Diabetes and non-alcoholic fatty liver disease (NAFLD) are closely associated with hepatic fat and cholesterol accumulation, hepatocyte organelle dysfunction, low grade inflammation, and dyslipidemia. Patients with diabetes and NAFLD have significantly higher risk of cardiovascular disease, which remains the leading cause of death worldwide. Bile acids are synthesized from cholesterol only in the liver. Hepatic bile acid synthesis is the only major cholesterol catabolic elimination mechanism in the body, and bile acids act as physiological detergents to facilitate dietary lipid and fat-soluble vitamin absorption in the small intestine. Furthermore, bile acids are signaling molecules that critically regulate metabolic homeostasis and inflammatory response by activating nuclear receptors and intracellular signaling pathways. Different therapeutic approaches targeting the bile acid signaling pathways have shown great promise for treating metabolic and chronic liver diseases including cholestasis, dyslipidemia, diabetes, and fatty liver disease. The major focus of the lab is to investigate how modulating the enterohepatic bile acid signaling impacts the complex metabolic network that controls lipid, glucose, and amino acid metabolism, insulin sensitivity, and inflammation. Through these studies, we hope to better understand disease pathophysiology and help establish the molecular basis for developing effective therapies. We address these questions by employing experimental mouse models through viral vector-mediated liver-specific gene delivery, tissue-specific genetic knockout, and pharmacological treatment approaches and a combination of physiological, molecular cell biology techniques and unbiased transcriptomics and metabolomics approaches.