The University of Louisville Alcohol Research Center (ULARC) was created to serve as a regional/national resource to perform interdisciplinary collaborative research on the role of nutrition as a cofactor in alcohol induced organ injury and as a possible therapeutic intervention to prevent/treat this organ injury. The nutrition and alcohol-induced organ injury theme of the center is unique among alcohol centers. The approach is highly translational. Our investigators include faculty from 13 departments and 6 colleges. The Specific Aims of the ULARC are to: 1) perform/facilitate interdisciplinary research on nutrition and alcohol-induced organ injury; 2) serve as a regional/national resource for the study of nutrition and alcohol-induced organ injury; 3) develop potential therapeutic targets/interventions for alcohol induced organ injury based on the mechanistic research of the ULARC; and 4) disseminate knowledge/interventions to the scientific and lay communities. We will explore interactions of nutrition and alcohol abuse in the development of alcohol-induced organ dysfunction, and we will evaluate diverse potential nutritional preventive/therapeutic interventions. Project 1 (Kirpich/McClain) evaluates the role of dietary fat in ALD pathogenesis; Project 2 (Barve) evaluates alcohol- induced epigenetic alterations in the gut:liver axis. Project 3 (Chen) will elucidate the mechanisms by which enhancers mediate ethanol-induced developmental impairment of neural crest cells and teratogenesis and unique exosome treatment for prevention of FASD. Project 4 (Feng) studies the beneficial effects of the probiotic, Lactobacillus rhamnosis GG (LGG)on the gut:liver axis in ALD. Together, these projects form a cohesive and interactive approach to investigate the effects of nutrition and nutritional interventions on alcohol-induced organ injury.