Researchers at Vanderbilt University Medical Center are leading a multiomic study to identify early drivers of pulmonary fibrosis (PF) in an at-risk patient population. Vanderbilt has a collection of samples from patients and family members they have been following for up-to ten years. They are partnering with Translational Genomics Research Institute (TGen) for this research.
Each year, 40,000-50,000 individuals are diagnosed with PF in the US, and 40,000 lose their lives to the disease. Currently, there are no available therapies for PF. Most patients with pulmonary fibrosis progress to death or lung transplant within 3-5 years of diagnosis.
PF is currently a general term. It can be caused by exposure to asbestos or silica dust, but is also seen in patients with autoimmune diseases such as systemic sclerosis or arthritis. It is known that genetic factors are important in risk of the condition.
“To develop transformative therapies, it is essential to understand what initiates the disease and what drives progression of the disease,” said Jonathan Kropski, MD, assistant professor, department of medicine at Vanderbilt University Medical Center. “To do this, research must focus on the very earliest aspect of the disease – before people develop symptoms and before it can be detected on X-rays or CT scans of the lung.”
Kropski will oversee study operations, analysis, and coordination among the sites along with Nicholas Banovich, PhD, an associate professor at TGen. Banovich, who specializes in human genetics, genomics and single-cell biology, will oversee analysis of lung tissue samples.
The research team will profile biopsy tissue using the 10X Genomics Multiome system (jointly profiling gene expression and chromatin accessibility), and analyze spatial transcriptomics using the Cartana in situ sequencing technology, which was recently acquired by 10X. Because the team’s samples comprise biospecimens from pre-symptomatic individuals, they offer the opportunity to investigate the beginning of early interstitial lung disease.
“These relatives of FPF patients underwent bronchoscopic lung biopsies at the time of study enrollment, and have been followed for the past 5-10 years with repeat CT scans, and we know some of these relatives have gone on to develop pulmonary fibrosis during follow-up,” says Kropski, “By interrogating pre-disease samples from these individuals, we think there is a unique opportunity to examine early disease mechanisms.”
The prospective cohort study was established at Vanderbilt back in 2008. It has enrolled pre-symptomatic individuals at high genetic risk for PF and followed them prospectively for more than a decade. The goal is to identify incident cases of PF and use these biosamples to examine the molecular drivers of disease. TGen is one of a small number of institutions around the world with the capability to perform these state-of-the-art multiomic and spatial transcriptomic studies.
“VUMC and TGen have already collaborated closely on studies using single-cell biology approaches to study advanced disease in patients with pulmonary fibrosis, and this project builds upon that expertise and experience with a focus on the earliest aspects of disease pathogenesis,” said Kropski and Banovich in a joint statement.
Funding for the research is being provided by Three Lakes Foundation, a nonprofit dedicated to serving as a catalyst for uniting research, industries, and philanthropy in pulmonary fibrosis.
“This study expands our work in established disease,” said Cheryl Nickerson-Nutter, PhD, VP of research and development at Three Lakes Foundation. “We believe it will provide critical clues in how PF develops and ultimately lead to discovery of new therapies capable of stopping and reversing disease progression.”
