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Nevada IDeA Networks of Biomedical Research Excellence (INBRE) Women's Health Administrative Supplement

Award Number: P20GM103440
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY ABSTRACT Preterm Birth (PTB) is a global problem and preemies are at risk for major disability. At the present time, 10-14% of US births are premature depending on maternal ethnicity. African Americans are disproportionally affected; a recognized health disparity. The regulation of birth timing is unknown and PTB cannot be prevented. Tocolytics currently employed have unwanted effects on mother and fetus limiting dosing and none are FDA approved. Tocolytic approaches to prevent PTB must be based on myometrial relaxation mechanisms known to be unique. This is an urgent and unmet need exacerbated because the regulation of uterine smooth muscle relaxation is disparate from that of other smooth muscles. Activation of cAMP-protein kinase (PKA) by the β2 agonist terbutaline, or blockade of calcium entry by nifedipine is unable to provide meaningful tocolysis, and while nitric oxide relaxes term myometrium, it does so in a cGMP- independent manner. Moreover, nitric oxide-mediated relaxation is blunted in spontaneous preterm labor, a dysfunction correlated with over-expression of S-nitrosoglutathione reductase. There is an unmet need to identify the pathways driving quiescence during human gestation to develop new effective tocolytics. Our central hypothesis is that Pezo1 stretch-activated channels exist in both the microvascular endothelium and the uterine smooth muscle and both receptor pools coordinate gestational relaxation via stretch. Piezo1- mediated nitric oxide generation in the endothelial cell compartment S-nitrosates the K+ channel TREK-1 in the myocyte compartment. A Piezo1 agonist together with blockade of nitric oxide metabolism by inhibition of S- nitrosoglutathione reductase to promote nitrosation, together with small molecule activation of TREK-1 will result in additive potassium efflux that will reverse the dysfunctional relaxation of preterm tissues to NO donors. This supplement project is proposed under the Nevada INBRE grant P20GM103440. The goal of the Nevada INBRE is to enhance biomedical research infrastructure, research competitiveness, training and workforce development throughout the state of Nevada. The specific focus area of the INBRE is growth and differentiation. As a participating NIH IC, the NICHD seeks to fund the development of novel and effective pharmacotherapeutic strategies to improve clinical outcomes for women and mothers. The goals of the Nevada INBRE and the NICHD come together in the setting of fetal development in utero interrupted by spontaneous preterm labor leading to preterm birth of an underdeveloped fetus. The research project described in this application is part of the development of a future NIH COBRE Center program in women’s reproductive health research supported by the Core services of the INBRE at the University of Nevada School of Medicine. Successfully exploring the research described in this supplement request will provide data to support a full NIH R01 application to provide preclinical evidence of effective combination tocolysis.


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: 2024 ( Subtotal = $4,515,055 )
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	003	22	9/11/2024	SUPPLEMENT FOR EXPANSION	$265,492
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	22	4/8/2024	SUPPLEMENT FOR EXPANSION	$353,889
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	22	4/3/2024	NON-COMPETING CONTINUATION	$3,506,108
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	002	22	6/5/2024	NON-COMPETING CONTINUATION	$389,566
														Subtotal = $4,515,055

Issue Date FY: 2023 ( Subtotal = $4,078,174 )
2023	2023	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	21	4/13/2023	SUPPLEMENT FOR EXPANSION	$182,500
2023	2023	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	003	21	9/21/2023	NON-COMPETING CONTINUATION	$0
2023	2023	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	002	21	9/1/2023	NON-COMPETING CONTINUATION	$0
2023	2023	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	21	4/12/2023	NON-COMPETING CONTINUATION	$3,895,674
														Subtotal = $4,078,174

