The overall goal of the Northern Ohio Alcohol Center (NOAC) is to identify specific molecular targets of ethanol-induced damage, as well as understand the complex adaptive and maladaptive responses of cells and systems to that injury. This information will enable us to 1) target therapeutic interventions that will either slow and/or reverse the progression of alcohol-induced tissue injury and 2) develop specific assays that can assess the efficacy of novel therapeutic strategies in relevant clinical populations. NOAC brings together an outstanding team of interdisciplinary investigators including geneticists, cell biologists, oxidation biochemists, biomarker experts, synthetic chemists and clinical translational investigators. Progress by these investigators into the mechanisms of ethanol-induced tissue injury is supported by the Animal Models and Cell Isolation Core. The use of standardized protocols for in vivo models of acute and chronic ethanol exposure to rodents, as well as the use of in vitro primary cell cultures isolated from ethanol-exposed animals, is critical to understanding the molecular mechanisms for the pathogenesis of alcohol-induced tissue injury. The purpose of the Animal Model and Cell Isolation Core is to provide centralized facilities for the exposure of rats and mice to ethanol in support of Research Components and Pilot Projects supported by NOAC, as well as additional projects funded by NIAAA and other sources. We also provide access to our animal/cell models and biorepository as a national and international resource. This Core also uses standardized protocols for the isolation of hepatocytes and non-parenchymal cells from the liver, providing these cells in support of both NOAC and other alcohol and non-alcohol related research projects. Personnel experienced in working with rat and murine models of acute and chronic ethanol exposure, as well as isolating parenchymal and non- parenchymal cells from rodents, staff the Animal Models and Cell Isolation Core. The proposed Research Components and Pilot Projects will make use of the Animal Models and Cell Isolation Core. The major goal of the Animal Models and Cell Isolation Core will be to make available to members of NOAC tissue and cellular samples from control and ethanol-exposed animals. The procedures involved are complex and expensive; the availability of centralized facilities will allow rapid access of investigators in NOAC, as well as investigators new to alcohol research, to the tissues and cells needed to test novel and innovative hypotheses without the delay of each PI developing these techniques in each of their own laboratories. The Animal Core also maintains an extensive biorepository of tissues and cells from ethanol-exposed mice and rats; this biorepository will allow for considerable cost savings that result from the shared use of samples between the different members of NOAC. The combination of our outstanding investigative team ...