Administrative Core

Project Summary: The Administrative Core of this renewal P50 application on “Center for Alcohol Research in Epigenetics (CARE)” will coordinate with multiple research projects and the Epigenetics Core that is comprised of multidisciplinary research teams. The goal of CARE is to evaluate ethanol withdrawal-induced transcriptomic and epigenomic changes at the single-cell level in key brain regions, and then causally link these changes to structural and functional changes leading to development of behavioral phenotypes such as anxiety, depression, panic, pain, cognition deficits and reduced reward sensitivity during withdrawal after chronic ethanol exposure. To achieve the above goal, we have selected four interrelated research projects and one resource core i.e., Epigenetics Core, and will be utilizing a rat model of alcohol dependence and human postmortem brain tissue to discover integrated and functional facets of the transcriptome and epigenome at the single cell level in AUD. Our approach is based on the idea that epigenomic and transcriptomic changes in early withdrawal after chronic ethanol exposure contributes to the maintenance of AUD. Research projects #1, #2, #3 and #4 will evaluate cellular heterogeneity of transcriptomic and open chromatin accessibility in the ventral tegmental area (VTA), central nucleus of amygdala (CeA), dorsal hippocampus, and medial prefrontal cortex (mPFC) using 10x Genomics (snRNA-seq and snATAC-seq). We will link these changes to structural and electrophysiological responses and several behavioral phenotypes using cell type-specific CRISPR/dCas9 tools and other gene manipulation approaches. We have incorporated several pharmacological agents to modulate molecular changes in specific brain regions and examine the changes in withdrawal symptoms in several CARE projects. The Administrative Core will provide administrative leadership, overall management, and oversight in order to enhance our understanding of the genomic and epigenomic basis of AUD. This Core will also manage community outreach and training programs within CARE as well as the data management and sharing plan. The Administrative core of CARE will also be responsible for maintaining robust educational activities related to AUD for trainees and faculty engaged in research. Overall, the Administrative Core will maintain a productive and interactive environment to enhance epigenetic, molecular, and behavioral research in AUD. This multidisciplinary endeavor will help us identify novel therapeutic molecular and epigenetic targets to prevent and treat AUD.