# Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $1,489,128

## Abstract

7. Project Summary
The primary objective of this proposal is to characterize the most important genetic and proteomic pathways
that contribute to early stages of pulmonary fibrosis (PF_, with the goal of developing biomarkers for, and
improving our understanding of, the initial biological processes that result in early PF pathogenesis. Idiopathic
pulmonary fibrosis (IPF), the most common and severe form of PF, is increasing in prevalence, and has a
mortality rate worse than most malignancies. Given that even early stages of PF may benefit from interventions
there is more urgency to improve our understanding of early disease detection and to define the most
important pathways that result in early stages of PF progression. In the prior grant cycle, key results helped to
improve our understanding of early progressive PF, demonstrated the key genetic and genomic findings that
overlap, and that are distinct from, IPF, and identified important genomic findings correlated with early stages
of PF. Although these results provide important biologic signals, the predictive power of many of these
biomarkers is low, and they leave important questions unanswered. We hypothesize that comprehensive
proteomic and genetic assessments of ILA will lead to a better understanding of 1) the factors that best help
predict disease risk, 2) the most important pathways implicated in PF development, and 3) which proteins’
secretion is increased in response to higher risk genetic profiles thus implicating their role in early PF
pathogenesis. To address these hypotheses, we propose the following specific aims: Aim 1: Can peripheral
blood proteins be identified that are associated with, and help to predict, early and later stages of progressive
PF? Aim 2: Can polygenic risk scores (PRS) help predict early stage-stage PF and can this genetic data be
integrated with proteomic assessments to improve our understanding of early PF pathogenesis? Aim 3: Can
differentiated human airway epithelial cells (HAECs) demonstrate the role that high genetic risk (and
environmental stimuli) play in the expression of early-stage PF associated proteins? These results will not only
improve our understanding of the pathogenesis of both early and late stage PF, but will also identify candidate
pathways that could lead to targets for drug development, and will identify biomarkers for future interventional
trials designed to target those at the highest risk to develop IPF at a stage before the lung is irrevocably
damaged.

## Key facts

- **NIH application ID:** 10801090
- **Project number:** 2R01HL135142-05A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MICHAEL H. CHO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,489,128
- **Award type:** 2
- **Project period:** 2017-08-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801090

## Citation

> US National Institutes of Health, RePORTER application 10801090, Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities (2R01HL135142-05A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10801090. Licensed CC0.

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