Hepatocyte FOXA3 in Alcohol-Associated Liver Disease

Project Summary Project Summary: Alcohol-associated liver disease (ALD) is the most prevalent type of chronic liver disease worldwide. ALD represents a spectrum of liver disorders resulting from alcohol use, ranging from alcohol- associated hepatic steatosis (i.e., alcoholic fatty liver) to more advanced forms, including alcohol-associated steatohepatitis (ASH)/hepatitis (AH) and cirrhosis (AC). Alcohol-associated hepatic steatosis is the result of the earliest response of the liver to alcohol abuse. So far, the mechanism underlying the pathogenesis of ALD remains to be fully understood. There are also limited options for the treatment of ALD. Our preliminary study shows that hepatic forkhead box A3 (FOXA3), a member of the winged-helix transcription factors, is reduced in patients or mice with ALD. In this project, we will investigate the role of hepatic FOXA3 in the development and progression of ALD. We will also characterize the underlying mechanisms. Gain- and loss-of-function approaches and state-of-the-art techniques will be used to investigate whether hepatic FOXA3 is a key player in the pathogenesis of ALD.