VUMC and TGen receive $6.1 million in grants to study deadly lung disease

The Translational Genomics Research Institute (TGen), an affiliate of City of Hope, along with Vanderbilt University Medical Center (VUMC) and the Norton Thoracic Institute at St. Joseph’s Hospital and Medical Center in Arizona, have received a $3.5 million federal grant from the National Institutes of Health to study the cause of Idiopathic Pulmonary Fibrosis (IPF) the nation’s most common and severe form of fibrotic lung disease.

In addition, TGen and VUMC have received a $2.6 million federal grant from the Department of Defense (DOD) to study a variety of other genomic factors associated with non-IPF forms of pulmonary fibrosis (PF).

IPF is a progressive and irreversible disease characterized by shortness of breath and a dry cough. IPF and PF both scar and stiffen the interstitium — the delicate lace-like network that supports the lungs’ tiny air sacs. Microscopic blood vessels weave through the interstitium, creating a blood-air interface that allows oxygen to be pulled into the blood with each inhale, and carbon dioxide to be expelled into the air with each exhale.

An estimated 50,000 Americans, mostly middle-aged and older adults, are diagnosed each year with IPF. Most die from respiratory failure within five years.

There currently is no known cause, no cure and no treatment to improve patient lives short of a lung transplant, a radical surgery that usually requires months of waiting for available organs, and often requires a long and sometimes agonizing recovery. Current IPF drug treatments only slow the progression of the disease.

“With the latest in technology, this work will generate the most comprehensive molecular characterization of healthy and IPF lungs to date, and promises to answer fundamental questions about cell types, genetic variants and gene expression changes driving the disease,” said Nicholas Banovich, PhD, an assistant professor in TGen’s Integrated Cancer Genomics Division, and the leader of the study team along with Jonathan Kropski, MD, assistant professor of Medicine and Cell and Developmental Biology at VUMC.

With new single-cell sequencing technology adopted by the TGen and Vanderbilt investigators, Banovich, Kropski and their collaborators are now able to closely examine the gene expression profiles of individual cells within the lungs to identify their function, and ultimately understand the gene changes that may be driving the disease.

Prior to the advent of single-cell sequencing devices, researchers could not begin to decipher the molecular source of IPF, Banovich said. By closely examining individual cells, rather than a mash-up of many cells from a tissue sample, researchers anticipate being able to identify specific gene expression changes that could lead to IPF. This could result in earlier diagnosis and perhaps better treatments for the disease.

“By improving our understanding of the critical molecular drivers of IPF, we are very hopeful that these studies will set us on a path to more precise and more effective treatments that improve the lives for the hundreds of thousands of patients with this disease,” Kropski said.

While IPF is the most common form of fibrotic lung disease, many individuals are affected by a variety of other forms of PF. The DOD grant to study non-IPF lung fibrosis will complement the first study by closely examining the other mechanisms that cause scarring and stiffening in the interstitium.

“Together both grants will help us to closely examine all lung tissue and search for the genomic factors that drive all pulmonary fibrosis,” Banovich said. “Since IPF represents about 20 percent of all lung fibrosis, the second grant from DOD will help allow us to characterize the many different genomic drivers of the other 80 percent of patients with lung fibrosis, potentially giving us a more universal assessment of lung disease and how best to treat these debilitating conditions.”

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