# Signaling mechanisms in muscle regeneration

> **NIH NIH R56** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $372,819

## Abstract

PROJECT SUMMARY
 Understanding the molecular wiring that controls the myogenic process in adult muscle repair and
regeneration will have significant impact on human health issues ranging from muscular dystrophies to disease-
and aging-related loss of regenerative capacity. Work from our laboratory in the last grant cycle has uncovered
novel signaling mechanisms in skeletal myogenesis. Of direct relevance to the current proposal is our most
recent discovery that knockout of ARHGEF3 (a RhoGEF) enhances muscle regeneration in young adult and
aged mice, while also protecting muscle quality during aging. Our findings reveal autophagy as the link between
ARHGEF3 activation of RhoA/ROCK, and muscle regeneration and maintenance. This is the first demonstration
of a role of an endogenous RhoGEF in muscle regeneration/maintenance. We propose studies in the next grant
cycle to investigate the mechanisms of ARHGEF3 regulation in its newly discovered function, which will be
important for the ultimate exploration of therapeutic potential of this new class of regulators.
 With a combination of innovative approaches in biochemistry, cell biology, mouse genetics and muscle
biology, and utilizing both in vitro and in vivo experimental systems, we aim to investigate regulation of ARHGEF3
by PI(4,5)P2 and phosphorylation, as well as crosstalk of those regulatory pathways, in muscle regeneration,
autophagy, and age-dependent loss of regenerative capacity and muscle quality. We will also establish a muscle-
specific CRISPR/Cas9-dependent gene editing mouse model and use it to definitively probe the muscle-
autonomous nature of ARHGEF3 function.
 Our expertise in biochemical characterization of signal transduction mechanisms as well as in muscle
biology, our strong preliminary data, and unique animal models put us in an ideal position to pursue the proposed
studies. Information gained will likely lead to novel mechanistic insights into the regulation of autophagy and
muscle regeneration, and shed light on new therapeutic targets for muscle repair and maintenance of muscle
strength in healthy aging.

## Key facts

- **NIH application ID:** 10477679
- **Project number:** 2R56AR048914-16A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Jie Chen
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $372,819
- **Award type:** 2
- **Project period:** 2003-06-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477679

## Citation

> US National Institutes of Health, RePORTER application 10477679, Signaling mechanisms in muscle regeneration (2R56AR048914-16A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10477679. Licensed CC0.

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