Vanderbilt University Medical Center will collaborate with TGen, part of City of Hope, and the University of Michigan to support innovative research to uncover the molecular drivers of pulmonary diseases with the goal of improving prevention, diagnosis and treatment.
Three collaborative grants, totaling over $22 million, were awarded by the National Institutes of Health’s National Heart, Lung, and Blood Institute and will be led by a team of VUMC investigators including Jonathan Kropski, MD, associate professor of Medicine, and Margaret Salisbury, MD, assistant professor of Medicine, both in the Division of Allergy, Pulmonary and Critical Care Medicine, and Jennifer Sucre, MD, associate professor of Pediatrics, together with Nicholas Banovich, PhD, associate professor and division director of Bioinnovation and Genome Sciences at TGen and Timothy Blackwell, MD, chair of the Department of Internal Medicine at the University of Michigan and former director of the Division of Allergy, Pulmonary and Critical Care Medicine at VUMC.
In addition to co-investigators at VUMC, TGen and Michigan, the investigative team also includes Davis McCarthy, DPhil, head of Bioinformatics and Cellular Genomics at St. Vincent’s Institute of Medical Research.
“The current treatments we have for patients with pulmonary fibrosis at best slow the progression of the disease — none of our treatments halt or reverse the fibrotic process or improve symptoms of quality of life for patients with this disease,” said Kropski, who holds the Rudy W. Jacobson Chair in Pulmonary Medicine. “Our focus in these projects is understanding how this disease begins, with the goal of developing strategies to not just slow the fibrotic process but promote lung maintenance and repair.”
The first grant, titled “Spatiotemporal Genomic Regulation of Disease Initiation and Progression in Pulmonary Fibrosis,” focuses on mid- to late-stage idiopathic pulmonary fibrosis, a chronic lung disease characterized by progressive scarring of lung tissue. This scarring reduces lung function over time, causing symptoms such as shortness of breath, persistent cough and fatigue.
This project applies advanced single-cell RNA sequencing, spatial transcriptomics and multiomic tools to dissect the genetic and molecular mechanisms driving disease progression. These insights will help guide the development of new therapeutic strategies aimed at slowing or halting disease progression in patients.
“Most studies of pulmonary fibrosis have relied on samples collected at the time of lung transplant, which are very advanced in the disease process,” Banovich said. “This study will utilize samples collected during diagnostic lung biopsies to allow us to explore the disease process when patients are first developing symptoms and being diagnosed.”
The second, a program project grant, “Disease Mechanisms of Early Pulmonary Fibrosis,” involves teams from VUMC, TGen and the University of Michigan focusing even earlier in the disease process — long before patients develop symptoms and the early-stage lung abnormalities develop. The study includes four projects led by Blackwell, Salisbury, Kropski and Banovich leveraging a unique cohort of asymptomatic relatives of patients with familial pulmonary fibrosis.
The projects will examine epigenetic aging, environmental exposures, genetic factors and lung tissue multiomics to understand what the earliest molecular changes driving disease are and where they occur.
“By studying this cohort of individuals at increased risk for pulmonary fibrosis, we are uniquely poised to identify modifiable environmental factors and targetable cellular mechanisms that could reduce their chances of developing pulmonary fibrosis in the future,” Salisbury said.
The third grant, “Unraveling the Molecular Origins of Chronic Parenchymal Lung Diseases,” spans the full spectrum of lung disease, from the early childhood condition bronchopulmonary dysplasia to adult pulmonary fibrosis. This grant is part of Phase3 of the LungMap consortium, a multicenter initiative aimed at creating a comprehensive molecular map of the lungs across the lifespan. The project integrates cutting-edge spatial technologies to explore how injury responses in the lung alveolus shape disease progression from childhood to adulthood. By developing high-resolution molecular maps, this work seeks to uncover early intervention points and improve outcomes for patients across different stages of life.
“We increasingly recognize that early-life events shape risk for adult diseases, but it is less clear how different responses to injury impact lung repair across the lifespan,” said Sucre, director of the Biodevelopmental Origins of Lung Disease Center in the Department of Pediatrics.
Banovich said this work builds on the past seven years of collaborations between the Banovich Lab at TGen and the Kropski, Sucre and Blackwell labs at VUMC, and now the University of Michigan.
“Receiving NIH funding is always an honor and very exciting, but what is really special about these grants is the synergy between them,” Banovich said. “While any one of these projects would have been impactful to pursue, what we can learn by integrating across them will give us unprecedented insights into the molecular mechanisms underlying the origins and progression of chronic lung disease.”
