# Fbxw7 as a target to promote muscle stem cell expansion

> **NIH NIH R21** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $214,500

## Abstract

SUMMARY
The goal of this proposal is to define novel approaches to promote muscle stem cells (MuSC) expansion. MuSC
are the major source of skeletal muscle growth and regeneration. This cell population is capable of self-renewal,
i.e. generating large number of progenitors to repair damaged tissue and at the same time more copies of
themselves upon cell division to maintain the stem cell pool. MuSC exist in healthy adult tissues in a quiescent
state, and upon stress or injury they are activated to proliferate and repair the damaged tissue. While this process
is efficient in healthy conditions, in several diseased states and during aging the function of MuSC is impaired
and this significantly contribute to impaired tissue maintenance and function. However, their clinical utility as
therapeutic tools and targets is currently hindered by our limited understanding of the molecular networks
regulating their function. Thus, there is a major need to fill this gap and define novel approaches that can promote
MuSC expansion and tissue repair, as these would find applications for disease modeling in vitro as well as for
promoting MuSC-mediated tissue regeneration in chronic conditions. Our preliminary results provide evidence
that the E3 ubiquitin ligase Fbxw7, which regulates multiple adult stem cell compartments, promotes MuSC
commitment and differentiation, and its genetic ablation leads to robust MuSC expansion in vivo. The focus of
the proposed studies is to dynamically map Fbxw7 protein targets during MuSC fate transitions, and to
evaluate its transient inhibition as a novel approach to promote MuSC expansion. Our research will take
advantage of (1) the inducible Pax7-CreER;Fbxw7f/f novel animal model, (2) an optimized global proteomics
approach for MuSC profiling, (3) the use of Fbxw7 inhibitors for its transient manipulation, and (4) Human MuSC
isolated from patients, to validate conservation across species. Together, this exploratory study will provide an
initial understanding of how Fbxw7 impacts MuSC cell fate decisions and identify novel tools that can be utilized
for regenerative medicine approaches to enhance MuSC expansion and tissue repair in diseased conditions.

## Key facts

- **NIH application ID:** 9896756
- **Project number:** 5R21AR075205-02
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Alessandra Sacco
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $214,500
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896756

## Citation

> US National Institutes of Health, RePORTER application 9896756, Fbxw7 as a target to promote muscle stem cell expansion (5R21AR075205-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9896756. Licensed CC0.

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