Researchers within the Diabetes, Obesity and Metabolism Research Focus Area have expertise in studying bile acid, glucose, lipid and lipoprotein metabolism.
Yanqiao Zhang, M.D., Director
Dr. Zhang’s group focuses on understanding how bile acid, lipid or glucose homeostasis is maintained under normal and disease conditions. Dysregulation of these metabolic pathways may lead to a variety of metabolic diseases. His group studies nuclear hormone receptors, non coding RNAs, activating transcription factor 3, etc. His studies are highly relevant to diabetes, obesity, non-alcoholic fatty liver disease and atherosclerosis. Dr. Zhang hopes his research will lead to identification of novel pathogenic mechanisms and/or therapeutics for these common metabolic diseases.
John Chiang, Ph.D.
The Chiang lab studies bile acid synthesis in the liver. His laboratory first purified cholesterol 7-alpha-hydroxylase (CYP7A1), cloned the gene encoding CYP7A1, and studied regulation of the CYP7A1 gene. His current research projects are focused on how bile acid-based regulation of glucose, lipid and energy metabolism is disturbed in obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD), the latter of which affects approximately 30% of the US population, and how bile acids can be utilized for therapeutic treatments. His laboratory created several mouse models to study bile acid metabolism, liver fibrosis, and NAFLD. His lab utilizes advanced high-throughput techniques like RNA-sequencing to monitor changes in genes and to identify the gut microbes that are involved in bile acid signaling; this information can then be applied toward the potential development of drugs targeting obesity, diabetes, and liver diseases.
Jessica Ferrell, Ph.D.
Dr. Ferrell is interested in the gut-brain axis, and how daily circadian rhythms originating from the brain control liver metabolism, specifically with respect to bile acid homeostasis. Circadian rhythm disruption (for example, shift work, sleep deprivation, and even chronic jet lag) negatively affects human health and contributes to the development of obesity and diabetes. Dr. Ferrell utilizes sleep deprivation and restricted feeding in mice to model shift work; this introduces disruption to the peripheral circadian system which is then reflected in the liver and gut in the form of altered bile acid homeostasis, dysregulation of lipids, and metabolic syndrome. Dr. Ferrell is also interested in the development and progression of liver fibrosis and utilizes several dietary models to study this disease.
James Hardwick, Ph.D.
Dr. Hardwick’s laboratory focus on understanding the role of inflammation and lipid metabolism in diabetes, obesity and liver disease. His group has identified, isolated and characterized several cytochrome P450 enzymes that function in the metabolism and elimination of drugs, environmental toxins, and carcinogens. Understanding individual susceptibility to the adverse effects of drugs, toxin or carcinogens is due to individual polymorphic expression of different cytochrome P450 enzymes. Identification of polymorphic variants of cytochrome P450 enzymes that increase or decrease drug effectiveness or toxicity defines the future of precision medicine. Currently, Dr. Hardwick’s laboratory is focused on understanding how members of the fatty acid omega hydroxylase gene family (CYP4) initiate fatty liver and hepatitis during the progression of both alcoholic and non-alcoholic fatty liver disease to liver cirrhosis and cancer.
Takhar Kasumov, Ph.D.
Dr. Kasumov’s research has been focused on developing new high-throughput mass spectrometry-based technologies to understand dysregulated lipid, glucose and protein metabolism in obesity-associated diseases, including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) and their cardiovascular complications. We use different systems biology approaches coupled with biochemical and molecular techniques to elucidate the mechanisms of disrupted glucose, lipid and protein homeostasis, in the hope of uncovering novel therapeutic approaches.
Yoon-Kwang Lee, Ph.D.
Dr. Lee’s laboratory investigates the underlying molecular mechanisms of obesity and how they are related to metabolic disorders such as diabetes and fatty liver disease, which are pandemic in modern society due to high caloric intake and sedentary lifestyle. They focus on the group of proteins playing critical roles in bile acid and lipid synthesis pathways. Dr. Lee uses mouse models deficient in each of these proteins, which are strongly reminiscent of these disorders. The molecular and biochemical assessment of these models will help to understand the development of metabolic disorders and provide therapeutic or preventative approaches to halt their progression.
Priya Raman, Ph.D.
Dr. Raman’s laboratory studies vascular complications associated with diabetes, obesity and metabolic syndrome (MetS). In particular, our laboratory is interested in the role of ‘non-lipid factors’ such as thrombospondin-1 (TSP-1, a matricellular protein) and O-linked N-acetylglucosamine signaling (O-GlcNAc, a post-translational protein modification) in the pathogenesis of macrovascular disorders associated with diabetes and metabolic syndrome. We are specifically interrogating the cellular and molecular mechanisms by which TSP-1 and O-GlcNAc signaling regulate transition of VSMC and macrophages to atherogenic and inflammatory phenotypes, triggering augmented atherosclerotic complications in diabetes and MetS. We utilize a variety of biochemical, histological and molecular biology approaches in combination with en-face atherosclerotic lesion assay, non-invasive high-frequency ultrasound imaging, EchoMRI and CLAMS studies. In addition, we use human and mouse cell culture models in conjunction with in vivo mouse models of diabetes, obesity and atherosclerosis, including both conventional and inducible tissue-specific knockout mice.
Liya Yin, M.D., Ph.D.
Dr. Yin’s lab works on lipid metabolism, atherosclerosis, and cardiovascular phenotypes in metabolic syndrome, such as dysregulation of coronary circulation, impaired coronary collateral growth, stem cell dysfunction in cardiovascular regeneration. Her group performs a variety of in vitro and in vivo studies to investigate the pathogenic mechanisms of cardiovascular diseases, in hoping for identifying novel therapeutic approaches.