# Disease Mechanisms of Early Pulmonary Fibrosis

> **NIH NIH P01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $2,857,933

## Abstract

PROGRAM PROJECT SUMMARY
To develop novel, transformative therapies that substantially reduce the burden of morbidity and mortality from
progressive pulmonary fibrosis (PF), a fundamentally new conceptualization of PF is required. It is becoming
clear that lung fibrosis is a consequence, rather than the primary driver, of disease pathobiology and
represents the culmination of a lengthy period of pre-clinical disease progression driven by repetitive cycles of
epithelial injury and dysfunctional repair. Rather than focusing on slowing progression of established PF, we
propose that therapeutic efforts should be directed at preventing the development of symptomatic PF. This
Program will focus primarily on the pre-symptomatic period, which represents the ideal time for interventions to
modify the course of PF. Our overall objective is to re-shape understanding of the natural history of PF by
investigating the transcriptomic, genetic, epigenetic, metabolic, and exposome-related signatures that
contribute to disease initiation and early progression. Our long-term goals are to use the knowledge gained in
this Program to develop new strategies for pre-clinical risk stratification and to identify novel approaches for
disease prevention and treatment. This Program consists of 4 Projects and 3 Cores and will leverage our
ongoing cohort study of asymptomatic relatives of patients with familial PF (FPF). Project 1 titled “Mechanisms
of Early Disease Progression in FPF” will investigate single-cell transcriptomics from blood and
bronchoalveolar lavage cells to identify critical mechanisms driving pre-clinical FPF and develop better
biomarkers for identification of early disease. Project 2 titled “Environmental Exposures in Pre-Clinical FPF” will
use cutting-edge technology combined with standardized assessments to measure real-time exposures and
identify specific environmental toxins that contribute to the early development of PF. Project 3 titled “Functional
genomic mechanisms of epithelial dysfunction in Pulmonary Fibrosis” will utilize single-cell multiomics from
lung biopsies and patient-derived organoid models to investigate the mechanisms through which genetic
factors interact with environmentally-driven stimuli to drive the initiation and progression of PF. Project 4 titled
“Defining the molecular natural history of early and progressive pulmonary fibrosis” will utilize state-of-the-art
spatial transcriptomic technologies and ex vivo culture models to generate a spatially-resolved molecular atlas
of pre-clinical and progressive PF. The Administrative Core houses expertise to manage and support the entire
program, the Clinical and Biospecimen Core will conduct all studies involving human subjects, and the
Genomics Core will support data acquisition, analysis, storage, and dissemination. Together, we anticipate that
the highly-integrated and synergistic nature of this proposal will result in a revolution in understanding of early
PF pathogenesis and facilit...

## Key facts

- **NIH application ID:** 10846182
- **Project number:** 1P01HL172729-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Timothy S. Blackwell
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,857,933
- **Award type:** 1
- **Project period:** 2024-09-17 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846182

## Citation

> US National Institutes of Health, RePORTER application 10846182, Disease Mechanisms of Early Pulmonary Fibrosis (1P01HL172729-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10846182. Licensed CC0.

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