# Local cellular communication networks in COPD endotypes

> **NIH NIH R21** · YALE UNIVERSITY · 2024 · $125,625

## Abstract

PROJECT SUMMARY
Chronic Obstructive Pulmonary Disease (COPD) is an incurable, progressive chronic respiratory disease, and a
leading cause of death in the United States. COPD is a heterogenous syndrome, characterized by diverse clinical
and pathologic manifestations of COPD that vary amongst susceptible individuals. Growing evidence suggests
COPD is characterized by the presence of aberrant cell populations that can be identified using single-cell
sequencing technologies. The overarching goal of this proposal is to provide a deeper understanding of how
these aberrant cells communicate with their microenvironment and identify novel strategies for therapeutic
intervention. Our overarching hypothesis is that COPD heterogeneity is due to aberrant cell-cell and cell-matrix
communication that occur to varying degrees in susceptible individuals. In Aim 1, we will identify aberrant cell-
cell signaling by performing network level analyses of a newly created dataset of single-nuclear RNA sequencing
data generated with frozen lung tissue samples from the Lung Tissue Research Consortium (LTRC). We will
then use spatial transcriptomics from the same samples to provide spatial context to these signaling pathways
and refine our understanding of aberrant cell-cell signaling in COPD. In Aim 2, we will assess cell-matrix
communication networks by performing proteomic profiling of decellularized lung tissue samples from the same
LTRC samples and perform network level analyses to assess cell-matrix interactions that are enriched in disease
or correlate with disease traits. By assessing spatial cell-cell interactions, and aberrant cell-matrix networks, we
hope to identify novel therapeutic targets for COPD.
This proposal is a response to the Funding Opportunity Announcement (FOA) to support meritorious exploratory
research relevant to the NHLBI mission using the existing biospecimen collections that are stored in the NHLBI
Biologic Specimen Repository (Biorepository), thereby maximizing the scientific value of the stored collections,
and providing researchers with an opportunity to generate preliminary data for subsequent research proposals.
Findings from this proposal will be utilized for further mechanistic investigation of potential therapeutic targets.

## Key facts

- **NIH application ID:** 10872670
- **Project number:** 1R21HL173512-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Maor Sauler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $125,625
- **Award type:** 1
- **Project period:** 2024-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872670

## Citation

> US National Institutes of Health, RePORTER application 10872670, Local cellular communication networks in COPD endotypes (1R21HL173512-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10872670. Licensed CC0.

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