Twenty-three years after identification of the CFTR gene, controversies still surround the pathogenesis of airways disease, we lack answers to many crucial questions, current treatments are inadequate, and cystic fibrosis (CF) remains a life shortening and too often lethal disease. A major impediment to progress has been lack of a CF animal model other than the mouse. CF mice fail to develop lung disease, the cause of most CF morbidity and mortality. We have now 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. In this Program three senior and highly accomplished investigators will seize the unique opportunity to use CF pigs to answer key questions about CF lung disease. Together, the three projects will discover how loss of CFTR function affects: a) mucociliary transport;b) the response of airways to viral infection;c) HCO3- secretion and control of airway surface liquid pH;and d) bacterial killing on the airway surface. The Project Leaders have an outstanding track record of collaboration in CF, and here they sharpen their focus to a common goal. Their research is highly creative and is supported by five cores that provide innovative services and infrastructure. Discoveries from this PPG will accelerate development of novel therapies for patients who suffer from this devastating disease.

Public Health Relevance

The three projects will discover how loss of CFTR function affects: a) mucociliary transport;b) the response of airways to viral infection;c) HCOa'secretion and control of airway surface liquid pH;and d) bacterial killing on the airway surface.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01HL091842-07
Application #
8737935
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Program Officer
Smith, Robert A
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Iowa
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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