# Alcohol-mediated Clock genes interfere with lung injury and repair

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $491,796

## Abstract

In the United States, the acute respiratory distress syndrome (ARDS) remains a significant public health
problem. Despite substantial efforts to improve the outcome, ~ 80% of ARDS survivors experience reduced
health-related quality of life and have fibrotic changes on chest imaging for up to 5 years after diagnosis.
Chronic alcohol abuse significantly increases the incidence of, and mortality from, ARDS, without directly
causing lung damage. Emerging data show that alcohol interferes with the circadian signaling pathway in the
liver and intestine which, in turn, render tissue susceptibility to injury and fibrosis. The circadian pathway
consists of multiple transcription factors which mediate various organ physiological functions through its
regulatory networks. It is known that some of circadian pathway molecules can regulate non-coding RNAs and
vice versa, non-coding RNAs can regulate circadian pathway molecules. In this proposal, we present
preliminary data showing that alcohol promotes circadian pathway dysfunction in the lung through alterations of
circadian pathway molecules BMAL1 and nuclear factor Retinoid-Related Orphan Receptor-alpha (RORα). We
believe these changes lead to alcohol-induced TGFβ1 by suppressing RORα-miR-139 activity. Further, we
identified the circ-RORα-miR-155 axis as a novel regulatory mechanism of BMAL1. These results led us to
hypothesize that chronic alcohol ingestion disrupts circadian pathway signaling and the circ-RORα-miR-155
axis which, thereby perturbing the RORα-miR-139 axis which, in turn, render lung susceptibility toward
fibroproliferative disrepair following acute injury. The experimental approaches are designed to test this
hypothesis. These studies will provide a firm scientific basis for the underlying mechanisms by which alcohol
interferes with tissue repair following lung injury.

## Key facts

- **NIH application ID:** 10809019
- **Project number:** 5R01AA029690-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** VIRANUJ SUEBLINVONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $491,796
- **Award type:** 5
- **Project period:** 2023-03-15 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809019

## Citation

> US National Institutes of Health, RePORTER application 10809019, Alcohol-mediated Clock genes interfere with lung injury and repair (5R01AA029690-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10809019. Licensed CC0.

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