# Decoding microbe-epithelial stem cell interactions in health and disease

> **NIH NIH DP2** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $785,964

## Abstract

Summary
Mammals have formed an evolutionary alliance with the commensal microbes that inhabit our
epithelial boundaries. This lifelong relationship is forged at birth when microbes first colonize our
surfaces. Alterations in neonatal microbial communities are associated with several prevalent
epithelial
skin
dysfunction
interactions
 inflammatory diseases, including atopic dermatitis. Atopic ermatitis is a devastating
disease affecting about 20% of children in the western world and is rooted in epidermal barrier
 and commensal dysbiosis. Yet, surprisingly little s known about the functional
 between colonizing commensals and epithelial populations in neonatal skin.
d
i
Epidermal stem and progenitor cells (ESPCs) maintain the epidermis throughout our lifetime by
taking cues from the microenvironment or “niche”. We recently uncovered a remarkable capacity
for ESPCs to sense, respond to, and remember inflammatory stimuli. Whether and how
commensal signals similarly influence ESPCs and shape epidermal tissue fitness is an open
question.
 Here we address the tantalizing possibility that commensal microbes are a heretofore
unappreciated ESPC niche component. Thus, we aim to illuminate their roles in directing ESPC
differentiation, innate immune activation and, consequently, epithelial barrier function and fitness
in neonates, when microbes first colonize the skin. We also seek to functionally examine how the
early-in-life epithelial–microbe dialogue impacts atopic disease susceptibility. Our proposed use
of genetically tractable commensal strains and epidermal-specific deletion of defined microbial
sensors with a state-of-the art in vivo tissue-specific gene modulation system to systematically
manipulate both host and microbe allows for a comprehensive and mechanistic understanding of
the microbe–ESPC dialogue and its impact on epidermal health and disease. The findings the
generated from these studies will lay the groundwork for developing microbiota-based therapies
to boost the epidermal barrier and mitigate atopic disease.

## Key facts

- **NIH application ID:** 11135141
- **Project number:** 7DP2AR079173-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Shruti Naik
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $785,964
- **Award type:** 7
- **Project period:** 2024-07-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11135141

## Citation

> US National Institutes of Health, RePORTER application 11135141, Decoding microbe-epithelial stem cell interactions in health and disease (7DP2AR079173-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11135141. Licensed CC0.

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