# Epithelial innate signaling in airway inflammation and remodeling

> **NIH NIH P01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $1,754,585

## Abstract

Respiratory Syncytial Virus (RSV) is a leading cause of childhood respiratory disease, responsible for 75,000–
125,000 hospitalizations annually and producing significant morbidity and economic impact. No vaccine is
currently licensed to prevent RSV infections. Children hospitalized for RSV lower respiratory tract infections
(LRTIs) have reduced pulmonary function, a significant predictor of adult chronic lung disease. This is a
competing renewal for our P01, originally funded as AADCRC AI46004 and subsequently through two P01
cycles (9/1/2005-present). Work in our P01 has elucidated mechanisms by which RSV infection produces a
rapid epithelial oxidative stress response, triggering innate signaling and resulting in cytokine secretion that
triggers and shapes adaptive immunity. More recently, we have developed additional compelling evidence
supporting the central theme of this P01 – that innate inflammation produced by infection with the ubiquitous
viral pathogen RSV impairs antioxidant capacity, producing disease and triggering long-term airway
remodeling. Our projects are developed from original discoveries by our internationally recognized project
leaders (PLs) expert in innate inflammation, oxidative stress, and the DNA damage response. Our renewal
includes three major research projects (RPs): 1) RP1 (“Epigenetic regulation of innate inflammation-driven
airway remodeling”) will focus on the role of the NFκB-coactivator, a chromatin remodeling complex (CRC)
nucleated by bromodomain-containing protein 4 (BRD4) in RSV-induced remodeling via epithelial-
mesenchymal transition and myofibroblast expansion; 2) RP2 (“The role of innate immunity in
downregulation of the airway antioxidant response during paramyxovirus infection”) will focus on how
RSV causes disease mediated by unbalanced ROS production via a progressive decrease in NF-E2-related
factor 2 (NRF2); and 3) RP3 (“Linkage of the oxidant induced OGG1-DNA complex to airway
inflammation and remodeling”) will test the hypothesis that RSV-induced epigenetic modification via
oxidation of guanine to oxoG in gene regulatory regions controls acute/chronic inflammation and airway
remodeling via the NFκB pathway. This P01 is guided by regular and sustained interactions with our Internal
and External Advisory Committees and is nurtured by significant institutional support from UTMB Centers,
Departments, and Institutes. All our inter-related and synergistic RPs are supported by an Administrative Core,
and human subjects and viral preparations from the Infant Bronchiolitis and Viral Core (IBVC). Translational
advances include applications of BRD4 inhibitors, NRF2 agonists, and OGG1 inhibitors that in preclinical
studies show promise to interfere with RSV-induced inflammation and remodeling. Upon completion, this P01
will have identified mechanisms of innate signaling-induced remodeling and developed strategies for reversing
remodeling and restoring defective innate immunity in allergic airway diseases.

## Key facts

- **NIH application ID:** 9974462
- **Project number:** 5P01AI062885-13
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Roberto P Garofalo
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,754,585
- **Award type:** 5
- **Project period:** 2004-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974462

## Citation

> US National Institutes of Health, RePORTER application 9974462, Epithelial innate signaling in airway inflammation and remodeling (5P01AI062885-13). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974462. Licensed CC0.

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