Bradley H. Rosen, DO, assistant professor in Pulmonary, Critical Care, and Occupational Medicine is the principal investigator on a four-year, $245K collaborative U01 subaward with the NIH’s National Heart, Lung, and Blood Institute. Rosen will lead the University of Iowa’s effort to understand the pathobiological mechanisms that lead to idiopathic pulmonary fibrosis (IPF).
IPF is an incurable, chronic interstitial lung disease characterized by aberrant scar tissue formation that can rapidly progress to respiratory failure. A major risk factor for developing IPF is a commonly found gain-of-function mutation in the promoter of the respiratory mucin, Muc5B, that leads to excess expression. However, the mechanism by which this leads to disease is not well understood, in part due to limitations of existing models of lung disease that have not been able to replicate the persistent and progressive disease seen in the human condition. Ferret lung biology is highly conserved and this has enabled their ability to model cystic fibrosis, chronic bronchitis, and emphysema. Providing the foundation for this project, the ferret Muc5B promoter sequence and sources of Muc5B protein are similar to that seen in the human airways.
Rosen will work closely with his collaborator Steven Rowe, MD, professor of Medicine at the University of Alabama at Birmingham (UAB), to generate and use ferret models to dissect the role of Muc5B in this progressive pulmonary disease. This multi-site collaborative project will harness a combination of genetic and pharmacological methods to modulate the expression of native Muc5B in the ferret lung. The project aims to test the overarching hypothesis that heightened Muc5B expression directly promotes aberrant repair mechanisms that lead to fibrosis and thus could become a therapeutic target.