Sunday, October 19, 2025 10/19/2025

Mechanism and therapeutic opportunities of targeting the Tudor domain

Award Number: R01CA278050
ORGANIZATION: NATIONAL CANCER INSTITUTE
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: 02/16/2025

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Mechanism and therapeutic opportunities of targeting the Tudor domain - PROJECT SUMMARY/ABSTRACT MLL-rearranged (MLL-r) leukemias account for 5-10% of human acute leukemia and is associated with poor prognosis. The unmet clinical needs and the lack of an effective targeted therapy to the MLL-r leukemias emphasize the need for novel regimens. Recent cancer epigenetics studies discovered a central role for the histone H3 lysine 79 (H3K79) methyltransferase DOT1L in MLL-r leukemogenesis. Important clinical responses have been noted with DOT1L inhibitor treatment as a single agent, however, it is expected that combination treatments will be necessary. Our preliminary studies based on a Tudor domain focused CRISPR screen in MLL-r leukemia identified SGF29 as a novel vulnerability in MLL-r leukemia. The objective of this application is to determine the critical epigenetic mechanisms that mediate the availability of KAT2A/B to maintain H3K9ac and oncogene expression in MLL-r leukemia. Our central hypothesis is that SGF29, an H3K4me3 reader protein, mediates recruitment of KAT2A/B to maintain histone H3K9ac and MYC oncogenic program in MLL-r leukemia. We will dissect the SGF29-mediated epigenetic mechanisms (Aim 1) and investigate the efficacy of SGF29 targeting (alone or in combination with DOT1L inhibition) as a novel therapy in MLL-r leukemia (Aim 2). This study is innovative because (1) it introduces a novel concept of simultaneously targeting multiple components of an epigenetic network to efficiently suppress the cancer programs, and (2) it establishes a brand new genetic screen approach for a sub-protein level functional pocket and drug discovery. The impact of this research will be of significance because (1) it immediately provides novel therapeutic opportunities against the difficult-to-treat MLL-r leukemias, and (2) it will help identify novel functional elements in epigenetic regulators for future pharmaceutical targeting.


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 = $511,281 )
2025	2025	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Biology Research	000	3	11/20/2024	NON-COMPETING CONTINUATION	$460,155
2025	2025	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Biology Research	004	3	9/22/2025	NON-COMPETING CONTINUATION	$68,722
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Biology Research	003	4	9/19/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$375,715
2025	2025	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Biology Research	002	3	9/18/2025	NON-COMPETING CONTINUATION	-$444,438
2025	2025	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Biology Research	001	3	6/25/2025	NON-COMPETING CONTINUATION	$51,127
														Subtotal = $511,281

Issue Date FY: 2024 ( Subtotal = $485,717 )
2024	2024	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Biology Research	000	2	11/29/2023	NON-COMPETING CONTINUATION	$460,153
2024	2024	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Biology Research	001	2	4/18/2024	NON-COMPETING CONTINUATION	$25,564
														Subtotal = $485,717

Issue Date FY: 2023 ( Subtotal = $510,917 )
2023	2023	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Cancer Biology Research	000	1	11/28/2022	NEW	$510,917
														Subtotal = $510,917

Grand Total All Awards = $1,507,915

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Mechanism and therapeutic opportunities of targeting the Tudor domain

Award Number: R01CA278050

ORGANIZATION: NATIONAL CANCER INSTITUTE

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: 02/16/2025

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