# 1/1 NADIA U24 Epigenetic/Molecular Scientific Resource Core

> **NIH NIH U24** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $503,685

## Abstract

ABSTRACT
Alcohol is one of the most widely used addictive drugs in adolescence, and continued use can lead to the
development of psychiatric disorders, including alcoholism, in adulthood. Epigenetic processes, such as
histone acetylation and DNA methylation mechanisms, have been shown to play a role in neuromaturation by
contributing to the stability of gene expression during brain development. The Neurobiology of Adolescent
Drinking in Adulthood (NADIA) consortium has revealed that adolescent intermittent ethanol (AIE) exposure
produces epigenetic reprogramming in several brain circuits (prefrontal cortex, basal forebrain, hippocampus
and amygdala) that persists until adulthood and might be responsible for adult psychopathology. These
findings prompt determination of the global epigenome to determine AIE altered specific gene loci within key
brain regions. The Epigenetic/Molecular Core is developed to evaluate epigenetic mechanisms in specific brain
regions linked to key AIE phenotypes in adulthood. The Epigenetic/Molecular Core will also develop tools for
CRISPR/dCas9 approaches for epigenetic editing of target genes to directly link AIE-induced behavioral
phenotypes with molecular mechanisms. The objectives of the Core are to provide tools and scientific
expertise to test NADIA’s hypotheses that perturbations of epigenetic targets due to AIE may lead to
dynamic changes in epigenetic programming leading to transcriptomic changes in key brain areas
(prefrontal cortex, amygdala, hippocampus, hypothalamus, and basal forebrain) which are responsible
for persistent behavioral and molecular phenotypes in adulthood. These objectives will be achieved with
the following proposed work: 1) To examine the status of the epigenome at the whole genome level. We will
perform Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) to determine the locations of
open and closed chromatin domains in different brain regions studied across NADIA. The core will provide
information on global chromatin states during AIE to each component and identify “hub” genes related to the
component’s hypotheses for functional studies. 2) To determine gene specific AIE-induced epigenetic
modifications (histone acetylation/methylation/DNA methylation) associated with changes in gene expression.
3) To provide gene specific CRISPR/dCas9 tools for NADIA components. The core will develop and test
CRISPR/dCas9 technologies to make epigenetic editing (activating or silencing) at specific gene locations and
evaluate both functional and behavioral consequences. These studies will provide a better understanding
of AIE-mediated changes in gene expression via epigenetic reprogramming across NADIA
components. In addition, we will be able to identify mechanisms that may lead to the development of
novel treatment strategies for adult psychopathologies resulting from adolescent binge drinking.

## Key facts

- **NIH application ID:** 10074081
- **Project number:** 2U24AA024605-06
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** SUBHASH C. PANDEY
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $503,685
- **Award type:** 2
- **Project period:** 2015-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074081

## Citation

> US National Institutes of Health, RePORTER application 10074081, 1/1 NADIA U24 Epigenetic/Molecular Scientific Resource Core (2U24AA024605-06). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074081. Licensed CC0.

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