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Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis

Award Number: R01HL148437
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis - PROJECT SUMMARY/ABSTRACT: Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease, resulting from inhalational exposure to a large variety of antigens. For unknown reasons, a subgroup of patients with HP without a known inciting antigen exposure develops chronic disease with progressive pulmonary fibrosis (the leading cause of death). Accurately identifying patients at risk of disease progression is necessary for prognosis and therapy. The objective of this proposal is to refine our current clinical risk stratification by identifying and validating a transcriptomic signature from peripheral blood mononuclear cells in patients with chronic HP that is predictive of disease progression. We hypothesize that the clinical course of chronic HP is associated with a peripheral blood gene expression signature of risk that can be used to refine the prognosis and predict the clinical outcome. Guided by strong preliminary data, this hypothesis will be tested by two specific aims: i) Establish transcriptomic signatures at time of initial presentation in peripheral blood mononuclear cells from patients with chronic HP in a Discovery cohort and then validate the signature in an independent chronic HP replication cohort; and ii) Establish a time-course transcriptomic profile predictive of disease progression in the Discovery cohort and validate the signature profile in the independent chronic HP replication cohort. pursuing The proposed research is significant because it will provide the knowledge that will enhance our ability to predict disease progression, a level of prognostication which is not possible with current clinical measures alone. Relevance to Public Health: This is an important and under-investigated area that has the potential to fundamentally advance our understanding of the pathobiology of disease progression and provide the groundwork to define molecular targets relevant to chronic HP disease progression.


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: 2026 ( Subtotal = $0 )
2026	2023	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	4	12/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	4	7/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	001	4	9/26/2024	NON-COMPETING CONTINUATION	$0
2024	2023	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	4	9/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $579,069 )
2023	2023	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	4	6/30/2023	NON-COMPETING CONTINUATION	$579,069
														Subtotal = $579,069

Issue Date FY: 2022 ( Subtotal = $342,944 )
2022	2022	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	3	8/22/2022	NON-COMPETING CONTINUATION	$342,944
														Subtotal = $342,944

Issue Date FY: 2021 ( Subtotal = $728,047 )
2021	2021	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	2	7/21/2021	NON-COMPETING CONTINUATION	$728,047
														Subtotal = $728,047

Issue Date FY: 2020 ( Subtotal = $862,236 )
2020	2020	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	000	1	7/27/2020	NEW	$862,236
2020	2020	NATIONAL JEWISH HEALTH	1400 JACKSON ST	DENVER	CO	80206	DENVER	USA	Lung Diseases Research	001	1	9/5/2020	NEW	$0
														Subtotal = $862,236

Grand Total All Awards = $2,512,296

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Development and Validation of a Prognostic Transcriptomic Signature for Chronic Hypersensitivity Pneumonitis

Award Number: R01HL148437

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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