Saturday, July 5, 2025 7/5/2025

Deciphering How Esco2 Loss Acts as a Penetrance Modifier

Award Number: R01CA216108
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2017
PERIOD OF PERFORMANCE END DATE: 03/31/2024

Group Awards By:

View Award Description

Deciphering How Esco2 Loss Acts as a Penetrance Modifier - Abstract Li Fraumeni patients, which harbor heterozygous p53 germ line mutation, are highly predisposed to cancers. The penetrance of these individuals can vary greatly; some individuals have tumor onset prior to age 1, while some individual that do not present with cancer by age 74. P53 is the most widely mutated gene in sporadic cancers, therefore understanding the mechanisms that impact tumor penetrance will have great benefit to pre- dicting individual cancer risk. We have made the unique observation that haploinsufficient Esco2 loss, in both zebrafish and mouse, accelerated tumor formation in a p53 heterozygous animals, but not p53 wild type or homozygous null animal. In addition we observe a high proportion of cells in Esco2 heterozygous null animals to have reduced sister chromatid cohesion (SCC). These observations establish our hypothesis that reduced SCC results in increased rates of loss of heterozygosity, which accelerates the timing of tumor initiation and enhanced tumor penetrance. Within this proposal we will address this hypothesis and decipher the mechanism of how Esco2 loss acts as a penetrance modifier. Aim 1, determine if there are accelerated LOH rates, and the type/s of genomic instability that drive accelerated tumorigenesis, in tumors from animals with reduced cohe- sion; Aim 2, determine if the extent of tumor enhancement is dependent on the extent of cohesion dysfunction; Aim 3, determine if biochemically if reduced acetylation by the cohesion establishment factor, ESCO2 lends to reduced cohesion and tumor enhancement. The expected overall impact of the proposed work is that it will fundamentally advance our mechanistic understanding of a how SCC dysfunction impacts tumorigenesis. This will serve as the foundation for future therapeutic intervention and predictive biomarkers of cancer risk.


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 = -$14,254 )
2024	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	000	5	7/24/2024	NON-COMPETING CONTINUATION	-$14,254
														Subtotal = -$14,254

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	000	5	3/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $339,281 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	001	5	6/7/2021	NON-COMPETING CONTINUATION	-$74,306
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	000	5	3/15/2021	NON-COMPETING CONTINUATION	$413,587
														Subtotal = $339,281

Issue Date FY: 2020 ( Subtotal = $426,655 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	000	4	3/16/2020	NON-COMPETING CONTINUATION	$426,655
														Subtotal = $426,655

Issue Date FY: 2019 ( Subtotal = $412,756 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Cause and Prevention Research	001	3	8/2/2019	SUPPLEMENT FOR EXPANSION	$62,911
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	000	3	3/6/2019	NON-COMPETING CONTINUATION	$349,845
														Subtotal = $412,756

Issue Date FY: 2018 ( Subtotal = $354,725 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	001	2	5/23/2018	NON-COMPETING CONTINUATION	$35,473
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	000	2	2/23/2018	NON-COMPETING CONTINUATION	$319,252
														Subtotal = $354,725

Issue Date FY: 2017 ( Subtotal = $359,477 )
2017	2017	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Cancer Biology Research	000	1	3/20/2017	NEW	$359,477
														Subtotal = $359,477

Grand Total All Awards = $1,878,640

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Deciphering How Esco2 Loss Acts as a Penetrance Modifier

Award Number: R01CA216108

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2017

PERIOD OF PERFORMANCE END DATE: 03/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer