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Local cellular communication networks in COPD endotypes

Award Number: R21HL173512
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Local cellular communication networks in COPD endotypes - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $125,625 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Lung Diseases Research	001	2	3/24/2025	NON-COMPETING CONTINUATION	$125,625
2025	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Lung Diseases Research	000	1	3/19/2025	NEW	$0
														Subtotal = $125,625

Issue Date FY: 2024 ( Subtotal = $125,625 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Lung Diseases Research	000	1	4/5/2024	NEW	$125,625
														Subtotal = $125,625

Grand Total All Awards = $251,250

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Local cellular communication networks in COPD endotypes

Award Number: R21HL173512

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/15/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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