# Protease-mediated regulation of stem cell niche remodeling

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $344,946

## Abstract

SUMMARY
Skeletal muscle is the most abundant tissue in the human body, with a wide range of functions, from locomotion
to breathing, vision, blood pressure control, metabolism, and endocrine regulation. Muscle homeostasis and
regeneration are largely dependent on a small population of stem cells that reside quiescent in the muscle tissue
until activated by a stimulus, typically an injury. Tight regulation of the activation process is essential for tissue
homeostasis: too little activation would impair the tissue’s ability to regenerate in response to damage, while too
much activation could lead to tumor formation or premature depletion of the stem cell pool. Neutrophils attracted
to injured muscle secrete proteolytic enzymes, and we have recently observed that one such enzyme, neutrophil
elastase, appears to promote muscle stem cell activation. Moreover, we have observed that triple knockout of
all three neutrophil serine proteases practically abrogates muscle regeneration in response to acute injury. The
overreaching goal of this proposal is to investigate the physiological function of neutrophil serine proteases in
the muscle stem cell niche and decipher the underlying molecular mechanisms. Specifically, our first aim is to
define how the muscle stem cell niche as a whole (cells, matrix and soluble factors) are affected by loss of each
NSP and all three combined. Our second aim is to identify the molecular mechanisms that are regulated in a
cell-autonomous manner by the NSPs in the context of MuSC activation and first division. Finally, our third and
last aim is to validate in vitro and in vivo the candidate biological functions discovered in aim 1 and 2. In
conclusion, we expect that, in addition to answering the main question of which processes and mechanisms
neutrophil serine proteases regulate during muscle regeneration, and how, the results from this work will provide
a platform for future investigations into how stem cell niches are continuously remodeled by proteases to ensure
prompt and efficient regeneration as well as stem cell and tissue homeostasis.

## Key facts

- **NIH application ID:** 10812578
- **Project number:** 1R01AR082593-01A1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Addolorata Pisconti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $344,946
- **Award type:** 1
- **Project period:** 2024-06-19 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812578

## Citation

> US National Institutes of Health, RePORTER application 10812578, Protease-mediated regulation of stem cell niche remodeling (1R01AR082593-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10812578. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*