P01CA250957
Project Grant
Overview
Grant Description
Mechanisms of the BRCA-Network in Tumorigenesis and Therapeutic Response
(Overall) Abstract:
The faithful repair of DNA damage and efficient resolution of stalled replication forks are fundamental mechanisms by which mammalian cells maintain DNA sequence fidelity and chromosomal integrity during DNA replication and in response to exogenous DNA damage. Defects in DNA repair mechanisms not only contribute to genomic instability and subsequent tumorigenesis, but also can alter the epigenetic landscape of cells and impart therapeutic vulnerabilities that can be exploited clinically.
The investigators participating in this P01 project share common interests in understanding the mechanisms by which cells maintain genomic integrity to suppress tumorigenesis, and in exposing tumor vulnerability to therapy based on mechanistic understandings of the genomic consequences of impaired DNA repair. One particularly strong area of research offered by this team is a multi-disciplinary approach to understanding the basic mechanisms by which the BRCA1-PALB2-BRCA2 complex and associated regulators participate in regulating DNA replication and repair choice. Regulators of the BRCA-network include 53BP1, RNF4, BARD1, TOPBP1, EHMT2 (G9A), MCM10, SLFN11 (mouse SLFN9), and BCCIP. Some of these factors have been a long-standing research focus for investigators in the project team.
The research collaboration is formed around the central themes of how members of this large network of proteins interface with each other to maintain genome integrity, suppress tumor development, and modulate tumor response to cancer therapy. Four projects, two shared resource cores, and an administrative core are proposed to achieve three scientific goals:
1) To reveal novel mechanisms by which the recruitment and function of the BRCA1-PALB2-BRCA2 network is regulated by chromatin context mediated by methylation, sumoylation, and ubiquitination;
2) To refine the roles of the BRCA network in DNA replication, tumor suppression, and define the genomic consequences of BRCA dysfunction; and
3) To explore new opportunities to target defects in the BRCA network for therapeutics in medulloblastoma and breast cancer.
(Overall) Abstract:
The faithful repair of DNA damage and efficient resolution of stalled replication forks are fundamental mechanisms by which mammalian cells maintain DNA sequence fidelity and chromosomal integrity during DNA replication and in response to exogenous DNA damage. Defects in DNA repair mechanisms not only contribute to genomic instability and subsequent tumorigenesis, but also can alter the epigenetic landscape of cells and impart therapeutic vulnerabilities that can be exploited clinically.
The investigators participating in this P01 project share common interests in understanding the mechanisms by which cells maintain genomic integrity to suppress tumorigenesis, and in exposing tumor vulnerability to therapy based on mechanistic understandings of the genomic consequences of impaired DNA repair. One particularly strong area of research offered by this team is a multi-disciplinary approach to understanding the basic mechanisms by which the BRCA1-PALB2-BRCA2 complex and associated regulators participate in regulating DNA replication and repair choice. Regulators of the BRCA-network include 53BP1, RNF4, BARD1, TOPBP1, EHMT2 (G9A), MCM10, SLFN11 (mouse SLFN9), and BCCIP. Some of these factors have been a long-standing research focus for investigators in the project team.
The research collaboration is formed around the central themes of how members of this large network of proteins interface with each other to maintain genome integrity, suppress tumor development, and modulate tumor response to cancer therapy. Four projects, two shared resource cores, and an administrative core are proposed to achieve three scientific goals:
1) To reveal novel mechanisms by which the recruitment and function of the BRCA1-PALB2-BRCA2 network is regulated by chromatin context mediated by methylation, sumoylation, and ubiquitination;
2) To refine the roles of the BRCA network in DNA replication, tumor suppression, and define the genomic consequences of BRCA dysfunction; and
3) To explore new opportunities to target defects in the BRCA network for therapeutics in medulloblastoma and breast cancer.
Funding Goals
TO IDENTIFY CANCER RISKS AND RISK REDUCTION STRATEGIES, TO IDENTIFY FACTORS THAT CAUSE CANCER IN HUMANS, AND TO DISCOVER AND DEVELOP MECHANISMS FOR CANCER PREVENTION AND PREVENTIVE INTERVENTIONS IN HUMANS. RESEARCH PROGRAMS INCLUDE: (1) CHEMICAL, PHYSICAL AND MOLECULAR CARCINOGENESIS, (2) SCREENING, EARLY DETECTION AND RISK ASSESSMENT, INCLUDING BIOMARKER DISCOVERY, DEVELOPMENT AND VALIDATION, (3) EPIDEMIOLOGY, (4) NUTRITION AND BIOACTIVE FOOD COMPONENTS, (5) IMMUNOLOGY AND VACCINES, (6) FIELD STUDIES AND STATISTICS, (7) CANCER CHEMOPREVENTION AND INTERCEPTION, (8) PRE-CLINICAL AND CLINICAL AGENT DEVELOPMENT, (9) ORGAN SITE STUDIES AND CLINICAL TRIALS, (10) HEALTH-RELATED QUALITY OF LIFE AND PATIENT-CENTERED OUTCOMES, AND (11) SUPPORTIVE CARE AND MANAGEMENT OF SYMPTOMS AND TOXICITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO STIMULATE TECHNICAL INNOVATION, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING, AND FOSTER PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY WOMEN AND SOCIALLY/ECONOMICALLY DISADVANTAGED PERSONS.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
New Brunswick,
New Jersey
089011914
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 394% from $2,284,926 to $11,294,260.
Rutgers The State University Of New Jersey was awarded
BRCA-Network Mechanisms in Tumorigenesis and Therapeutic Response
Project Grant P01CA250957
worth $11,294,260
from National Cancer Institute in May 2021 with work to be completed primarily in New Brunswick New Jersey United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.393 Cancer Cause and Prevention Research.
The Project Grant was awarded through grant opportunity National Cancer Institute Program Project Applications (P01 Clinical Trial Optional).
Status
(Ongoing)
Last Modified 6/20/25
Period of Performance
5/1/21
Start Date
4/30/26
End Date
Funding Split
$11.3M
Federal Obligation
$0.0
Non-Federal Obligation
$11.3M
Total Obligated
Activity Timeline
Transaction History
Modifications to P01CA250957
Additional Detail
Award ID FAIN
P01CA250957
SAI Number
P01CA250957-2785995843
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NC00 NIH National Cancer Institute
Funding Office
75NC00 NIH National Cancer Institute
Awardee UEI
YVVTQD8CJC79
Awardee CAGE
6VL59
Performance District
NJ-06
Senators
Robert Menendez
Cory Booker
Cory Booker
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Cancer Institute, National Institutes of Health, Health and Human Services (075-0849) | Health research and training | Grants, subsidies, and contributions (41.0) | $4,539,338 | 100% |
Modified: 6/20/25