The goal of the Alcohol Center of Research-Nebraska (ACORN) is to expand existing strengths and expertise in Nebraska to develop a novel niche in alcohol research, by creating a Center focused on the Alcohol Exposome. Alcohol research has been a major area of emphasis in Nebraska (at the Omaha VA Medical Center Research Service and at the University of Nebraska Medical Center) for over 5 decades. As a result, many contributions to the field of alcohol research and the treatment of alcoholic liver disease have been made. Studies examining the effects of alcohol on trace metal metabolism, lung biology and physiology, mechanisms of alcoholic fatty liver, role of aldehyde adducts in alcoholic cell injury, hepatic protein trafficking and signal transduction events and the role of immune mechanisms in alcoholic liver disease have been some of the key areas of investigation. Our goal is to translate to humans how factors in the exposome such as age, nutritional status, cigarette smoking, and exposure to pathogens interact in the presence or absence of alcohol administration. We know that a major component of the specific external environment is the lifestyle factor of alcohol consumption. Thus, under the comprehensive schema of the exposome, alcohol represents an environmental exposure that should be considered in context with other internal and external factors to understand causes and nature of disease progression. The overall hypothesis of our application is the following: the examination of alcohol in the context of the exposome will allow us to understand its role more fully in the etiology of disease and the subsequent manifestations of alcohol-induced human pathophysiology. The alcohol-exposome theme of the center is unique among alcohol centers and has the potential to be highly translational. Our investigators represent an outstanding team of interdisciplinary investigators that will be supported by an Administrative Core, a Biospecimen Core, and a Pilot Projects Core. ACORN investigators will have access to state-of-the art facilities at UNMC, Nebraska Medical Center and University of Nebraska-Lincoln. We include faculty from 5 departments and 3 colleges. Our proposed Specific Aims for the ACORN are to: 1) Facilitate interdisciplinary research and identify factors so that we can translate in humans how age, nutritional status, cigarette smoking, and exposure to pathogens interact in the presence or absence of alcohol administration. 2) Create a Biospecimen Core to aid Center investigators in promotion and development of translational animal and human tissue and cell models. 3) Enhance the collaborative ACORN environment and provide opportunities for funding through training, symposia, and pilot grants. Work on our 4 research projects, with participation of the Administration Core and the Biospecimen Core will allow us to realize our goals. Overall, this new P50 will utilize the expertise and knowledge of past research efforts to examine how al...