# Regulation of wound detection in animal tissues

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $402,072

## Abstract

Project Summary
Wounding of epithelial tissue barriers disrupts homeostasis and allows infection. Within minutes, tissues detect
injury and respond by recruiting phagocytes and closing the barrier breach. The signals that activate these early
events are scarcely known, and our overall aim is to identify them. We have used zebrafish, whose wound
responses are close to mammals and easy to image and perturb with genetics and pharmacology, to define early
wound signals. During the last grant cycle, we found that activation of Duox, an H2O2-producing NADPH-oxidase,
and release of a lipid chemoattractant (5-KETE), together are required to attract leukocytes to epithelial wounds.
The molecular mechanisms that integrate NADPH-oxidase activity with lipid chemoattractant production remain
unclear. In parallel, we identified extracellular ATP (eATP) as crucial paracrine mediator of rapid wound closure
through stimulating basal epithelial cell migration in vivo. The molecular mechanisms that convey ATP release
and sensing to promote epithelial repair remain unclear. For the following grant cycle, I propose to investigate
how Duox activity regulates lipid chemoattractant production, and how eATP is released and sensed in live
tissues to mediate rapid epithelial repair. By combining real-time biosensor imaging in live zebrafish with genet-
ics, bioinformatics, biochemistry and chemical biology approaches, we aim to identify and characterize elusive
molecular key players of wound detection in vivo. Our research has strong potential to provide new drug targets
for anti-inflammatory and anti-fibrotic therapy.

## Key facts

- **NIH application ID:** 9994924
- **Project number:** 5R01GM099970-09
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Philipp Michael Niethammer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,072
- **Award type:** 5
- **Project period:** 2012-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994924

## Citation

> US National Institutes of Health, RePORTER application 9994924, Regulation of wound detection in animal tissues (5R01GM099970-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994924. Licensed CC0.

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