Issue Date FY: 2022 ( Subtotal = $4,566,683 )
2022	2022	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	007	20	6/28/2022	NON-COMPETING CONTINUATION	$0
2022	2022	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	005	20	5/13/2022	SUPPLEMENT FOR EXPANSION	$123,509
2022	2022	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	006	20	5/20/2022	NON-COMPETING CONTINUATION	$389,571
2022	2022	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	008	20	7/9/2022	SUPPLEMENT FOR EXPANSION	$547,500
2022	2022	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	004	20	4/1/2022	NON-COMPETING CONTINUATION	$3,506,103
2022	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	003	19	2/17/2022	COMPETING CONTINUATION	$856,967
2022	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	18	11/17/2021	SUPPLEMENT FOR EXPANSION	$0
2022	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	18	2/17/2022	NON-COMPETING CONTINUATION	-$713,467
2022	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	002	18	2/17/2022	SUPPLEMENT FOR EXPANSION	-$143,500
														Subtotal = $4,566,683

Issue Date FY: 2021 ( Subtotal = $4,933,545 )
2021	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	003	19	7/12/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	004	19	7/29/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	002	19	6/28/2021	SUPPLEMENT FOR EXPANSION	$720,000
2021	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	19	6/1/2021	COMPETING CONTINUATION	$4,213,545
2021	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	18	5/31/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $4,933,545

Issue Date FY: 2020 ( Subtotal = $3,617,089 )
2020	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	18	5/22/2020	NON-COMPETING CONTINUATION	$3,473,589
2020	2020	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	18	8/24/2020	SUPPLEMENT FOR EXPANSION	$143,500
														Subtotal = $3,617,089

Issue Date FY: 2019 ( Subtotal = $3,473,589 )
2019	2019	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	17	4/26/2019	NON-COMPETING CONTINUATION	$3,473,589
2019	2019	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	17	8/5/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,473,589

Issue Date FY: 2018 ( Subtotal = $3,473,589 )
2018	2018	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	16	5/14/2018	NON-COMPETING CONTINUATION	$347,358
2018	2018	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	16	3/28/2018	NON-COMPETING CONTINUATION	$3,126,231
														Subtotal = $3,473,589

Issue Date FY: 2017 ( Subtotal = $3,473,589 )
2017	2017	UNIVERSITY OF NEVADA, RENO	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	15	6/20/2017	NON-COMPETING CONTINUATION	$347,358
2017	2017	UNIVERSITY OF NEVADA, RENO	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	15	3/15/2017	NON-COMPETING CONTINUATION	$3,126,231
														Subtotal = $3,473,589

Issue Date FY: 2016 ( Subtotal = $4,032,520 )
2016	2016	UNIVERSITY OF NEVADA-RENO	**	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	001	14	3/28/2016	COMPETING CONTINUATION	$3,647,077
2016	2016	UNIVERSITY OF NEVADA-RENO	**	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	002	14	8/15/2016	SUPPLEMENT FOR EXPANSION	$385,443
2016	2014	UNIVERSITY OF NEVADA-RENO	**	RENO	NV	895570025	WASHOE	USA	Biomedical Research and Research Training	000	13	3/27/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $4,032,520

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2014	UNIVERSITY OF NEVADA-RENO	**	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	13	1/16/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $2,690,816 )
2014	2014	UNIVERSITY OF NEVADA-RENO	**	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	13	6/16/2014	NON-COMPETING CONTINUATION	$2,690,816
														Subtotal = $2,690,816

Issue Date FY: 2013 ( Subtotal = $2,649,419 )
2013	2013	UNIVERSITY OF NEVADA-RENO	204 Ross Hall Mailstop 325	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	12	7/16/2013	NON-COMPETING CONTINUATION	$2,649,419
														Subtotal = $2,649,419

Issue Date FY: 2012 ( Subtotal = $2,805,994 ) (Continued on the next page)
2012	2012	UNIVERSITY OF NEVADA-RENO	204 Ross Hall Mailstop 325	RENO	NV	89557	WASHOE	USA	Biomedical Research and Research Training	000	11	6/6/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$2,805,994
Grand Total All Awards = $44,310,062

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Nevada IDeA Networks of Biomedical Research Excellence (INBRE) Women's Health Administrative Supplement

Award Number: P20GM103440

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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