Center for Circadian Rhythms and Alcohol-Induced Tissue Damage

ABSTRACT Fundamental unanswered questions in the field of alcohol research include: why do only a subset of individuals with an alcohol-use disorder develop clinically significant organ damage and what factors predispose subjects with AUD to develop organ failure in a specific organ? Studies provide compelling evidence to support the

hypothesis that disruption of circadian homeostasis is a plausible susceptibility factor for host and organ-specific vulnerability to alcohol-induced pathologies. Interest in the study of circadian rhythms is growing; however, an obstacle to study the interactions between circadian rhythms and alcohol-induced organ damage has been the

lack of a combined circadian rhythm and alcohol expertise (and the underlying molecular mechanisms) and the high cost associated with establishing the infrastructure necessary to assess and manipulate circadian rhythms. The objective of this R24 Alcohol Research Resource Program “Center for Circadian Rhythms and Alcohol-

Induced Tissue Damage” is to fill these unmet needs. The objective of Phase I (current funding period) of this Center focused on advancing awareness of the topic and availability of Center resources, providing resources and support to investigators, as well as training and mentoring of junior investigators. With NIAAA-support we

provided services to nearly 60 investigators resulting in 23 publications, provided support for 28 grant applications (5 funded), and training / mentoring of 13 junior investigators. The objective of this competitive renewal (Phase II) is to build on Phase I success by continuing to provide the infrastructure, support, and

expertise to enable to conduct research on the topic of alcohol and circadian rhythms. Additionally, in response to requests from users we will provide additional resources for mechanistic evaluations to evaluate the relationship between alcohol and circadian rhythms including microbiota, intestinal barrier, and intestinal-derived

inflammation. These objectives will be attained by pursuing the following Aims. Aim 1. Promote awareness of the topic and the opportunity to incorporate circadian rhythms, microbiota, and gut-derived inflammation into mechanistic, therapeutic, and translational alcohol research studies. Contribution to the Community: Increased

awareness of circadian rhythms in alcohol research (and mechanisms) and venues to support dialogue and collaborations to be a springboard for innovative research. Aim 2. Provide the essential resources to incorporate circadian rhythms in alcohol research for human and animal studies as well as mechanistic evaluations of

microbiota and gut-derived inflammation. Contribution to the Community: Give researchers the skills and resources to test innovative hypotheses. In summary, continuation of this R24 Center will engage and provide researchers with the skills, resources, and assistance to explore innovative hypotheses, and bring new

investigators into the field of alcohol research including junior faculty and trainees. These efforts are expected to lead to the identification of novel targets and interventions to prevent and treat alcohol-induced organ damage now and in the years to come.