Integrated Molecular Pathogenesis of Pulmonary Fibrosis
Abstract
Pulmonary fibrosis (PF) is a heterogeneous clinical syndrome that represents the end-stage of chronic interstitial lung diseases. Dozens of different occupational, environmental, immune and genetic risk factors have been associated with PF, and through the past several decades, risk factor exposures have been the driving force in the diagnostic classification of PF, thus in the current paradigm, there are dozens of different diagnoses of pulmonary fibrosis. This emphasis on distinction has focused much attention on the most common form of this syndrome (Idiopathic Pulmonary Fibrosis, IPF), which comprises only 20% of PF patients. Today there are 2 modestly effective FDA-approved treatments for IPF; however, for the 80% of PF patients with other diagnoses, there are no known effective treatments. The current paradigm emphasizing diagnostic distinction has limited progress in understanding how different risk factors lead to a common end-stage lung pathology. In order to rapidly accelerate progress towards better treatments for all PF patients, a radical departure from this approach is needed. We believe any subdividing of PF should be driven by demonstrated relevant differences in disease biology; to this end, it has become clear that a more nuanced understanding of upstream disease mechanism of disease initiation and propagation, as well as the convergent downstream mechanisms of lung fibrosis is critical. By leveraging the inherent heterogeneity of disease state in the PF lung, we will employ innovative single-cell genomic approaches in particular single cell RNA-seq (scRNA-seq) and culture models to recreate the molecular natural history of disease, determine the convergent mediators and pathways that drive PF pathogenesis and identify mechanistically-driven disease endotypes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2023
- Accession Number
- AD1222279
Entities
People
- Jonathan Andrew Kropski
- Nicholas E Banovich
Organizations
- Translational Genomics Research Institute