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Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities

Award Number: R01HL135142
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities - 7. Project Summary The primary objective of this proposal is to characterize the most important genetic and proteomic pathways that contribute to early stages of pulmonary fibrosis (PF_, with the goal of developing biomarkers for, and improving our understanding of, the initial biological processes that result in early PF pathogenesis. Idiopathic pulmonary fibrosis (IPF), the most common and severe form of PF, is increasing in prevalence, and has a mortality rate worse than most malignancies. Given that even early stages of PF may benefit from interventions there is more urgency to improve our understanding of early disease detection and to define the most important pathways that result in early stages of PF progression. In the prior grant cycle, key results helped to improve our understanding of early progressive PF, demonstrated the key genetic and genomic findings that overlap, and that are distinct from, IPF, and identified important genomic findings correlated with early stages of PF. Although these results provide important biologic signals, the predictive power of many of these biomarkers is low, and they leave important questions unanswered. We hypothesize that comprehensive proteomic and genetic assessments of ILA will lead to a better understanding of 1) the factors that best help predict disease risk, 2) the most important pathways implicated in PF development, and 3) which proteins’ secretion is increased in response to higher risk genetic profiles thus implicating their role in early PF pathogenesis. To address these hypotheses, we propose the following specific aims: Aim 1: Can peripheral blood proteins be identified that are associated with, and help to predict, early and later stages of progressive PF? Aim 2: Can polygenic risk scores (PRS) help predict early stage-stage PF and can this genetic data be integrated with proteomic assessments to improve our understanding of early PF pathogenesis? Aim 3: Can differentiated human airway epithelial cells (HAECs) demonstrate the role that high genetic risk (and environmental stimuli) play in the expression of early-stage PF associated proteins? These results will not only improve our understanding of the pathogenesis of both early and late stage PF, but will also identify candidate pathways that could lead to targets for drug development, and will identify biomarkers for future interventional trials designed to target those at the highest risk to develop IPF at a stage before the lung is irrevocably damaged.


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 = $1,582,806 )
2026	2026	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	7	4/2/2026	NON-COMPETING CONTINUATION	$1,582,806
														Subtotal = $1,582,806

Issue Date FY: 2025 ( Subtotal = $1,542,983 )
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	003	6	9/22/2025	NON-COMPETING CONTINUATION	$154,297
2025	2025	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	6	11/26/2024	NON-COMPETING CONTINUATION	$1,388,686
2025	2020	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	001	4	1/31/2025	NON-COMPETING CONTINUATION	-$3,981
2025	2020	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	002	4	9/9/2025	NON-COMPETING CONTINUATION	$3,981
														Subtotal = $1,542,983

Issue Date FY: 2024 ( Subtotal = $1,489,128 )
2024	2024	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	5	1/26/2024	COMPETING CONTINUATION	$1,489,128
														Subtotal = $1,489,128

Issue Date FY: 2023 ( Subtotal = -$3,981 )
2023	2020	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	4	7/28/2023	NON-COMPETING CONTINUATION	-$3,981
														Subtotal = -$3,981

Issue Date FY: 2020 ( Subtotal = $800,376 )
2020	2020	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	4	7/16/2020	NON-COMPETING CONTINUATION	$800,376
														Subtotal = $800,376

Issue Date FY: 2019 ( Subtotal = $843,606 )
2019	2019	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	3	7/23/2019	NON-COMPETING CONTINUATION	$843,606
														Subtotal = $843,606

Issue Date FY: 2018 ( Subtotal = $669,110 )
2018	2018	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	2	7/12/2018	NON-COMPETING CONTINUATION	$669,110
														Subtotal = $669,110

Issue Date FY: 2017 ( Subtotal = $787,403 )
2017	2017	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Lung Diseases Research	000	1	6/23/2017	NEW	$787,403
														Subtotal = $787,403

Grand Total All Awards = $7,711,432

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Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities

Award Number: R01HL135142

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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