Wednesday, December 17, 2025 12/17/2025

Investigating novel synthetic lethal epigenetic interactions in Acute Myeloid Leukemia

Award Number: R01CA258904
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/13/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Investigating novel synthetic lethal epigenetic interactions in Acute Myeloid Leukemia - Project Summary/Abstract Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by aberrant self-renewal and blocked differentiation of myeloid progenitor cells. Many of the oncogenic drivers of AML converge in dysregulation of epigenetic and transcriptional regulation pathways, generating de novo dependencies on these regulators. A handful of epigenetic dependencies have been identified in AML, however, single-agent inhibitors against epigenetic regulators have shown limited therapeutic efficacy in patients with AML. To improve our limited understanding of epigenetic-related synergistic genetic interactions in AML, we developed a highly efficient CRISPR-Cas12a-based method enabling us to perform double deletion genetic screening. Our preliminary studies identified and validated two pairs of novel interacting synthetic sick combinations of epigenetic regulators in AML: bromodomain containing protein 9 (BRD9) and Jumonji domain-containing protein 6 (JMJD6) as well as the lysine acetyltransferase 6 (KAT6) and JMJD6. JMJD6 is a bi-functional arginine demethylase and lysyl-hydroxylase regulating transcription enhancer activation and was identified in both synergistic pairs of epigenetic factor deletions. BRD9 is a component of chromatin remodeling SWI/SNF complex and was previously identified as an AML specific dependency. KAT6A is a histone acetyltransferase and transcriptional co-activator. We hypothesize that BRD9/JMJD6 and KAT6A/JMJD6 interact synergistically at the level of transcription and chromatin. The presence of JMJD6 in both interactions suggests that JMJD6- deficiency sets up a unique transcription and chromatin state that sensitizes AML cells to distinct epigenetic stresses. In Aim 1, we will investigate the synthetic sick interactions of BRD9/JMJD6 and KAT6A/JMJD6 in vitro and in vivo and in Aim 2, we will dissect the AML-specific synthetic sick interactions of BRD9/JMJD6 and KAT6A/JMJD6 at the molecular level. Our proposed studies will offer basic mechanistic insight into how these novel AML synthetic sick epigenetic interactions sustain AML pathogenesis. Successful completion of the proposed studies holds significant promise towards developing innovative epigenetic pathway-directed therapies and revealing fundamental biological insights into the pathogenesis of AML. 1


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: 2026 ( Subtotal = $335,070 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	5	12/10/2025	NON-COMPETING CONTINUATION	$335,070
														Subtotal = $335,070

Issue Date FY: 2025 ( Subtotal = $372,361 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	001	4	8/29/2025	NON-COMPETING CONTINUATION	$37,236
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	4	11/20/2024	NON-COMPETING CONTINUATION	$335,125
														Subtotal = $372,361

Issue Date FY: 2024 ( Subtotal = $358,194 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	3	12/21/2023	NON-COMPETING CONTINUATION	$339,341
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	001	3	4/18/2024	NON-COMPETING CONTINUATION	$18,853
														Subtotal = $358,194

Issue Date FY: 2023 ( Subtotal = $369,504 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	2	1/26/2023	NON-COMPETING CONTINUATION	$369,504
														Subtotal = $369,504

Issue Date FY: 2022 ( Subtotal = $377,046 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	1	12/13/2021	NEW	$377,046
														Subtotal = $377,046

Grand Total All Awards = $1,812,175

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating novel synthetic lethal epigenetic interactions in Acute Myeloid Leukemia

Award Number: R01CA258904

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/13/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer