# Center for Alcohol Research in Epigenetics

> **NIH NIH P50** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $1,654,973

## Abstract

Project Summary:
Alcohol use disorder (AUD) can be characterized by a pattern of compulsive alcohol drinking or loss of control
over alcohol drinking. The positive and negative effects of ethanol appear to be regulated by genetic and
epigenetic changes in several key brain regions. Long-term alcohol use causes structural and functional
changes in the prefrontal cortex (PFC), hippocampus, amygdala, and ventral tegmental area of the brain which
may drive behavioral phenotypes, such as anxiety, depression, motivation, and increased alcohol drinking.
Several protein families such as histone deacetylases (HDACs), histone acetyltransferases (HATs), histone
methyltransferases (HMTs), DNA methyltransferases (DNMTs), lysine demethylases, and DNA demethylases
are important players in chromatin remodeling within the genome and are altered by chronic ethanol exposure
and withdrawal. However, the interplay between these different epigenetic modifiers lead to an altered state of
the epigenome and their role in transcriptomic changes associated with adaptations in the reward and stress
systems in the brain (VTA, amygdala, PFC, and hippocampus) during AUD is still unclear. The overall aim of
this Alcohol Research Center is to evaluate the epigenetic and genetic basis of molecular changes in
the brain that underlie behavioral changes in AUD. This P50 application entitled “Center for Alcohol
Research in Epigenetics (CARE)” consists of four highly inter-related preclinical and translational research
projects [research project #1, VTA, (Brodie /Glover), research project #2, Amygdala, (Pandey), research project
#3, Hippocampus, (Lasek) and research project #4, PFC, (Guidotti/Grayson/Gavin)] and two current pilot
projects [pilot project #1 (Epigenetic biomarkers in AUD), and pilot project #2 (Epitranscriptomic modifications in
AUD)], and three Cores [Administrative (Pandey/Lasek), Epigenetics (Grayson/Maienschein-Cline), and
Behavioral Core (Glover/Zhang)]. In addition, the CARE will serve as an important resource and provide a
scientifically enriched environment for training opportunities for the next generation of neuroscientists studying
AUD and will disseminate scientific knowledge of AUD to the general public through a community outreach
program. The primary thematic focus of CARE, as a whole, will be to mechanistically link emerging novel
molecular targets identified by whole-genome approaches (ATAC-seq, ChIP-seq, RNA-seq, and DNA
methylation/demethylation EPIC array) in the proposed brain circuitry to behavioral phenotypes. Mechanistic
approaches (CRISPR-dCas9, shRNA, siRNA, chemogenetic) will be used to manipulate the epigenome
through alterations of either histone acetylation/methylation mechanisms or DNA methylation mechanisms, in
key brain circuitry that regulates behavioral phenotypes associated with AUD (anxiety, depression, motivation,
and alcohol drinking) in order to better understand the pathophysiology of AUD and develop better
pharmacotherapy.

## Key facts

- **NIH application ID:** 10380644
- **Project number:** 5P50AA022538-08
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** SUBHASH C. PANDEY
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,654,973
- **Award type:** 5
- **Project period:** 2015-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380644

## Citation

> US National Institutes of Health, RePORTER application 10380644, Center for Alcohol Research in Epigenetics (5P50AA022538-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380644. Licensed CC0.

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