# Translational Program in CFTR-Related Airway Diseases

> **NIH NIH R35** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $917,966

## Abstract

PROJECT SUMMARY / ABSTRACT
Cystic fibrosis transmembrane conductance regulator (CFTR) maintains epithelial function by
acting as an ion channel at the apical surface of epithelial cells, and governs the formation of
mucus and its clearance. Genetic mutations of CFTR cause CF, and these mutations also
contribute to other airway diseases by altering host defense. We have helped discover that
CFTR dysfunction also can be acquired in the absence of congenital mutations, contributing to
the pathogenesis of the chronic bronchitis phenotype of chronic obstructive pulmonary disease
(COPD). To this aim, this Research Program will make decisive advancements in elucidating
the pathogenesis of airway diseases linked to genetic and acquired CFTR dysfunction, and will
apply this knowledge to develop new tools for their diagnosis and treatment. The Program will
encompass two focus areas critical to the mission of the NHLBI. The first will tackle fundamental
questions surrounding mucus clearance, using CF as the model. We will implement in vivo
μOCT imaging, a technique we co-invented that provides an unprecedented view of the
functional microanatomy of the airway surface; perform innovative techniques to probe airway
mucus; and use a novel CF rat that exhibits delayed mucus clearance and an inherit defect in
host defense that develops over time to 1) illuminate mechanisms governing the formation of
mucus and its clearance, 2) develop novel therapeutic approaches targeting abnormal mucus
itself, and 3) establish mechanisms underlying increased susceptibility to chronic bacterial
infection and novel strategies for bacterial eradication. In the second focus area, we will study
the role of these pathways in chronic bronchitis, a prevalent disorder that lacks treatments that
reverse its natural history. We will determine 1) the impact of acquired CFTR dysfunction in
ferrets, the first animal model of chronic bronchitis, 2) mechanisms of mucus stasis in the
human COPD airway (and contrast with CF), 3) whether acquired CFTR dysfunction increases
susceptibility to chronic bacterial infection or respiratory exacerbations in COPD ferrets, and 4)
test novel therapies for chronic bronchitis, including advancing CFTR potentiators for this
indication. There will be significant synergy between these studies, which will not only employ
cutting-edge techniques and animal models but also take advantage of our recognized expertise
in leading first-in-class human investigation into CFTR-directed therapies. Noting Dr. Rowe's
consistent track record of successes; the innovative, one-of-a-kind capabilities of his laboratory;
and the immediate feasibility of proposed objectives, this Program promises to transform the
field and uncover treatments that offer momentous improvements to duration and quality of life.

## Key facts

- **NIH application ID:** 10076630
- **Project number:** 5R35HL135816-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Steven Mark Rowe
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $917,966
- **Award type:** 5
- **Project period:** 2017-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076630

## Citation

> US National Institutes of Health, RePORTER application 10076630, Translational Program in CFTR-Related Airway Diseases (5R35HL135816-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10076630. Licensed CC0.

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