# lncRNA Gas5 dysregulation alters ethanol drinking behavior and ethanol-related phenotypes

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $46,752

## Abstract

Project Summary
Alcohol use disorder (AUD) is a chronic, debilitating, and relapsing brain disease. An overwhelming number of
people die yearly due to alcohol-related causes; however, the mechanism(s) of action are challenging to decipher
and remain largely elusive.
Long noncoding RNAs (lncRNAs) are key regulators of the genome; persistent transcriptional changes induced
by chronic ethanol exposure is a hypothesized mechanism for AUD development, withdrawal, and relapse. Our
laboratory and others have shown that ethanol-responsive lncRNAs have the ability to directly regulate ethanol-
related behavior when mutated in vivo, but only a handful have been characterized to date. In this proposal, I
will learn and apply state-of-the-art CRISPR/Cas9 techniques to functionally investigate ethanol-responsive
lncRNA Gas5 for its regulation of ethanol drinking and ethanol-related behaviors.
As ethanol alters gene expression and molecular pathways that regulate neuroinflammation, I want to target an
ethanol-responsive and highly-interconnected competing endogenous RNA (ceRNA) lncRNA that may
coordinate large endogenous immune networks related to AUD.
I will focus on in vivo CRISPR/Cas9 modulation of a specific ‘hub’ lncRNA of interest, growth arrest-specific 5
(Gas5). Gas5 acts as a ceRNA to regulate immune signaling, is significantly and persistently downregulated
following chronic intermittent ethanol vapor exposure and has been shown to reduce cocaine-intake, linking
Gas5 to substance abuse. It is therefore of substantial interest to test the hypothesis that Gas5 is a key
determinant of ethanol action. Gas5 will be knocked out in a temporal, cellular, and brain region-specific manner
to investigate its role on ethanol drinking.
Upon completion of this project, I will have advanced our understanding for the molecular impact of ethanol-
responsive lncRNA Gas5 and how it relates to addictive behavior. This project will provide substantial training
opportunities, a strong research foundation applicable to a variety of scientific fields, and a collaborative
environment with other researchers in the field including the Integrative Neuroscience Initiative on Alcoholism –
Neuroimmune consortium. A wealth of technical skills ranging from bench work to complex surgical techniques,
the understanding and development of project design, and several scientific writing manuscript prospects are
available within each aim that will be valuable for my continued scientific training.

## Key facts

- **NIH application ID:** 10464571
- **Project number:** 1F31AA030176-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sonja Lorean Plasil
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-03-03 → 2023-03-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464571

## Citation

> US National Institutes of Health, RePORTER application 10464571, lncRNA Gas5 dysregulation alters ethanol drinking behavior and ethanol-related phenotypes (1F31AA030176-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10464571. Licensed CC0.

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