Rosen awarded CFF career development grant

Bradley H. Rosen, DO, assistant professor of Internal Medicine in Pulmonary, Critical Care, and Occupational Medicine has been named a Harry Shwachman Clinical Investigator awardee by the Cystic Fibrosis Foundation. This prestigious award is designed to provide the opportunity for promising, clinically trained physicians with a commitment to research to develop into independent cystic fibrosis (CF) biomedical researchers. This K-equivalent, three-year $100,000 award will provide salary support, travel funds, and a modest supply budget.

Rosen will continue his recent CF work in the cystic fibrosis transmembrane regulator (CFTR)-null ferret model under the mentorship of John Engelhardt, PhD, and Pulmonary Division Chief Joseph Zabner, MD, PhD. Rosen’s work has shown that, although CF-related infection can be prevented using preemptive lifelong antibiotics, mucoinflammatory lung disease still develops. However, the development occurs at a slower pace when compared with CF animals given conventional symptom-triggered antibiotic therapy. This suggests that in the absence of functional CFTR, there is an innate and inevitable tendency toward lung disease and infection accelerates this process.

More recent work published this year demonstrated that delivering ivacaftor in utero to ferrets with a specific CFTR genetic mutation prevented the development of CF disease in the lung, pancreas, and intestine. Further studies revealed that administration of ivacaftor only after CF ferrets were born did not offer the same protections. Moreover, when ivacaftor therapy was stopped, the CF ferrets developed lung disease before bacterial infection was detected, suggesting that CF-related mucus accumulation and inflammation occur early in CF lung disease.

Using this ivacaftor-responsive ferret Dr. Rosen will build on the hypothesis that in the CF lung, dysregulated mucin subtypes contribute to the initiation and propagation of mucoinflammatory lung diseases. He will test this using various novel transgenic ferrets and a CRISPR/Cas9 gene editing approach in airway stem cell cultures. Because excess and persistent mucus is a feature of other lung diseases such as COPD and asthma in addition to CF, Dr. Rosen’s discoveries in this work may help further understanding of these conditions and inform new approaches for treatment.

Read more about the Harry Shwachman Clinical Investigator Award and other CFF career development grants.

 

 

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