The Translational Genomics Research Institute (TGen), an affiliate of City of Hope, has received a total of $6.1 million in two grants to study deadly lung diseases that affect hundreds of thousands of Americans, and for which there are no cures.
“In their late stages, these are horrific diseases that leave patients literally gasping for life,” said Dr. Nicholas Banovich, an Assistant Professor in TGen’s Integrated Cancer Genomics Division. “I originally became interested in studying Idiopathic Pulmonary Fibrosis (IPF) after watching a friend suffer through this disease. I knew then that we must find new and better ways to help these patients.”
Along with Vanderbilt University Medical Center (VUMC), and the Norton Thoracic Institute at Dignity Health St. Joseph’s Hospital and Medical Center, TGen received a $3.5 million federal grant from the National Institutes of Health (NIH) to study the cause of IPF, the nation’s most common and severe form of fibrotic lung disease. 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.
In addition, TGen and VUMC 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 a dry cough, fatigue, aching muscles and joints, and ever worsening shortness of breath. 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.
IPF has no known cause and current treatments short of a lung transplant only slow disease progression. Lung transplants are radical surgeries that usually require months of waiting for available organs, and often require a long and sometimes agonizing recovery.
Investigators plan to use single cell sequencing to generate a more comprehensive understanding of IPF at the genomic level.
“Our hope is to generate the most comprehensive molecular characterization of healthy and IPF lungs to date. This study promises to answer fundamental questions about cell types, genetic variants, and gene expression changes driving the disease,” said Dr. Banovich, the leader of the study team, along with Dr. Jonathan Kropski, Assistant Professor of Medicine and Cell and Developmental Biology at VUMC.
Norton Thoracic Institute is one of the highest volume and best rated lung transplant centers in the nation.
“IPF is one of the most common conditions that causes a patient to need lung transplantation, and it deserves the attention of research,” said Dr. Rajat Walia, section chief of pulmonary medicine and medical director of lung transplantation at Norton Thoracic Institute. Dr. Walia also serves as the facility’s co-investigator for the study, along with Dr. Ross Bremner, executive director of the Institute.
“We are proud to offer our patients the opportunity to be involved in research where they can voluntarily donate tissue samples taken from their scarred lungs at the time of transplant. Our patients know that their gift to science could mean advancements in treatment for future patients,” Dr. Walia added.
Single-cell sequencing will allow the researchers to closely examine the gene expression profiles of individual cells within the lungs in order to identify their function, and ultimately understand the molecular changes that may be driving the disease.
Prior to the advent of single-cell sequencing, researchers could not begin to decipher the molecular source of IPF, Dr. 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.
Dr. Kropski said: “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.”
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 scaring and stiffening in the interstitium.
“Together, both grants will help enable us to closely examine all lung tissues and search for the genomic factors that drive all pulmonary fibrosis,” Dr. 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.”