# 3/11 Epigenetic Regulation of Neuroimmune Pathways

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $601,471

## Abstract

PROJECT SUMMARY
Alcohol use disorder (AUD) is a debilitating neuropsychiatric disorder, negatively affecting the lives of millions
of individuals worldwide. Chronic ethanol exposure is known to alter multiple molecular pathways throughout
the central nervous system, including aberrant neuroimmune signaling. As part of the Integrative Neuroscience
Initiative on Alcoholism (INIA) Neuroimmune consortium, the proposed collaborative research project will focus
on the contribution of long non-coding RNAs (lncRNAs) to molecular adaptations in the neuroimmune system
and development of AUD. The non-coding transcriptome significantly outnumbers the protein-coding
transcripts, but the biological function of most non-coding RNAs has yet to be determined. Several studies
have suggested that lncRNAs are critical epigenetic regulators of genomic structure and long-term gene
expression. We hypothesis that lncRNAs are epigenetic modulators of gene expression in response to ethanol
that actively coordinate persistent alterations in cellular function and animal behavior. We have proposed three
specific aims to experimentally test this hypothesis and help accomplish the overall goals of the INIA
consortium. Aim 1 will use Perturb-Seq to functionally test the involved of lncRNAs in neuroimmune gene
expressing using an established in vitro model of ethanol exposure. Combining use of the clustered regularly
interspaced short palindromic repeats (CRISPR) genome editing approach with high-throughput RNA-
Sequencing this aim will identify neuroimmune pathways regulated by specific lncRNAs. Aim 2 will use
chromosome conformation capture sequencing to demonstrate physical changes in the spatial orientation of
chromatin (e.g., promoter-enhancer interactions) due to excessive ethanol exposure. This specific aim will
create a new genome-wide chromatin interaction map that will identify regulatory elements involved in the
ethanol-responsive neuroimmune pathways. Aim 3 will use CRISPR-mediated genome editing in vivo
strategies to determine the role of individual lncRNAs in regulating neuroimmune activation and ethanol-related
behavioral phenotypes. This specific aim will create several novel genetically engineered lines of mice, for
multiple collaborative projects, to test ethanol-related behaviors and molecular mechanisms associated with
excessive ethanol exposure. Completion of the proposed research will broaden our understanding for
epigenetic regulation of the neuroimmune system in AUD and determine molecular adaptations underlying
excessive ethanol exposure.

## Key facts

- **NIH application ID:** 10410092
- **Project number:** 2U01AA020889-11
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sean P Farris
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $601,471
- **Award type:** 2
- **Project period:** 2011-09-05 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410092

## Citation

> US National Institutes of Health, RePORTER application 10410092, 3/11 Epigenetic Regulation of Neuroimmune Pathways (2U01AA020889-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10410092. Licensed CC0.

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