# COPD Susceptibility, Heterogeneity, and Progression:  Proteomics and Genetics

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $898,437

## Abstract

Project Summary/Abstract
Current therapeutic options for chronic obstructive pulmonary disease (COPD) are limited, and new drug
development in COPD has been hampered by the lack of clinically relevant biomarkers to assess likely drug
efficacy. We will identify differentially abundant and lung-specific protein biomarkers of COPD in lung tissue
and blood (plasma) using comprehensive proteomic analysis. Genetic determinants influence COPD
susceptibility, but previously identified COPD genetic determinants account for only a small percentage of
COPD heritability. Genetic analysis of protein biomarkers could reveal the network of regulatory factors
influencing COPD susceptibility and COPD heterogeneity. Our overall hypothesis is that functional genetic
variants lead to abnormal proteomic states that influence the development and heterogeneity of COPD. We
will identify potential COPD biomarkers by studying lung-specific proteins that differ in lung tissue and plasma
from 100 COPD cases and 50 smoking control subjects. We will then measure the most promising lung-
specific plasma proteins in 1950 non-Hispanic White and African American COPDGene subjects with distinct
imaging characteristics (airway-predominant COPD, emphysema-predominant COPD, and resistant smokers)
to identify protein biomarkers associated with COPD and COPD subtypes. We will also perform genetic
association analysis of lung-specific protein levels using whole genome sequencing data in these COPDGene
subjects. Genetic determinants of protein biomarker levels will be tested for association with COPD
susceptibility and COPD subtypes in multiple COPD populations. We will then determine whether the
integrated analysis of the identified protein biomarkers of COPD susceptibility, several previously reported
COPD protein biomarkers (CC16, Surfactant Protein D, sRAGE, and PARC), and the genetic determinants of
COPD and COPD protein biomarkers enables prediction of disease progression rates in mild-to-moderate
COPD subjects. The identification and characterization of novel COPD protein biomarkers may provide
insights into COPD pathogenesis and tools for future clinical trials.

## Key facts

- **NIH application ID:** 9912815
- **Project number:** 5R01HL133135-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Robert L Moritz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $898,437
- **Award type:** 5
- **Project period:** 2017-04-12 → 2022-08-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912815

## Citation

> US National Institutes of Health, RePORTER application 9912815, COPD Susceptibility, Heterogeneity, and Progression:  Proteomics and Genetics (5R01HL133135-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9912815. Licensed CC0.

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