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Genetics of Male Infertility: Accelerating the pace of discovery

Award Number: P50HD096723
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Genetics of Male Infertility: Accelerating the pace of discovery - Abstract: Overall Azoospermia impacts 1% of men globally, which translates to 645,000 men between the ages of 20 and 50 in the United States. It is estimated that genetic causes explain 50% of infertility. Improved knowledge about the genetic basis of infertility and associated overall health comorbidities will aid in the counseling of infertile couples; justify the development of diagnostic screens; and may lead to patient-specific treatment options. In the current personalized medicine era with reduced cost whole genome sequencing and facile genome editing technologies, it is feasible to discover genetic underpinnings of infertility and develop targeted therapies. Project 1 will discover genetic variants in men with unexplained nonobstructive azoospermia (NOA) to identify targets for development of clinical diagnostics or therapy. In addition, Project 1 assemble an international team of experts to develop criteria for review and interpretation of infertility- associated variants to be included in ClinGen, which will facilitate inclusion in clinical diagnostic screens. Project 2 will establish high throughput in vitro gametogenesis platforms and a 100% chimeric mouse strategy for rapid validation of azoospermia-associated variants discovered in Project 1. Project 2 will also evaluate the impact of epigenetic modifiers on primordial germ cell development. Project 3 will provide “gold standard” reproductive phenotyping in mouse models with human NOA associated variants discovered in Project 1 and validated in Project 2. In mouse models of NOA, Project 3 will test the safety and feasibility of Sertoli cell and germ cell gene therapies. Results of all interlinked projects will help justify the use of whole genome sequencing as a diagnostic screen for male infertility and inform the public dialogue on the risks and benefits of gene therapy in and around the germline. Core A will provide administrative oversight and facilitate communications and data exchange among projects and cores to ensure that this P50 program achieves an impact that is greater than the sum of its parts. The Education-Outreach Core will maximize the public impact of this P50 by developing Saturday Academy hands-on laboratory experiences in reproduction and genetics for middle school and high school students in underserved communities in Pittsburgh, Portland and Ithaca. P50 trainees from all sites will also contribute teaching modules to The DataJam, a national nonprofit that runs academic education programs and competitions to engage middle school, high school and community college students in data analytics and critical thinking.


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 = $0 )
2025	2024	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3240 CRAFT PL STE 100	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	6	11/19/2024	COMPETING CONTINUATION	$0
2025	2024	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3240 CRAFT PL STE 100	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	002	6	3/17/2025	COMPETING CONTINUATION	$45,665
2025	2023	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3240 CRAFT PL STE 100	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	001	5	3/17/2025	NON-COMPETING CONTINUATION	-$45,665
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,711,713 )
2024	2024	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3240 CRAFT PL STE 100	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	001	6	9/18/2024	COMPETING CONTINUATION	$1,711,713
2024	2023	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3240 CRAFT PL STE 100	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	5	9/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,711,713

Issue Date FY: 2023 ( Subtotal = $1,623,838 )
2023	2023	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	002	5	3/24/2023	NON-COMPETING CONTINUATION	$1,623,838
2023	2023	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	003	5	5/17/2023	NON-COMPETING CONTINUATION	$0
2023	2022	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	001	4	12/16/2022	NON-COMPETING CONTINUATION	$0
2023	2022	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	4	11/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,623,838

Issue Date FY: 2022 ( Subtotal = $1,641,405 )
2022	2022	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	001	4	4/27/2022	NON-COMPETING CONTINUATION	$0
2022	2022	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	4	4/23/2022	NON-COMPETING CONTINUATION	$1,641,405
														Subtotal = $1,641,405

Issue Date FY: 2021 ( Subtotal = $1,658,528 )
2021	2021	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	3	3/29/2021	NON-COMPETING CONTINUATION	$1,658,528
														Subtotal = $1,658,528

Issue Date FY: 2020 ( Subtotal = $1,676,219 )
2020	2020	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	002	2	7/2/2020	NON-COMPETING CONTINUATION	$0
2020	2020	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	001	2	6/29/2020	NON-COMPETING CONTINUATION	$0
2020	2020	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	2	4/2/2020	NON-COMPETING CONTINUATION	$1,676,219
														Subtotal = $1,676,219

Issue Date FY: 2019 ( Subtotal = $1,819,106 )
2019	2019	MAGEE-WOMENS RESEARCH INSTITUTE AND FOUNDATION	3339 WARD ST	PITTSBURGH	PA	15213	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	1	8/30/2019	NEW	$1,819,106
														Subtotal = $1,819,106

Grand Total All Awards = $10,130,809

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Genetics of Male Infertility: Accelerating the pace of discovery

Award Number: P50HD096723

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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