Saturday, July 5, 2025 7/5/2025

RAD51 paralog function in cancer predisposition and genome integrity

Award Number: R01ES031796
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2026

Group Awards By:

View Award Description

RAD51 paralog function in cancer predisposition and genome integrity - Project Summary/Abstract: Accurate repair of DNA damage is critical for genetic stability, and for preventing aging-related degeneration and cancer. We are working to identify key factors that regulate accurate repair of DNA double-strand breaks (DSBs) through the error-free homologous recombination (HR) pathway. DSBs can arise from many sources including endogenous replication fork damage, exogenous environmental toxicants, or oxidative stresses induced by endogenous sources and during pro-inflammatory responses to toxicant injury. We found that the RAD51 paralogs are critical for promoting HR and hence for suppressing error-prone repair mechanisms. Over 300 studies link mutations in human RAD51 paralogs with cancer, and women with breast or ovarian cancer are now screened for RAD51 paralog mutations. However, it remains largely unknown which RAD51 paralog mutations are pathogenic and how these mutations sensitize individuals to environmentally induced-DNA damage due to our lack of functional analysis of either the wild-type or mutated proteins. We do not know how these proteins are recruited, their functional components, or the disruptions caused by mutations or polymorphisms in the RAD51 paralogs. This knowledge gap results from low abundance of endogenous RAD51 paralog proteins, insolubility of the recombinant proteins, as well as embryonic lethality in knock-out mice. We are therefore using genetic, biochemical, and cell biological approaches to characterize RAD51 paralog function upon exposure to DSB inducing agents. We will use ionizing radiation (IR) and bleomycin as model agents for environmentally relevant DSB-inducing agents. Using complementary approaches in combination with high-throughput genetic screening, we are now uniquely poised to address how RAD51 paralog mutations predispose individuals to human cancer and thus, to identify opportunities for determining who is at risk for cancer development upon exposure to environmental carcinogens. Our ultimate goal is to enable development of precision medicine strategies for individual patients whose tumors harbor a RAD51 paralog mutation profile.


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 = $416,996 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Environmental Health	000	5	3/4/2025	NON-COMPETING CONTINUATION	$416,996
														Subtotal = $416,996

Issue Date FY: 2024 ( Subtotal = $451,972 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Environmental Health	000	4	2/28/2024	NON-COMPETING CONTINUATION	$451,972
														Subtotal = $451,972

Issue Date FY: 2023 ( Subtotal = $461,230 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Environmental Health	001	3	4/25/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$461,230
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Environmental Health	004	3	6/27/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$271,325
2023	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Environmental Health	003	2	6/27/2023	NON-COMPETING CONTINUATION	-$122
2023	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Environmental Health	002	2	5/15/2023	NON-COMPETING CONTINUATION	-$271,203
2023	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Environmental Health	000	2	4/25/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $461,230

Issue Date FY: 2022 ( Subtotal = $469,943 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Environmental Health	000	2	12/16/2021	NON-COMPETING CONTINUATION	$469,943
														Subtotal = $469,943

Issue Date FY: 2021 ( Subtotal = $446,797 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Environmental Health	000	1	3/15/2021	NEW	$446,797
														Subtotal = $446,797

Grand Total All Awards = $2,246,938

Top

All Categories

About

Search

Reports

Data Submission

Award Information

RAD51 paralog function in cancer predisposition and genome integrity

Award Number: R01ES031796

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer