The Epigenetics Core gives scientific support to investigate the impact of chronic ethanol exposure on gene expression and epigenetic regulation in specific brain regions of animal model of AUD as well as in human postmortem brain of AUD subjects. Building on previous bulk tissue analyses, the project now employs advanced techniques, including single-nuclei RNA sequencing and ATAC sequencing, to explore gene expression and chromatin accessibility in various cell types. Additionally, the project includes spatial transcriptomics to validate gene localization, epigenetic editing to modify gene expression, and scanning electron microscopy for examining synaptic characteristics. Collectively, these efforts will provide a detailed understanding of the molecular and cellular changes that result from withdrawal following chronic ethanol consumption.

Focused on the ventral tegmental area (VTA), a key region involved in reward and motivation, this project explores how alcohol withdrawal reshapes gene expression, neuronal activity, and behavior, with the goal of understanding how physiological changes in the VTA during alcohol withdrawal promote relapse. Researchers are investigating the epigenetic regulation of alterations in neuroimmune signaling and GABA sensitivity during withdrawal that contribute to alcohol craving and relapse. Using advanced tools such as single-nucleus RNA and ATAC sequencing, spatial transcriptomics, 3D electron microscopy, and CRISPR-based epigenetic editing, the team aims to pinpoint cell-specific molecular changes in the VTA. These integrated studies will uncover the epigenetic mechanisms underlying alcohol withdrawal and guide the development of new therapeutic strategies for alcohol use disorder.

This project investigates how alcohol withdrawal triggers anxiety-related behaviors by altering gene expression and epigenetic regulation in the amygdala, a brain region central to fear and anxiety. Proposed research will aim to uncover how changes in chromatin accessibility and histone modifications affect neuronal structure and activity in the central amygdala, as well as related behavior phenotypes in animal model of AUD during ethanol withdrawal. Using advanced methods such as single-nucleus RNA and ATAC sequencing, spatial transcriptomics, CRISPR-based epigenetic editing, and 3D electron microscopy, the study will identify and test key genes driving withdrawal-induced anxiety. Translation research will be performed in the postmortem amygdala of AUD subjects. Ultimately, this work seeks to reveal epigenetic targets that could inform new treatments for alcohol use disorder (AUD).

This project examines how alcohol withdrawal alters epigenetic and transcriptomic regulation in specific cell types within the hippocampus, a brain region critical for emotion and memory. Building on findings that withdrawal produces epigenetic modifications and changes in neuroimmune gene expression, researchers aim to uncover how these molecular changes at single-cell level contribute to depression-, anxiety-, and PTSD-like behaviors linked to alcohol use disorder (AUD). Using techniques such as chromatin immunoprecipitation, single-cell 10x genomics, and CRISPR-based epigenetic editing, the study will identify and manipulate genes that drive these maladaptive effects of ethanol withdrawal. Overall, this work seeks to define the epigenetic mechanisms connecting ethanol withdrawal to emotional dysfunction, providing insight for developing targeted treatments for AUD and its comorbidities.

This project investigates how alcohol withdrawal alters the medial prefrontal cortex (mPFC) to promote cognitive deficits and heightened pain sensitivity during early abstinence. Researchers focus on epigenetic and transcriptional changes in the mPFC that alter neuroimmune signaling and synaptic plasticity, using both human postmortem tissue and rodent models. Advanced techniques, including single-cell analysis and CRISPR-dCas9 gene editing, will be used to identify cell-type-specific changes and test whether reversing these modifications can restore normal brain function and behavior. The study aims to reveal mechanistic targets for developing treatments for cognitive and nociceptive symptoms of withdrawal and improve recovery in individuals with alcohol use disorder.