# Defining the role of respiratory gland patterning in rhinosinusitis

> **NIH NIH R00** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $108,097

## Abstract

Project Summary
 This project summary pertains to the Supplement. Rhinosinusitis (RS) is one of the most prevalent airway
diseases, effecting approximately 15% of the U.S population. With symptoms of sinonasal mucus hypersecretion
and plugging, severe facial pain and breathing difficulties, RS significantly affects both quality of life and
socioeconomic burden. Despite these dire outcomes, the etiology of RS is completely unknown, severely
hampering the development of preventative or curative treatments.
 In the parent grant, we investigate how aberrant patterning of the nasal submucosal glands (SMGs), may
be causative for chronic RS (CRS, > 12 weeks). Based on the high penetrance of CRS in patients with mutations
in cystic fibrosis transmembrane conductance regulator (CFTR) gene (Cystic Fibrosis) and studies showing
aberrant SMG morphology and function are common to this disease, this proposal tests the hypothesis that
dysfunction in CFTR leads to aberrant SMG patterning and thus, CRS. This hypothesis will be tested via three
specific aims. (1) Define cell identities, lineage dynamics and cell-cell signaling networks during SMG
development. In this Aim, transcriptomic techniques and quantitative measures of morphological changes will
be employed to uncover processes governing human SMG development, which can then be utilized to delineate
mechanisms of disease SMG patterning. (2) Elucidate CFTR dysfunction in SMGs as an underlying cause
of CRS. This Aim will use the murine mouse model to test the hypothesis that mis- regulation in CFTR is a cause
of tissue remodeling and CRS. (3) Identify molecular and cellular signatures of SMG remodeling in human
adult CRS. This final aim will examine morphological and transcriptomic gland phenotypes common to healthy,
eosinophilic CRS without polyps, and eosinophilic CRS with nasal polyps, providing insight into alterations in
gland structure and function, and thus contribution to different CRS pathologies.
 In this Diversity Supplement application, we build on our subsequent studies that have established the
emergence of nasal ionocytes during early SMG morphogenesis, with an enrichment of these cells in SMG ducts.
We confirm that Cftr expression is highly expressed in embryonic ionocytes and epithelial specific deletion of
Cftr significantly reduces ionocyte identity regulator genes. To this end, we hypothesize that CFTR regulates
ionocyte differentiation and SMG development. To test this, we will build on our AIM 1 and AIM 2 of the parent
grant and scrutinize the role of CFTR in ionocyte specification and airway SMG signaling mechanisms, at a
single cell resolution. Outcomes will determine how CFTR mediates ionocyte emergence and how this
contributes to aberrant SMG morphogenesis.

## Key facts

- **NIH application ID:** 11100364
- **Project number:** 3R00HL145094-05S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Alison May
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $108,097
- **Award type:** 3
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11100364

## Citation

> US National Institutes of Health, RePORTER application 11100364, Defining the role of respiratory gland patterning in rhinosinusitis (3R00HL145094-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11100364. Licensed CC0.

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