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The histone demethylase JMJD1C in human Acute Myeloid Leukemia

Award Number: R37CA229751
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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The histone demethylase JMJD1C in human Acute Myeloid Leukemia - PROJECT SUMMARY Current therapy for acute myeloid leukemia (AML) is inadequate. Despite newly available therapeutics agents, the overall survival rate for patients with the disease is still poor. It was previously shown that JMJD1C, a histone demethylase of KDM3 (lysine demethylase 3) family, is required for AML leukemogenesis but largely dispensable for steady state hematopoiesis and therefore, a potential therapeutic target in AML. In a recent study, loss of JMJD1C in leukemia cells was shown to lead to elevated RAS signaling pathway and increased sensitivity to inhibitors against the pathway. Furthermore, the presence of RAS activating mutations that are common in AML confer resistance to JMJD1C loss. These data led to the hypothesis that targeting RAS pathway in combination with JMJD1C would be more effective in eliminating leukemia cells harboring activating RAS mutations. This hypothesis will be tested by the following plan: i) efficacy of combining JMJD1C modulation with RAS pathway inhibitors in treating AML with RAS mutations will be tested in mouse as well as xenograft models of AML; ii) molecular mechanism of resistance to JMJD1C loss in AML with RAS mutations, as well as the role of biomolecule condensates, emerging key regulator of transcription and AML leukemogenesis, in mediating the molecular function of JMJD1C in AML will be studied. Overall, the proposed project, once accomplished, will provide rational for the design of novel combination therapy for AML with co-occurring activating RAS mutations.


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 = $487,500 )
2025	2025	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	000	7	4/10/2025	NON-COMPETING CONTINUATION	$438,750
2025	2025	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	001	7	5/22/2025	NON-COMPETING CONTINUATION	$48,750
														Subtotal = $487,500

Issue Date FY: 2024 ( Subtotal = $429,011 )
2024	2024	J. CRAIG VENTER INSTITUTE, INC.	4120 CAPRICORN LN	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Biology Research	002	6	8/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$463,125
2024	2023	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	003	5	8/30/2024	NON-COMPETING CONTINUATION	$39,413
2024	2023	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	000	5	8/12/2024	NON-COMPETING CONTINUATION	-$34,114
2024	2023	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	001	5	8/26/2024	NON-COMPETING CONTINUATION	-$39,413
														Subtotal = $429,011

Issue Date FY: 2023 ( Subtotal = $373,265 )
2023	2023	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	000	5	4/24/2023	NON-COMPETING CONTINUATION	$373,265
														Subtotal = $373,265

Issue Date FY: 2022 ( Subtotal = $380,916 )
2022	2022	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	000	4	5/20/2022	NON-COMPETING CONTINUATION	$380,916
														Subtotal = $380,916

Issue Date FY: 2021 ( Subtotal = $381,528 )
2021	2021	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	000	3	5/5/2021	NON-COMPETING CONTINUATION	$381,528
														Subtotal = $381,528

Issue Date FY: 2020 ( Subtotal = $389,183 )
2020	2020	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	001	2	5/22/2020	NON-COMPETING CONTINUATION	$0
2020	2020	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	000	2	4/28/2020	NON-COMPETING CONTINUATION	$389,183
														Subtotal = $389,183

Issue Date FY: 2019 ( Subtotal = $388,975 )
2019	2019	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Cancer Biology Research	000	1	5/16/2019	NEW	$388,975
														Subtotal = $388,975

Grand Total All Awards = $2,830,378

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The histone demethylase JMJD1C in human Acute Myeloid Leukemia

Award Number: R37CA229751

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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