# Alcohol-induced myomiR dysregulation: mechanisms of impaired skeletal muscle regeneration in SIV/HIV

> **NIH NIH K01** · LSU HEALTH SCIENCES CENTER · 2020 · $166,322

## Abstract

Project Summary/Abstract
The objective of this NIH Mentored Research Scientist Development Award (K01) application is to provide
additional training and research skill sets in three critical areas needed to conduct high priority research in
HIV/AIDs-associated comorbidities. Specifically, the candidate will be skilled to conduct basic and
translational research focused on the alcohol-mediated metabolic complications prevalent in the
prematurely aged individuals infected with HIV on antiretroviral therapy. The applicant is a promising
scientist with a track record of research in stem cells and signaling, which she now proposes to integrate
with the field of alcohol-induced epigenetic alterations. The integrated and comprehensive plan to develop
research skills will build the candidate’s expertise in epigenetic analysis, biostatistics, and translational
research. The research proposal will focus on elucidating the mechanisms of alcohol-induced impairment
of skeletal muscle (SKM) regeneration in SIV/HIV. Myoblasts isolated from chronic binge alcohol (CBA)-
administered macaques show decreased myogenic gene expression and potential to differentiate into
myotubes when cultured in vitro. Impaired myogenic differentiation was observed in the absence of in
vitro alcohol exposure, suggesting that these myoblasts had a “memory” that preserved gene expression
changes. Preliminary evidence also suggests dysregulated muscle-specific microRNAs (myomiRs) in the
SKM of CBA-administered SIV-infected macaques leading to the hypothesis that CBA impairs SKM
regeneration in SIV/HIV infection through epigenetic modifications of myogenic gene transcription. This
hypothesis will be critically tested by three specific aims. The first aim will test the prediction that CBA
results in decreased myoblast myomiR expression and differentiation potential. To address this, the
candidate will use her existing skills in stem cell culture and molecular techniques. In addition, she will be
trained in in situ hybridization techniques for determining expression of myomiRs in myoblast cultures. The
second aim will test the prediction that CBA-induced myoblast histone modifications contributes to
decreased myogenic differentiation potential. Using molecular techniques target genes of myomiRs will be
validated, histone deacetylase (HDAC) activity, and histone modifications will be determined. The third aim
will establish the clinical relevance of altered myomiR expression in the circulation in a cohort of persons
living with HIV/AIDS ( P L W H A ) with alcohol use disorders (AUD). Circulating levels of myomiRs will be
correlated with AUD and muscle strength (hand grip dynamometer) to establish their potential use as
indicators of impaired myogenic function. The overarching goal of the proposed and future studies is to identify
targets to improve skeletal muscle function using physical (exercise) or pharmacological interventions. The
integrated translational and transdisciplinary training...

## Key facts

- **NIH application ID:** 9976400
- **Project number:** 5K01AA024494-05
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Liz Simon
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $166,322
- **Award type:** 5
- **Project period:** 2016-07-05 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976400

## Citation

> US National Institutes of Health, RePORTER application 9976400, Alcohol-induced myomiR dysregulation: mechanisms of impaired skeletal muscle regeneration in SIV/HIV (5K01AA024494-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9976400. Licensed CC0.

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