# Unmasking p38 MAPK Functions in Lysosome Homeostasis during Development and Aging

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $451,000

## Abstract

Project Summary
Compromised tissue integrity is a major cause of debility during aging. Emerging findings suggest critical
functions of lysosomes promoting tissue integrity. Our unpublished findings indicate key roles for C. elegans
PMK-1, a conserved p38 MAPK member, in promoting lysosome formation and tissue integrity during
development and aging. These non-cell autonomous functions signal between germline, epidermis and
nerve. Moreover, our data indicate that p38 MAPK acts on distinct targets in a tissue-specific and stage-
specific manner to promote lysosome function. It is not known how p38 MAPK signals between tissues to
coordinate lysosome function. We hypothesize that PMK-1 promotes lysosome function by signaling a cell
non-autonomous network regulating the regeneration and heterogeneity of lysosomes across tissues. Over
the next 2 years, the critical goals for this project are to: 1) define the PMK-1 interactome required for
lysosome regeneration, 2) reveal tissue and stage-specific functions of PMK-1 in lysosome regeneration
and heterogeneity, and 3) delineate tissue-specific contributions to PMK-1 cross-tissue signaling. We have
built an array of tools to deeply understand how p38 signaling regulates lysosome regeneration and
heterogeneity to promote tissue integrity. Our proposed interdisciplinary studies include proteomics, genetic
screens, biochemical analyses, and cell biology approaches to tackle this complex problem of
understanding non-cell autonomous p38 MAPK function. The long-term objective of the proposed studies is
to understand the molecular and physiological mechanisms of p38 MAPK signaling in tissue integrity during
development and aging.

## Key facts

- **NIH application ID:** 10988328
- **Project number:** 1R21AG086710-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Benjamin P. Weaver
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988328

## Citation

> US National Institutes of Health, RePORTER application 10988328, Unmasking p38 MAPK Functions in Lysosome Homeostasis during Development and Aging (1R21AG086710-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10988328. Licensed CC0.

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