Richard Green, MD
Professor, Medicine
Research Program
Cancer-Focused Research
The goal of Dr. Green's research is to understand the role of the unfolded protein response (UPR) in hepatic bile acid and lipid metabolism, and the effects on hepatocellular injury and the development of liver cancer. Non-alcoholic steatohepatitis and cholestatic liver diseases such as Primary Sclerosing Cholangitis can cause liver cancer, even in the absence of cirrhosis. Current interests in the laboratory focus on the interaction of the hepatic IRE1alpha/XBP1 pathway of the UPR and bile acid signaling via the nuclear receptor FXR and FGF19. We have demonstrated that FXR regulates IRE1alpha/XBP1 activity, and that IRE1alpha/XBP1 signaling reciprocally regulates bile acid metabolism. We have recently developed mice lacking both hepatic FXR and select UPR signaling which develop spontaneous liver cancer. In addition, we utilize other murine models of hepatocellular carcinoma such as MDR2-knockout mice to further investigate the role of the UPR on liver disease progression and carcinogenesis. The long term goals of these investigations are to better understand the role of bile acid and other lipid signaling in the progression of liver disease and cancer; and to identify UPR proteins and genes that can be targeted to treat progressive liver disease and hepatocellular carcinoma.