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Epithelial innate signaling in airway inflammation and remodeling

Award Number: P01AI062885
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2004
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Epithelial innate signaling in airway inflammation and remodeling - Respiratory Syncytial Virus (RSV) is a leading cause of childhood respiratory disease, responsible for 75,000– 125,000 hospitalizations annually and producing significant morbidity and economic impact. No vaccine is currently licensed to prevent RSV infections. Children hospitalized for RSV lower respiratory tract infections (LRTIs) have reduced pulmonary function, a significant predictor of adult chronic lung disease. This is a competing renewal for our P01, originally funded as AADCRC AI46004 and subsequently through two P01 cycles (9/1/2005-present). Work in our P01 has elucidated mechanisms by which RSV infection produces a rapid epithelial oxidative stress response, triggering innate signaling and resulting in cytokine secretion that triggers and shapes adaptive immunity. More recently, we have developed additional compelling evidence supporting the central theme of this P01 – that innate inflammation produced by infection with the ubiquitous viral pathogen RSV impairs antioxidant capacity, producing disease and triggering long-term airway remodeling. Our projects are developed from original discoveries by our internationally recognized project leaders (PLs) expert in innate inflammation, oxidative stress, and the DNA damage response. Our renewal includes three major research projects (RPs): 1) RP1 (“Epigenetic regulation of innate inflammation-driven airway remodeling”) will focus on the role of the NFκB-coactivator, a chromatin remodeling complex (CRC) nucleated by bromodomain-containing protein 4 (BRD4) in RSV-induced remodeling via epithelial- mesenchymal transition and myofibroblast expansion; 2) RP2 (“The role of innate immunity in downregulation of the airway antioxidant response during paramyxovirus infection”) will focus on how RSV causes disease mediated by unbalanced ROS production via a progressive decrease in NF-E2-related factor 2 (NRF2); and 3) RP3 (“Linkage of the oxidant induced OGG1-DNA complex to airway inflammation and remodeling”) will test the hypothesis that RSV-induced epigenetic modification via oxidation of guanine to oxoG in gene regulatory regions controls acute/chronic inflammation and airway remodeling via the NFκB pathway. This P01 is guided by regular and sustained interactions with our Internal and External Advisory Committees and is nurtured by significant institutional support from UTMB Centers, Departments, and Institutes. All our inter-related and synergistic RPs are supported by an Administrative Core, and human subjects and viral preparations from the Infant Bronchiolitis and Viral Core (IBVC). Translational advances include applications of BRD4 inhibitors, NRF2 agonists, and OGG1 inhibitors that in preclinical studies show promise to interfere with RSV-induced inflammation and remodeling. Upon completion, this P01 will have identified mechanisms of innate signaling-induced remodeling and developed strategies for reversing remodeling and restoring defective innate immunity in allergic airway diseases.


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 = -$222 )
2026	2022	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	15	12/19/2025	NON-COMPETING CONTINUATION	-$222
														Subtotal = -$222

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	15	7/2/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,754,487 )
2022	2022	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	001	15	6/29/2022	NON-COMPETING CONTINUATION	$1,754,585
2022	2016	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	10	10/1/2021	EXTENSION WITH OR WITHOUT FUNDS	-$98
														Subtotal = $1,754,487

Issue Date FY: 2021 ( Subtotal = $1,754,585 )
2021	2021	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	14	7/14/2021	NON-COMPETING CONTINUATION	$1,754,585
														Subtotal = $1,754,585

Issue Date FY: 2020 ( Subtotal = $1,754,585 )
2020	2020	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	13	6/30/2020	NON-COMPETING CONTINUATION	$1,754,585
														Subtotal = $1,754,585

Issue Date FY: 2019 ( Subtotal = $2,149,585 )
2019	2019	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	002	12	7/8/2019	NON-COMPETING CONTINUATION	$1,754,585
2019	2019	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	003	12	7/22/2019	NON-COMPETING CONTINUATION	$395,000
2019	2018	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	001	11	4/22/2019	COMPETING CONTINUATION	$17,593
2019	2016	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	10	4/22/2019	EXTENSION WITH OR WITHOUT FUNDS	-$17,593
														Subtotal = $2,149,585

Issue Date FY: 2018 ( Subtotal = $1,767,677 )
2018	2018	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	001	11	7/24/2018	COMPETING CONTINUATION	$1,767,677
2018	2016	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	10	7/24/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $1,767,677

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	001	10	2/27/2017	EXTENSION WITH OR WITHOUT FUNDS	$381,323
2017	2015	UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON	301 UNIVERSITY BLVD	GALVESTON	TX	77555	GALVESTON	USA	Allergy and Infectious Diseases Research	000	9	2/27/2017	NON-COMPETING CONTINUATION	-$381,323
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $1,528,891 )
2016	2016	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	10	8/5/2016	EXTENSION WITH OR WITHOUT FUNDS	$1,528,891
														Subtotal = $1,528,891

Issue Date FY: 2015 ( Subtotal = $1,528,893 )
2015	2015	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	9	7/30/2015	NON-COMPETING CONTINUATION	$1,528,893
														Subtotal = $1,528,893

Issue Date FY: 2014 ( Subtotal = $1,528,891 )
2014	2014	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	8	7/31/2014	NON-COMPETING CONTINUATION	$1,528,891
														Subtotal = $1,528,891

Issue Date FY: 2013 ( Subtotal = $1,426,621 )
2013	2013	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	7	8/6/2013	NON-COMPETING CONTINUATION	$1,426,621
														Subtotal = $1,426,621

Issue Date FY: 2012 ( Subtotal = $1,523,273 )
2012	2012	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	6	8/21/2012	COMPETING CONTINUATION	$1,523,273
														Subtotal = $1,523,273

Issue Date FY: 2011 ( Subtotal = $0 )
2011	2010	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	001	5	4/14/2011	SUPPLEMENT FOR EXPANSION	$0
2011	2009	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	5	4/14/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $1,213,096 )
2010	2010	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	5	2/2/2010	SUPPLEMENT FOR EXPANSION	$1,213,096
														Subtotal = $1,213,096

Issue Date FY: 2009 ( Subtotal = $1,275,174 )
2009	2009	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	5	4/14/2009	NON-COMPETING CONTINUATION	$1,275,174
														Subtotal = $1,275,174

Issue Date FY: 2008 ( Subtotal = $1,238,099 )
2008	2008	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	4	3/31/2008	NON-COMPETING CONTINUATION	$1,238,099
														Subtotal = $1,238,099

Issue Date FY: 2007 ( Subtotal = $1,249,085 )
2007	2007	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	3	3/30/2007	NON-COMPETING CONTINUATION	$1,249,085
														Subtotal = $1,249,085

Issue Date FY: 2006 ( Subtotal = $1,225,301 )
2006	2006	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	2	5/12/2006	NON-COMPETING CONTINUATION	$1,225,301
														Subtotal = $1,225,301

Issue Date FY: 2005 ( Subtotal = $1,011,624 )
2005	2005	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Allergy and Infectious Diseases Research	000	1	6/30/2005	NEW	$1,011,624
														Subtotal = $1,011,624

Grand Total All Awards = $23,929,644

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Epithelial innate signaling in airway inflammation and remodeling

Award Number: P01AI062885

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2004

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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