Insulin resistance is a major factor responsible for the pathogenesis of type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD)/ nonalcoholic steatohepatitis (NASH), obesity associated cancers and neurodegenerative disease. Over the last three decades my laboratory has pioneered the development and application of nuclear magnetic resonance spectroscopy combined with stable isotopes and GC-MS, LC-MS/MS analyses to assess tissue specific flux rates of glucose and fat metabolism in vivo in both humans and awake transgenic rodent models of insulin resistance in order to elucidate the molecular basis of insulin resistance. These studies have in turn provided paradigm-shifting insights into the cellular and molecular mechanisms of lipid-induced insulin resistance in liver and skeletal muscle which my group has established in both humans and rodent models of NAFLD and type 2 diabetes. Based on these studies, my group has now developed novel liver-targeted mitochondrial protonophores that reverse hyperlipidemia, insulin resistance, diabetes, NAFLD, NASH and liver fibrosis in rodent models of type 2 diabetes and NASH, which are now in clinical development. During my tenure at Yale, I have had the pleasure of mentoring well over 100 trainees, and more than three dozen of these trainees have gone on to direct their own research laboratories around the world.
Non-Alcoholic SteatoHepatitis (NASH); liver targeted mitchondrial uncoupling for treatment of NAFLD/NASH
Endocrine System Diseases; Insulin Resistance; Molecular Biology; Physiology; Non-alcoholic Fatty Liver Disease; Chemicals and Drugs; Analytical, Diagnostic and Therapeutic Techniques and Equipment
Cardiovascular Diseases; Metabolism; Nutrition; Obesity