to control its own repletion in physiology and pharmacology. We will use mouse models of altered hepatic glycogen storage to assess insulin and glucagon levels and hepatic action in response to meal nutrients and incretin agonism. Findings from this study will provide a basis in future studies to understand how to logically manipulate glycogen to recover the altered energy homeostasis that occurs in metabolic disease.

Huu Hien Huynh, Pharm.D., Ph.D.
Acting Instructor
Department of Laboratory Medicine & Pathology

Assessment of Type III Collagen Turnover in Diabetic Kidney Disease
Diabetic kidney disease (DKD) is a common complication of diabetes that can result in injury to kidney tubular epithelial cells and their microenvironment through stimulation of proinflammatory and profibrotic pathways. About 30% of individuals with diabetes experience kidney disease, which is the major cause of kidney failure, leading to a significantly elevated risk of premature death. Late stages of DKD are marked by interstitial fibrosis with type III collagen being the most abundant collagen in the interstitial space. The goal of this project is to characterize the balance between type III collagen deposition and remodeling across the spectrum of disease by accurately measuring three different regions of type III procollagen using liquid chromatography coupled to tandem mass spectrometry. Assessing the balance of type III collagen deposition/degradation during the development of kidney fibrosis may help to identify patients with deteriorating kidney function, which could improve current strategies for diagnosis, prognosis, and therapeutic monitoring

Devasena Ponnalagu, Ph.D.
Assistant Student
Department of Pharmacology

Unravel Mechanistic Role of Chloride Intracellular Channel 4 (CLIC4) in Metabolic Disorders
Metabolic disorders like obesity are a global health concern. In addition to genetic defects, consumption of energy-rich food is a major contributor to these disorders. Cation channels have been demonstrated to regulate High-Fat Diet (HFD) induced obesity by modulating adipocyte proliferation and differentiation, and mitochondrial function, respectively. Yet, the role of equally important chloride channels in regulating metabolic disorders remains elusive. Our exciting preliminary results suggest a significant role of one of the paralogs of chloride intracellular channel (CLIC) proteins CLIC4, in metabolic changes associated with HFD consumption. However, key questions about (a) the mechanism by which CLIC4 absence regulates metabolic phenotypes, and (b) the major metabolic tissues and pathways affected by CLIC4 ablation post-HFD consumption are unknown. This proposal aims to address these queries by performing a comprehensive analysis of metabolic function to uncover the effect of CLIC4 on body composition and energy balance upon HFD consumption (Aim 1). In Aim 2, we will identify the mechanistic role of CLIC4 in affecting the physiology of adipose tissue and liver upon HFD consumption. Overall, this proposal will open new avenues of exploration that will link abnormal chloride homeostasis and metabolic disorders.