# Integrating Omics, Networks, and Functional Studies in COPD and IPF

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $379,824

## Abstract

PROJECT SUMMARY
The variable development of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis
(IPF) among smokers could relate to genetic variants, epigenetic determinants, environmental factors, or their
interactions. Rather than operating in isolation, genetic and epigenetic determinants of COPD and IPF likely
influence molecular networks of interacting genes and proteins. Based on progress in murine and human studies
in the first cycle of this PPG, we will focus on mitochondrial and chitinase pathways as potential molecular
switches that impact whether individuals develop COPD or IPF. We hypothesize that a molecular network of
genetic and epigenetic determinants regulating mitochondrial and chitinase proteins confers differential
susceptibility of smokers to develop COPD or IPF. In addition, we hypothesize that mitochondrial and chitinase
pathways influence the heterogeneous manifestations of COPD and IPF. In order to investigate the differential
susceptibility to develop COPD and IPF and the impact of these pathways on COPD and IPF subtypes, we will
leverage our human population-based and genetic/epigenetic resources in COPD and IPF, including the Lung
Tissue Research Consortium (LTRC) and multiple replication populations. We will measure a panel of chitinase
and mitochondrial pathway proteins in plasma and lung biospecimens and test for their association with COPD
and IPF and their related phenotypes. We will identify genetic variants, mitochondrial characteristics, and DNA
methylation marks that influence expression of chitinase and mitochondrial pathway proteins in lung and blood
samples and determine whether these variants are also associated with COPD and/or IPF. We will identify
network relationships within and between the mitochondrial and chitinase pathways by using correlation-based
networks, gene regulatory networks, and protein-protein interaction networks. Key network relationships within
and between mitochondrial and chitinase pathways will be validated using CRISPR-based functional approaches
in lung epithelial cells, monocyte-macrophages, and fibroblasts with readouts of cell death, fibrosis, chitosome
components, mitochondrial function, and inflammation to identify shared and divergent network determinants of
IPF and COPD.

## Key facts

- **NIH application ID:** 10172314
- **Project number:** 2P01HL114501-06A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Edwin K Silverman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,824
- **Award type:** 2
- **Project period:** 2013-09-06 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10172314

## Citation

> US National Institutes of Health, RePORTER application 10172314, Integrating Omics, Networks, and Functional Studies in COPD and IPF (2P01HL114501-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10172314. Licensed CC0.

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