# Molecular Markers of Idiopathic Pulmonary Fibrosis Progression

> **NIH NIH K23** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $178,195

## Abstract

PROJECT SUMMARY
Idiopathic pulmonary fibrosis (IPF) is a devastating disorder of unknown etiology with a median survival of only
2-3 years. The rate of disease progression for individuals with IPF is highly variable. Rapid progression occurs
in only 20-30% of patients but is responsible for 75% of IPF-related deaths. A major problem facing clinicians is
that they are unable to identify patients that will experience rapid progression until after irreversible lung
function decline occurs. Dr. Newton has previously demonstrated that pathogenic genetic variants in telomere-
maintenance genes predispose to rapid progression; however, these static genetic variants alone do not
explain the extreme heterogeneity in IPF clinical course. The variability in clinical course is strongly influenced
by environmental exposures such as cigarette smoke or inflammation, which can alter chromatin structure and
availability of gene regulatory elements, thus reprogramming gene expression profiles that produce divergent
IPF disease course phenotypes. Therefore, Dr. Newton hypothesizes that integrating chromatin accessibility
with gene expression will allow for the discovery of novel molecular markers and biologically relevant driver
pathways that differentiate IPF disease course phenotypes. Along these lines, his Specific Aims are to 1)
identify IPF patients at high-risk for short-term rapid progression using clinical, genomic, epigenetic, and gene
expression signatures, 2) discover gene regulatory elements and biologic pathways that are associated with
rapid IPF progression, and 3) identify changes in chromatin accessibility and gene expression that correspond
to acute IPF exacerbations. To accomplish these aims, he has established a prospective IPF cohort designed
to perform serial blood collection while simultaneously quantifying the rate of IPF progression. Using RNA and
DNA from blood lymphocytes of IPF patients collected longitudinally as their disease evolves, he will integrate
transcriptome patterns with chromatin features to identify biologic pathways in easily accessible blood cells that
signify high-risk IPF. The data generated from these aims will form the foundation for two subsequent
independent proposals that will seek to validate a blood-based molecular profile that identifies IPF patients at
high-risk for rapid progression, and explore and biologically validate the influence epigenetic regulation on
gene expression patterns and driver pathways within the context of IPF disease course. Dr. Newton has a
sustained track record of high-impact translational research using genetic and genomic markers to predict
clinical outcomes in pulmonary fibrosis. This K23 will allow him to obtain the necessary training to expand his
technical skills and expertise in developing and validating novel biomarkers, constructing clinically useful
prediction models, and integrating next-generation sequencing technologies. His mentoring team is composed
of highly accomplished sc...

## Key facts

- **NIH application ID:** 10847346
- **Project number:** 5K23HL148498-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Chad Alan Newton
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $178,195
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847346

## Citation

> US National Institutes of Health, RePORTER application 10847346, Molecular Markers of Idiopathic Pulmonary Fibrosis Progression (5K23HL148498-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10847346. Licensed CC0.

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