Liver diseases including alcohol- and drug-induced liver injury, fatty liver disease, viral hepatitis, and liver cancer affects millions of people in he US. For the past 9 years the COBRE supported the recruitment of 15 junior faculty engaged in liver research and assisted in the development of highly successful core laboratories at the University of Kansas Medical Center. These COBRE-supported faculty and core users published more than 500 publications and generated more than $38 million of grant funding including 24 R01 grants. In addition, this led to the establishment of a Liver Center at KUMC and a liver tissue bank. Overall, the COBRE Phase I and II were instrumental in establishing a flourishing liver research community and creating an important infrastructure to support liver research and other areas of biomedical research at KUMC and beyond. This application requests five years of funding for the Phase III of this COBRE, during which we will pursue the following specific aims: 1. To provide administrative support for the successful operation of the COBRE; 2.To improve and sustain two scientific cores, the human Liver Cell Isolation Core and the Analytical Core, so that they can enhance the research capabilities of faculty at KUMC and at KU; 3. To operate a pilot grants program to provide incentives for pursuing new liver research opportunities and collaboration. The result will be a very strong and highly motivated group of senior and mid-career liver research scientists at KUMC who form the basis for NIH-funded Liver Center and/or program project grant applications. In addition, KUMC assists several vital, self-sustaining core laboratories that support liver and other biomedical research. Thus, the overall impact of this COBRE at KUMC will substantial and long-lasting. The liver has many vital functions in the body including roles in fat, glucose and amino acid metabolism, synthesis of serum albumin, clotting and complement factors, synthesis and secretion of bile acids, and modification and elimination of drugs and chemicals. Disturbances of these functions cause liver disease manifested as cell injury, steatohepatitis, fibrosis, cirrhosis and liver cancer affecting millions of people in the US. This proposal provides support for pilot projects and core research and administrative facilities to perform basic and translational studies of mechanisms of liver diseases.