Monday, June 23, 2025 6/23/2025

Characterization and prevention of Chemotherapy-Induced Damage to Ovarian Reserve

Award Number: R01HD053112
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: 09/15/2007
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Characterization and prevention of Chemotherapy-Induced Damage to Ovarian Reserve - Abstract: Cancer therapy-induced ovarian insufficiency is a major public health problem affecting millions of women over their reproductive life span. Our overarching aim is to understand and prevent the damage caused by cancer treatments and to extend that knowledge to prevent ovarian aging. In the prior period, we successfully achieved all specific aims and showed: i) Breast cancer chemotherapy but not tamoxifen alone induces a significant decline of ovarian reserve; ii) Women with BRCA mutations have fewer primordial follicles in their ovaries, which accumulate more DNA damage with age compared to controls, and, iii) they experience greater ovarian reserve loss after chemotherapy; iv) Selective knock-down of BRCA1 renders oocytes more liable to chemotherapy-induced death; v) Gonadotoxic chemotherapy causes primordial follicle death by inducing DNA double strand breaks (DSBs), which prompts apoptotic follicle death in primordial follicles but not by activation of their growth in the acute phase. In addition, vi) A ceramide-induced death pathway inhibitor Sphingosine-1- Phosphate (S1P) prevents chemotherapy-induced human ovarian follicle death, likely by enhancing the ATM- Pathway. Given the shared mechanisms through DNA damage and repair, these findings opened new avenues in the prevention of chemotherapy-induced damage to gonadal function, and, to reverse, retard or prevent reproductive aging. In the current renewal, we aim to further these studies with the following translational aims: 1. To determine whether the mutations in BRCA1 vs. BRCA2 or other key members of the ATM-mediated DNA DSB Repair Pathway result in the increased susceptibility to chemotherapy-induced ovarian reserve loss and oocyte death in women with breast cancer; 2. To determine differences in the molecular mechanisms of acute and delayed chemotherapy-induced human primordial follicle loss; 3. To test the efficacy and mechanism of an FDA-approved S1P analogue, FTY-720, in the prevention of chemotherapy-induced human ovarian reserve loss. To achieve these translational aims we will combine clinical studies with studies of basic, translational mechanisms using in vivo human ovarian xenograft models, laser-captured individual-oocyte RNA sequencing and single-cell quantitative real-time PCR approaches which evolved in our laboratory during the past funding periods. These translational studies with human material will be mechanistically strengthened with an in vitro mouse oocyte gene-interference and genotoxicity assay (GTA), which we also developed and validated in the past funding periods. This translational proposal will not only expand knowledge of the mechanisms and prevention of chemotherapy- induced ovarian damage but also result in a paradigm shift in our understanding of how ovarian germ cells mitigate genotoxic stress in general. The exploitation of such mechanisms, in addition to leading to new fertility preservation strategies, will provide new insights into future discoveries to moderate reproductive, and potentially, somatic aging.


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 = $695,670 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	001	15	4/25/2025	NON-COMPETING CONTINUATION	$69,567
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	000	15	2/13/2025	NON-COMPETING CONTINUATION	$626,103
														Subtotal = $695,670

Issue Date FY: 2024 ( Subtotal = $699,576 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	001	14	5/2/2024	NON-COMPETING CONTINUATION	$63,598
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	000	14	1/18/2024	NON-COMPETING CONTINUATION	$635,978
														Subtotal = $699,576

Issue Date FY: 2023 ( Subtotal = $716,736 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	000	13	3/31/2023	NON-COMPETING CONTINUATION	$716,736
														Subtotal = $716,736

Issue Date FY: 2022 ( Subtotal = $740,442 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	000	12	4/15/2022	COMPETING CONTINUATION	$740,442
														Subtotal = $740,442

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	000	11	6/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $474,524 )
2019	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	000	11	12/21/2018	NON-COMPETING CONTINUATION	$474,524
														Subtotal = $474,524

Issue Date FY: 2018 ( Subtotal = $474,524 )
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	004	10	5/14/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$47,453
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	001	10	3/8/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$427,071
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	003	10	4/30/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$190,328
2018	2017	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	002	9	4/30/2018	NON-COMPETING CONTINUATION	-$190,328
2018	2017	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	000	9	3/8/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $474,524

Issue Date FY: 2017 ( Subtotal = $510,772 )
2017	2017	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	000	9	1/13/2017	NON-COMPETING CONTINUATION	$459,694
2017	2017	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	001	9	6/14/2017	NON-COMPETING CONTINUATION	$51,078
														Subtotal = $510,772

Issue Date FY: 2016 ( Subtotal = $506,377 )
2016	2016	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	000	8	1/7/2016	NON-COMPETING CONTINUATION	$460,344
2016	2016	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	001	8	1/26/2016	NON-COMPETING CONTINUATION	$46,033
														Subtotal = $506,377

Issue Date FY: 2015 ( Subtotal = $580,619 )
2015	2015	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	000	7	12/5/2014	COMPETING CONTINUATION	$571,274
2015	2015	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	001	7	12/10/2014	COMPETING CONTINUATION	$9,345
														Subtotal = $580,619

Issue Date FY: 2011 ( Subtotal = $283,225 )
2011	2011	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	000	6	8/1/2011	NON-COMPETING CONTINUATION	$283,225
														Subtotal = $283,225

Issue Date FY: 2010 ( Subtotal = $295,026 )
2010	2010	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Child Health and Human Development Extramural Research	000	5	8/4/2010	NON-COMPETING CONTINUATION	$295,026
														Subtotal = $295,026

Issue Date FY: 2009 ( Subtotal = $298,006 )
2009	2009	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Population Research	000	4	8/3/2009	NON-COMPETING CONTINUATION	$298,006
														Subtotal = $298,006

Issue Date FY: 2008 ( Subtotal = $298,006 )
2008	2008	NEW YORK MEDICAL COLLEGE	ADMINISTRATION BUILDING	VALHALLA	NY	10595	WESTCHESTER	USA	Population Research	000	3	7/14/2008	NON-COMPETING CONTINUATION	$298,006
														Subtotal = $298,006

Issue Date FY: 2007 ( Subtotal = $318,410 )
2007	2007	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Population Research	000	1	9/7/2007	NEW	$318,410
														Subtotal = $318,410

Grand Total All Awards = $6,891,913

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Characterization and prevention of Chemotherapy-Induced Damage to Ovarian Reserve

Award Number: R01HD053112

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: 09/15/2007

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer