Dr. Ke’s primary research interest is focused on understanding the fundamental mechanisms underlying liver ischemia and reperfusion injury (IRI), a major cause of hepatic dysfunction and failure following liver transplantation, resection, and hemorrhagic shock. It is recognized that IRI activates liver macrophages (Kupffer Cells) to generate reactive oxygen species (ROS), leading to inflammatory injury in the liver. Recent studies revealed that activation of the NLRP3 inflammasome required ROS-dependent NEK7, a serine-threonine kinase involved in mitotic cell division. NEK7 directly binds to NLRP3 and promotes inflammatory response. The overall goal of Dr. Ke is to dissect the functions and molecular mechanisms by which Heat-shock factor 1 (HSF1) regulates NEK7 function in liver IRI. In addition to this ongoing project supported by the National Institutes of Health (NIH), Dr. Ke has extended his research to investigate the mechanistic roles of lipid metabolism and innate immune response in nonalcoholic steatohepatitis (NASH). Emerging evidence has indicated lipid-induced oxidative stress involving activation of endoplasmic reticulum (ER)-resident adaptor protein stimulator of IFN genes (STING), a central player in initiating innate immune and proinflammatory signaling. Increased STING expression was observed in Kupffer cells in patients with NASH and a mouse model of high-fat diet-induced steatosis. The overarching goal of this study is to elucidate the molecular mechanisms of immune-metabolic interactions in NASH progression. Recent publications from Dr. Ke’s lab highlight the key role of STING as a regulator of lipid metabolism. Dr. Ke has served as a principal investigator in several NIH grants and has received many investigator awards from the American Society of Transplantation, the American Society of Transplant Surgeons, and The Transplantation Society. He is currently an editorial board member of Hepatology and an associate editor of Frontiers in Transplantation