UI cystic fibrosis research team wins $11.5 million NIH grant renewal
A University of Iowa research team has been awarded a five-year, $11.5 million grant from the National Institutes of Health to continue its work on identifying and developing treatment for the causes of cystic fibrosis (CF) lung disease.
This is the second renewal for this major project grant, first funded in 2008 under the leadership of Michael Welsh, MD, professor of internal medicine and director of the Pappajohn Biomedical Institute. With this renewal, David Stoltz, MD, PhD, professor of internal medicine, takes the helm as principal investigator with Welsh, Paul McCray, MD, professor of pediatrics, and Joseph Zabner, MD, professor of internal medicine and director of the Division of Pulmonary, Critical Care and Occupational Medicine, continuing as project investigators.
The UI team is uniquely situated to make progress on the fundamental questions about CF lung disease that still remain despite the discovery 29 years ago of the CFTR gene that causes the disease. An early barrier to discovery was the lack of an animal model of CF lung disease. Mice are the ubiquitous animal model system for medical research, but mice with CF don’t get lung disease. To overcome this barrier, the UI team developed a pig model of CF in 2008 that for the first time provided a research avenue for CF lung disease.
The pig model has been key to determining the impact of acidity in CF lung disease. The thin layer of liquid covering the airway surface is more acidic in CF lungs. This impairs airway killing of bacteria and alters the ability to clear mucus from the lungs. These disruptions make CF lungs particularly susceptible to airway infection, a major cause of disease and death in CF.
Now the team proposes to take the next steps.
“We will be developing new therapeutics based on our earlier discoveries and continuing our study of the basic pathogenesis of CF airway disease with a new focus on small airways and the role of viruses,” Stoltz says. “We hope to have an important positive impact on accelerating discovery of new therapeutic interventions and endpoints for early CF.”
The research team includes UI faculty: Mahmoud Abou Alaiwa, MD, assistant professor of internal medicine; Alejandro Comellas, MD, clinical associate professor of internal medicine; John Engelhardt, PhD, professor of anatomy and cell biology; Anthony Fischer, MD, PhD, assistant professor of pediatrics; Eric Hoffman, PhD, professor of radiology; Xiaopeng Li, PhD, research associate professor of internal medicine; David Meyerholz, DVM, PhD, professor of pathology; Lynda Ostedgaard, PhD, research professor of internal medicine; Alejandro Pezzulo, MD, assistant professor of internal medicine; Patrick Ten Eyck, assistant director for biostatistics and research design, Institute for Clinical and Translational Science. External collaborators include: Michael Duffey, PhD, professor of physiology and biophysics, State University of New York, Buffalo; Biao He, PhD, University of Georgia Research Foundation, Randall Prather, PhD, Director, National Swine Resource and Research Center, University of Missouri; Kevin Wells, PhD, associate professor of animal sciences, University of Missouri.