My research work focuses on translational aspects of type 2 diabetes and other aging-related metabolic diseases, from identification and validation of novel drug targets, development of high throughput screening assays, to preclinical testing of potential therapeutic compounds in animal models. Our work has recently identified a critical missing link between mitochondrial dysfunction in aging and the onset aging-related metabolic diseases, including diabetes, obesity, cardiovascular diseases. We are also uncovering novel signaling pathways that regulates glucose-sensing by pancreatic beta cells, since a loss of glucose responsiveness by pancreatic beta cell is a major pathological event that triggers the onset of type 2 diabetes.
Wang L, Liu X, Nie J, Zhang J, Kimball SR, Zhang H, Zhang WJ, Jefferson LS, Cheng Z, Ji Q, Shi Y.ALCAT1 controls mitochondrial etiology of fatty liver diseases, linking defective mitophagy to steatosis. Hepatology. 2015 Feb;61(2):486-96.
Nie J, Liu X, Lilley BN, Zhang H, Pan YA, Kimball SR, Zhang J, Zhang W, Wang L, Jefferson LS, Sanes JR, Han X, Shi Y. SAD-A kinase controls islet β-cell size and function as a mediator of mTORC1 signaling. Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13857-62.
Nie J, Lilley BN, Pan YA, Faruque O, Liu X, Zhang W, Sanes JR, Han X, Shi Y. SAD-A potentiates glucose-stimulated insulin secretion as a mediator of glucagon-like peptide 1 response in pancreatic β cells. Mol Cell Biol. 2013 Jul;33(13):2527-34.
Li J, Liu X, Wang H, Zhang W, Chan DC, Shi Y. Lysocardiolipin acyltransferase 1 (ALCAT1) controls mitochondrial DNA fidelity and biogenesis through modulation of MFN2 expression. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6975-80.
Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y. Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab. 2010 Aug 4;12(2):154-65.
Complete List of Published Work in MyBibliography: