Major Grant Enhances Pulmonary Fibrosis Research

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Vanderbilt University Medical Center (VUMC) has received an $11 million program project renewal grant from the National Heart, Lung and Blood Institute to study the genetics and underlying biological mechanisms that lead to idiopathic pulmonary fibrosis (IPF).

IPF causes lung tissue to become thick and stiff over time, prohibiting the lungs from properly circulating oxygen into the bloodstream. With limited treatment options available, survival is three to five years after diagnosis.

Timothy Blackwell, M.D., Ralph and Lulu Owen Professor of Medicine, has been studying IPF for the past 15 years. This grant renewal will help his research group, which includes John Phillips III, M.D., David T. Karzon Professor of Pediatrics and director of the Division of Medical Genetics and Genomic Medicine in Pediatrics, and David Schwartz, M.D., professor and chair of the Department of Medicine at the University of Colorado, better understand the genetics of IPF, which affects approximately 50,000 adults over the age of 65 in the United States.

Blackwell and James Loyd, M.D., the Rudy W. Jacobson Professor of Pulmonary Medicine, are core leaders for the program project grant. Other key contributors to the program include Joy Cogan, Ph.D., William Lawson, M.D., Jonathan Kropski, M.D., Lisa Young, M.D., and John Worrell, M.D.

“This has been a really successful program so far; it’s unique in the field,” Blackwell said. “Ours is the only large study looking at the genetics of pulmonary fibrosis in the country. The work by Jim Loyd and our study coordinators, Cheryl Markin and Errine Garnett, along with the efforts of our collaborators in Denver, have enabled us to enroll and follow more families with IPF than any other group in the world. We have this really unprecedented opportunity to try to understand the genetics of this disease.”

The IPF team has established a database in collaboration with the University of Colorado that contains genetic information on more than 1,200 families.

The grant will fund various research projects related to genetic discovery, understanding the function of new gene mutations and looking at how the genetics influence the biology and histologic changes that take place with disease progression in both familial and sporadic IPF.

“We’ve made real progress in terms of identifying new genes that cause disease in families. We recently published one new gene that accounts for about 5 percent of all the cases, and we’re working on several other genes that we’ve identified in specific families that are associated with disease,” Blackwell said.

It is estimated that 10 to 20 percent of IPF cases may be familial and the familial disease has been linked to several genes in two gene families. However, the genetic contributors in the majority of families have not been discovered yet.

“Familial pulmonary fibrosis is a jigsaw puzzle with lots of small pieces. We think these small pieces of individual genes are going to fit into a few pathways within gene families. If we can validate enough of these genes present in small number of families, the picture will start to take shape and it will be much clearer how to identify culprit mutations in other families,” Blackwell said.

Additionally, the IPF research group will strive to understand the natural history of the disease by studying people who are asymptomatic but have relatives with the disease.

“If we could start to identify the factors that predict progression to clinical disease in asymptomatic people, that would offer us a chance to do early detection and prevention,” Blackwell said.