# Molecular mechanisms underlying optimal glucocorticoid therapy for vocal fold disease

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $211,875

## Abstract

PROJECT SUMMARY
The goal of this proposal is to determine the type of glucocorticoids (GCs) that fosters the appropriate balance
of anti-inflammatory and fibrotic gene expression in pre-clinical models of vocal fold injury to improve outcomes
of GC therapy. GCs are used by otolaryngologists in office-based procedures to treat vocal fold disease to
reduce inflammation and promote effective wound healing, yet the optimal GC treatment regimen isn’t known.
Ideal GC therapy for laryngeal disease would not only suppress inflammation but would also induce fibroblasts
to promote laryngeal healing without excessive fibrosis that leads to scaring, vocal impairment, and poor
outcomes.
Our preliminary studies demonstrate that in vocal fold fibroblasts there are significant differences in the GC
type and concentration required to activate pro-fibrotic genes and repress pro-inflammatory genes by GR. We
hypothesize that such variability in gene expression among the three different clinically used GCs is likely to
reflect divergent GR DNA binding capacity and/or interactions with co-regulator molecules (e.g. transcriptional
co-activators and co-repressor). We further propose that understanding the type of GC that fosters the correct
balance of anti-inflammatory and fibrotic gene expression in pre-clinical models of vocal fold injury will improve
outcomes of GC therapy. To test these hypotheses we will determine the effects of three commonly employed
GCs on GR-dependent gene expression, GR chromatin occupancy, and GR chromatin-associated proteins in
vocal fold fibroblasts, and evaluate the mechanisms underlying GC therapy following iatrogenic injury in vivo.
Successful completion of the aims will provide the pre-clinical foundation for optimized GC therapy among
clinically common GCs.

## Key facts

- **NIH application ID:** 10840435
- **Project number:** 5R21DC021054-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ryan Comfort Branski
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2023-05-11 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840435

## Citation

> US National Institutes of Health, RePORTER application 10840435, Molecular mechanisms underlying optimal glucocorticoid therapy for vocal fold disease (5R21DC021054-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10840435. Licensed CC0.

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