Dr. Zang is a Professor of Molecular Medicine and the Ewing Halsell Distinguished Chair in aging research at the Barshop Aging Institute, the University of Texas Health San Antonio (UTHSA). Dr. Zang’s research is centered on deciphering the cellular and molecular mechanisms governing the role of nutrient sensing and its regulators in controlling metabolic homeostasis. Her work focuses on understanding how these processes are disrupted in metabolic liver diseases related to aging, such as diabetes, non-alcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD). The long-term goal of her work is to translate these findings into potential therapies for humans. Since Zang’s laboratory discovered hepatic lipogenesis as a critical contributor to the pathogenesis of NAFLD and ALD, her laboratory focuses on understanding how hepatic metabolic homeostasis is controlled by nutrient sensing network. Using a variety of approaches, including genetically engineered mice, biochemical, pharmacologic, and metabolomic/lipidomic approaches, her laboratory has identified several novel specific pathways that control metabolic homeostasis and elucidated how these processes are dysregulated in disease progression. Most recently, her lab indicates that age-dependent defects in nutrient sensing impair the capacity to resolve liver fibrosis during aging. Studies from her laboratory have made pioneering discoveries regarding master nutrient sensors, such as FGF21, SIRT1, and AMPK, and resulted in a number of original manuscripts in top-ranked journals, such as Aging Cell, Cell Metabolism, Hepatology, Gastroenterology, and Diabetes. These studies are being used as a platform for developing new therapeutics. For instance, FGF21 is currently undergoing Phase II clinical trials for the treatment of diabetes. Currently, her laboratory focuses on three highly integrated areas: 1) Identify and characterize the role and molecular mechanisms of novel nutrient sensing in metabolic control; 2) Elucidate how aberrant changes in novel nutrient-sensing pathways contribute to the pathogenesis of diabetes and metabolic liver diseases; and 3) Exploring the mechanistic role of nutrient sensing in the basic biology of aging and age-related diseases. 

Representative Citations:

Adjei-Mosi J, Sun Q, Smithson SB, Shealy GL, Amerineni KD, Liang Z, Chen H, Wang M, Ping Q, Han J, Morita M, Kamat A, Musi N, Zang M. Age-dependent loss of hepatic SIRT1 enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution. Aging Cell. 2023 Mar 31;e13811.doi: 10.1111/acel.13811. PMID: 36999514.

Chen H, Shen F, Sherban A, Nocon A, Li Y, Wang H, Rui X, Han J, Jiang B, Li N, Keyhani-Nejad F, Fan J, Liu F, Kamat A, Musi N, Pacher P, Gao B, Zang M. DEP-domain containing mTOR-interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease. Hepatology. 2018; 68: 496-514.  PMCID: PMC6097912.  

Li Y, Wong K, Giles A, Lee JW, Jiang J, Adams AC, Kharitonenkov A, Yang Q, Gao B, Guarente L, Zang M. Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21. Gastroenterology. 2014; 146: 539–549. PMCID: PMC4228483

Li Y, Xu S, Mihaylova M, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin resistant mice. Cell Metabolism. 2011; 13: 376-388. PMCID: PMC3086578. Selected as the most cited article in Cell Metabolism