Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible disease characterized by shortness of breath and dry cough. IPF scars and stiffens the interstitium, creating a blood-air interface that impairs the lungs’ ability to transfer oxygen and carbon dioxide with each breath. Over time, the lung scarring with IPF worsens, accompanied by cough, breathlessness, and progressively reduced capacity for walking and other activities. Current IPF drug treatments modestly slow the progression of the disease, with lung transplantation the only alternative for long-term survival.
Vanderbilt University Medical Center, the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and the Norton Thoracic Institute at St. Joseph’s Hospital and Medical Center in Arizona have received a $3.5 million federal grant to study the cause of this deadly disease.
“The prognosis of IPF is worse than many cancers,” said Jonathan Kropski, M.D., assistant professor of Allergy, Pulmonary and Critical Care Medicine at Vanderbilt and one of two principal investigators on the study. “Patients with IPF often become progressively more disabled by their lung disease, and today less than half of IPF patients survive five years after their diagnosis.”
New Technology to Aid Investigation
Within the lungs of IPF patients, there are typically areas of both advanced fibrosis and relatively normal lung tissue. It is believed that this “spatial heterogeneity” of IPF features reflect different phases of the disease process. While in the past the patchy nature of the disease presented challenges for analysis, single-cell genomic technologies developed by the study team provide an innovative approach to sample multiple discordantly diseased regions within the same lung.
“With the latest in technology, this work will generate the most comprehensive molecular characterization of healthy and IPF lungs to date. We hope it will answer fundamental questions about cell types, genetic variants and gene expression changes driving the disease,” said Nicholas Banovich, Ph.D., an assistant professor in TGen’s Integrated Cancer Genomics Division.
In the study, Kropski and collaborators will use single-cell sequencing technology to pinpoint gene expression profiles of individual cells within the lungs to identify their function. This will allow the researchers to determine the gene expression programs that drive different phases of disease and examine how genetic factors regulate disease-associated gene programs.
“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,” Kropski said.
“We hope it will answer fundamental questions about cell types, genetic variants and gene expression changes.”
The study is funded by a five-year grant from the National Heart, Lung and Blood Institute of the National Institutes of Health. In addition, the two institutions have received a $2.6 million grant from the Department of Defense to study a variety of other genomic factors associated with non-IPF forms of pulmonary fibrosis.