# Molecular Mechanism of Human Myogenesis

> **NIH AR R01** · UNIVERSITY OF GEORGIA · 2026 · $614,390

## Abstract

Myoblast fusion is essential for muscle development and regeneration. The long-term goal of our
research is to identify key molecular regulators of this process, focusing on the role of CHAMP1
gene in CHAMP1 syndrome—a severe developmental disorder characterized by muscle
weakness, hypotonia, and motor impairments, often requiring lifelong care. Our CRISPR-based
screening, developed with R21 funding, identified CHAMP1 as a novel regulator of human
myoblast fusion. We discovered a noncanonical function of CHAMP1 as a MyoD co-factor that
promotes fusion by inducing the expression of muscle fusogen Myomaker. Deletion of CHAMP1
in patient cells and mouse models leads to impaired myoblast fusion, reduced Myomaker
expression, and phenotypes resembling Myomaker-null conditions. To build on these findings, we
aim to thoroughly investigate CHAMP1’s role in muscle development and function in vivo, utilizing
tissue- and stage-specific mouse models that target both embryonic muscle precursors and adult
myofibers. This involves detailed molecular and phenotypic analyses, assessing muscle
morphology and functional performance. We will also leverage an unique transplantation model
and employ the newest spatial transcriptomics tools to unbiasedly assess the consequence of
patient mutations on human myoblast fusion. By this project, we will also elucidate the
biochemical mechanisms by which CHAMP1 regulates Myomaker expression, focusing on its zinc
finger motifs and interaction with the MyoD:TCF12:P300 complex. Our approach integrates RNA
sequencing, CUT&Tag assays, protein interaction studies, and AlphaFold3-based structural
modeling to map protein interfaces at the atomic level. Upon completing this study, we will not
only gain critical insights into how CHAMP1 mutations cause fusion myopathy but also establish
new animal models and molecular targets for studying and treating muscle symptoms in CHAMP1
syndrome. This project will benefit CHAMP1 patients in three distinct venues: 1)

## Key facts

- **NIH application ID:** 11279729
- **Project number:** 1R01AR087085-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Pengpeng  Bi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AR
- **Fiscal year:** 2026
- **Award amount:** $614,390
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2031-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11279729

## Citation

> US National Institutes of Health, RePORTER application 11279729, Molecular Mechanism of Human Myogenesis (1R01AR087085-01). Retrieved via AI Analytics 2026-05-17 from https://api.ai-analytics.org/grant/nih/11279729. Licensed CC0.

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