Wednesday, February 18, 2026 2/18/2026

Shaping DNA Damage Response Networks Via Histone H2A Variants

Award Number: R01CA198279
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Shaping DNA Damage Response Networks Via Histone H2A Variants - PROJECT SUMMARY Genome organization is driven by chromatin, the fundamental unit being the nucleosome that is made up of histone proteins. In addition to canonical histones, histone variants exist that diversify chromatin and play specialized roles in genome maintenance. Although best studied in transcription, histone H2A variants in particular are emerging as critical participants in DNA damage responses including DNA repair that protect cells from the constant threat of endogenous DNA damage and mutations, which are known to be drivers of human diseases including cancer. Based on our studies, macroH2A1.2 plays vital functions in DNA repair and DNA damage associated transcriptional regulation. Here, we will employ innovative biochemical and cell-based systems to identify mechanistically how macroH2A histone variant, in collaboration with PARP1 and the histone demethylase KDM5A, orchestrate DNA damage response functions. Specifically, we will determine how macroH2A and KDM5A are involved in radiation and PARP inhibitor (PARPi) responses. We hypothesize that PARPi can interfere with KDM5A function and that effector proteins promote the function of these factors at breaks, including transcription regulation and HR repair. We will identify macroH2A functions in DNA repair and therapeutic responses using cancer and non-transformed cell lines. Using cell complementation, we will define the specific interactions, domains and modifications involved in these pathways and responses. Although macroH2A, KDM5A and other macroH2A effector proteins are known to be involved in cancer, these studies will identify their genome integrity functions and importance for DNA damage responses involving radiation and PARPi. Our long-term goals are to define mechanistically how chromatin and its associated factors contribute to genome integrity and how deficiencies in these pathways can be targeted in cancer. This proposed work contributes to these goals through a combination of genetic, biochemical and cellular approaches in human cells to identify and define macroH2A pathways that promote genome integrity, including through DNA repair and transcriptional responses. These studies will deliver new mechanistic insights into how this pathways protects the genome and determine if dysregulation of this pathway in cancer can provide opportunities for therapeutic interventions.


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 = $365,376 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Cause and Prevention Research	002	9	4/25/2025	NON-COMPETING CONTINUATION	$340,375
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Cause and Prevention Research	004	9	5/26/2025	NON-COMPETING CONTINUATION	$37,819
2025	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cancer Cause and Prevention Research	003	7	4/30/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cancer Cause and Prevention Research	000	7	3/3/2025	NON-COMPETING CONTINUATION	-$166,525
2025	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Cause and Prevention Research	001	8	3/4/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$153,707
														Subtotal = $365,376

Issue Date FY: 2024 ( Subtotal = $366,851 )
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cancer Cause and Prevention Research	000	7	3/14/2024	NON-COMPETING CONTINUATION	$347,543
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cancer Cause and Prevention Research	001	7	4/16/2024	NON-COMPETING CONTINUATION	$19,308
														Subtotal = $366,851

Issue Date FY: 2023 ( Subtotal = $386,159 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cancer Cause and Prevention Research	000	6	4/7/2023	COMPETING CONTINUATION	$386,159
														Subtotal = $386,159

Issue Date FY: 2022 ( Subtotal = -$2,266 )
2022	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	000	5	8/30/2022	NON-COMPETING CONTINUATION	-$2,266
														Subtotal = -$2,266

Issue Date FY: 2020 ( Subtotal = $352,824 )
2020	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	000	5	3/2/2020	NON-COMPETING CONTINUATION	$352,824
														Subtotal = $352,824

Issue Date FY: 2019 ( Subtotal = $342,238 )
2019	2019	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	000	4	3/13/2019	NON-COMPETING CONTINUATION	$342,238
														Subtotal = $342,238

Issue Date FY: 2018 ( Subtotal = $352,824 )
2018	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	001	3	5/23/2018	NON-COMPETING CONTINUATION	$35,283
2018	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	000	3	3/13/2018	NON-COMPETING CONTINUATION	$317,541
														Subtotal = $352,824

Issue Date FY: 2017 ( Subtotal = $385,319 )
2017	2017	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	002	2	8/9/2017	NON-COMPETING CONTINUATION	$32,495
2017	2017	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	000	2	2/23/2017	NON-COMPETING CONTINUATION	$317,541
2017	2017	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Cancer Biology Research	001	2	6/7/2017	NON-COMPETING CONTINUATION	$35,283
														Subtotal = $385,319

Issue Date FY: 2016 ( Subtotal = $351,452 )
2016	2016	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Cancer Biology Research	000	1	4/5/2016	NEW	$351,452
														Subtotal = $351,452

Grand Total All Awards = $2,900,778

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Shaping DNA Damage Response Networks Via Histone H2A Variants

Award Number: R01CA198279

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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