# Origins of Cystic Fibrosis Airway Disease

> **NIH NIH P01** · UNIVERSITY OF IOWA · 2022 · $2,293,311

## Abstract

Twenty-eight years after the discovery of the CFTR gene, the causes of cystic fibrosis (CF) airway
disease remain controversial, we still lack answers to many critical questions, our therapies are
inadequate, and CF remains a life limiting and too often lethal disease. A major impediment to progress
has been lack of CF animal models with a lung disease phenotype resembling humans with CF. We
developed pigs with targeted alterations of the CFTR gene. CF pigs spontaneously develop the hallmark
features of CF lung disease, including airway infection, inflammation, airway wall remodeling, mucus
accumulation, and airway obstruction. Within hours of birth, CF pigs fail to eradicate bacteria as
effectively as wild-type pigs. At least two host defense defects, reduced antimicrobial activity in airway
surface liquid (ASL) and impaired mucociliary transport (MCT) contribute. Both were caused by
abnormally acidic airway liquid. In this Program three highly accomplished investigators will use CF pigs
to answer fundamental questions about CF lung disease. Together, the three projects will discover how
loss of CFTR function affects: a) submucosal gland function, the properties of mucus, and MCT; b) ASL
pH and proton secretion via ATP12A; and, c) small airways function, a likely site of CF disease
pathogenesis. The Project Leaders and their teams have an outstanding track record of collaborative CF
research, and here they sharpen their focus to a common goal. Their highly creative research is
supported by five cores that provide innovative infrastructure and services. By further educating CF
pathogenesis, it will accelerate discovery of novel therapies for this lethal disease.

## Key facts

- **NIH application ID:** 10470203
- **Project number:** 5P01HL091842-15
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** DAVID A STOLTZ
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,293,311
- **Award type:** 5
- **Project period:** 2008-09-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470203

## Citation

> US National Institutes of Health, RePORTER application 10470203, Origins of Cystic Fibrosis Airway Disease (5P01HL091842-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10470203. Licensed CC0.

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