# Leveraging Variant-perturbed Gene Regulation to Support Precision Medicine in COPD

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $815,645

## Abstract

Summary/Abstract
 Micro-ribonucleic acids (miRNAs) are crucial for normal lung development, lung health, and have been
implicated in lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). In addition, recent
studies have identified miRNAs as potential therapeutic targets for COPD. miRNAs play an important role in
gene regulation. miRNAs act within a complex regulatory structure that involves other biological molecules,
including transcription factors, proteins, messenger RNAs (mRNAs), and other epigenetic mechanisms, all of
which may be under the influence of genetic variants. A number of genetic variants have been identified as
important for COPD through Genome-Wide Association Studies (GWAS). However, substantial computational
and methodological challenges impede both linking genetic variants to altered molecular mechanisms and
identifying therapeutic interventions that can effectively target these mechanisms for clinical impact.
Understanding the complex structure of gene regulation, including by and of miRNAs, and how it is altered in
disease or in response to a genetic variant, is critical for developing effective, precision-medicine based
therapeutic strategies in COPD.
 In this project, we hypothesize that network-based methods, which model the collective response of biological
molecules, have the potential to identify novel therapeutic strategies for COPD. Our goal is to leverage the
predictions made by regulatory network models in a Connectivity Map analysis to identify potential therapeutic
interventions for COPD. To accomplish this goal, we will first develop a network approach to model regulation
by and of miRNAs using existing mRNA and miRNA expression data from blood samples in COPDGene. We
will also generate miRNA expression data in lung tissue from the Lung Tissue Research Consortium (LTRC).
We will use these data to assess changes in miRNAs related to COPD and to quantify associations between
miRNAs and genetic variants. Co-expression, regulatory, and genetic-association networks will be developed to
support multi-Omics predictions relevant to COPD. Network analysis results will be analyzed in the context of
drug response profiles from the Connectivity Map to identify potential treatment strategies. The outcome of this
project will be a deeper understanding of the regulatory role of miRNAs in COPD, how disease-specific miRNA
regulation is altered in the context of COPD GWAS variants, and predictions for novel therapeutic strategies for
COPD. The methods developed in the project will also support the broader goal of developing precision-medicine
strategies for COPD.

## Key facts

- **NIH application ID:** 10365114
- **Project number:** 1R01HL155749-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Kimberly Renee Glass
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $815,645
- **Award type:** 1
- **Project period:** 2022-03-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10365114

## Citation

> US National Institutes of Health, RePORTER application 10365114, Leveraging Variant-perturbed Gene Regulation to Support Precision Medicine in COPD (1R01HL155749-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10365114. Licensed CC0.

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