# Elucidating the genomic determinants of outcomes in idiopathic pulmonary fibrosis

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $79,244

## Abstract

PROJECT SUMMARY/ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a rare, but devastating interstitial lung disease characterized by a
progressive decline in lung function and a median survival of 3-5 years after diagnosis. Despite the poor
prognosis, IPF follows a highly variable clinical course, whereby most patients experience gradual disease
progression, some demonstrate relative stability and a small group dies from rapidly progressive disease. Anti-
fibrotic therapies were recently approved for the treatment of IPF, but it remains unclear which IPF phenotypes
derive the most benefit. Recent advances in genomic technology provide an excellent opportunity to improve
our understanding of IPF progression and treatment response. In this proposal, I aim to take advantage of
these genomic advances to identify single nucleotide polymorphisms (SNPs) linked to relevant IPF outcomes. I
will do this using DNA samples collected from patients enrolled in past and current IPF clinical trials, along with
two large IPF registries. My central hypothesis is that patients genetically predisposed to death, disease
progression and treatment response can be prospectively identified using SNPs linked to these endpoints. I will
first conduct a genome-wide survival analysis to identify SNPs linked to early IPF mortality. I will then genotype
relevant susceptibility and outcome-associated SNPs in several clinical trial datasets to determine whether
they predict relevant trial endpoints, including pulmonary function decline and hospitalization. Finally, I will
genotype SNPs at potential pharmacogenetic loci to determine whether such SNPs modulate the response to
anti-fibrotic therapy. Successful completion of this proposal will lead to the development of customized SNP
chips that inform the design of IPF clinical trials and has a high potential to identify novel genes that may one
day serve as therapeutic targets.
My long-term career goal is to incorporate genetics into clinical decision-making in patients with IPF,
specifically clinical trial enrollment and therapeutic selection. To make progress towards this goal, the relevant
genetic markers with which to stratify IPF cohorts for risk-stratification and pharmacogenetic testing must first
be identified. To do this, a career development has been devised that will provide outstanding mentorship,
hands-on laboratory experience and additional training in genetic epidemiology, statistical genetics and
bioinformatics. I will draw mentorship from leaders in the field of genomics, interstitial lung disease and clinical
and translational investigation. An advisory committee composed of individuals with diverse backgrounds has
been assembled to provide specific guidance with regard to clinical registry and biorepository management,
laboratory training, statistical genetics and outcomes modeling. This K23 award is vital to successful
completion of this proposal and timely execution of my career development plan, as it will provi...

## Key facts

- **NIH application ID:** 10238126
- **Project number:** 5K23HL138190-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Justin M Oldham
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,244
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238126

## Citation

> US National Institutes of Health, RePORTER application 10238126, Elucidating the genomic determinants of outcomes in idiopathic pulmonary fibrosis (5K23HL138190-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10238126. Licensed CC0.

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