# Staphylococcal protease-mediated epithelial barrier perturbation and allergen sensitization

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $654,834

## Abstract

PROJECT SUMMARY/ABSTRACT
Allergies mainly occur in barrier tissues and are driven by the concerted action of the immune and nervous
systems. Following allergen sensitization, overt disease develops when allergen-primed immune effectors are
mobilized to promote inflammation at barrier tissues in response to allergen re-encounter. Barrier dysfunction
is central to the etiology of atopic dermatitis and other allergic diseases. Loss of the barrier integrity not only
permits allergen penetration across the epithelial layer but also prompts a homeostatic-to-inflammatory shift in
epithelial gene expression. Inflammatory signals derived from epithelial cells of barrier-disrupted skin act on
nearby immune cells and nerve endings, dictating their dynamics and function. Skin colonization by
Staphylococcus aureus has emerged as an important feature of atopic dermatitis, yet it remains unclear
exactly how this bacterium contributes to the development of allergic skin disease. The central hypothesis for
the proposed research is that S. aureus colonization drives allergen sensitization and allergic inflammation by
causing skin barrier damage and triggering epithelial inflammatory signaling. Our preliminary data point to a
role for a protease derived from S. aureus in these pathologic processes. To verify this hypothesis, we will
pursue the following specific aims: to determine the role of staphylococcal proteolytic activity in skin barrier
disruption and percutaneous allergen sensitization (Aim #1); to establish the epithelial signaling pathways
linking staphylococcal protease action to the inflammatory gene expression program (Aim #2); and to elucidate
the contribution of staphylococcal protease-activated epithelial signaling to reshaping the skin neuroimmune
landscape and driving allergic skin inflammation (Aim #3). This research project will leverage the
complementary expertise of the participating investigators and technical support from well-established core
facilities. The goal of the proposed research is to decipher the molecular underpinnings of atopic dermatitis and
other diseases linked to barrier dysfunction and translate this knowledge into effective clinical strategies for
their treatment.

## Key facts

- **NIH application ID:** 10878206
- **Project number:** 1R01AI177414-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jin Mo Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $654,834
- **Award type:** 1
- **Project period:** 2024-01-18 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878206

## Citation

> US National Institutes of Health, RePORTER application 10878206, Staphylococcal protease-mediated epithelial barrier perturbation and allergen sensitization (1R01AI177414-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10878206. Licensed CC0.

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