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Oncogenic functions of mutant p53

Award Number: R01CA166974
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract The tumor suppressor gene, p53, has pleiotropic functions that quash tumor development. One of its most important functions is to prevent the genome from sustaining DNA damage in order to prevent the propagation of genetic lesions into daughter cells. Given the high degree of genetic alterations in cancer, it is not surprising that p53 is frequently inactivated. The most common form of genetic lesions in the p53 gene are point mutations in the DNA binding domain. These missense mutations typically inactivate the p53’s tumor suppressor activity while simultaneously generating an oncogenic protein. The presence of mutant p53 correlates with increased chromosomal instability leading to loss of tumor suppressor genes and amplification of oncogenes. It has become increasingly recognized that the cGAS/STING/TBK1/IRF3 innate immune response signaling pathway plays a crucial role in detecting genetic alterations and launching cell intrinsic and extrinsic responses to suppress aberrant cells that harbor genetic defects. In this proposal, we that mutant p53 suppresses signaling through the cGAS/STING pathway and thereby dictates how cells respond to its activation. We propose three aims to determine the mechanism by which mutant p53 controls cGAS/STING signaling, and the cell intrinsic and extrinsic consequences of modulation of this pathway. The completion of these studies will help guide how to therapeutically approach cancers based on their p53 status.


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 = $297,867 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	000	9	1/8/2024	NON-COMPETING CONTINUATION	$297,867
														Subtotal = $297,867

Issue Date FY: 2023 ( Subtotal = $324,342 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	000	8	2/17/2023	NON-COMPETING CONTINUATION	$324,342
														Subtotal = $324,342

Issue Date FY: 2022 ( Subtotal = $325,965 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	002	7	5/10/2022	COMPETING CONTINUATION	$0
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	001	7	12/29/2021	COMPETING CONTINUATION	$330,963
2022	2019	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	6	11/9/2021	SUPPLEMENT FOR EXPANSION	-$4,998
														Subtotal = $325,965

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	001	6	5/21/2021	SUPPLEMENT FOR EXPANSION	$4,998
2021	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	000	6	11/13/2020	SUPPLEMENT FOR EXPANSION	-$4,998
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $50,000 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Cause and Prevention Research	001	6	8/12/2019	SUPPLEMENT FOR EXPANSION	$50,000
2019	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	000	6	5/6/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $50,000

Issue Date FY: 2017 ( Subtotal = $327,850 )
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	000	6	4/27/2017	NON-COMPETING CONTINUATION	$295,065
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	001	6	6/7/2017	NON-COMPETING CONTINUATION	$32,785
														Subtotal = $327,850

Issue Date FY: 2016 ( Subtotal = $299,445 )
2016	2016	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	003	5	5/2/2016	NON-COMPETING CONTINUATION	$299,445
2016	2015	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Cause and Prevention Research	000	3	10/29/2015	SUPPLEMENT FOR EXPANSION	$0
2016	2015	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	001	3	12/14/2015	NON-COMPETING CONTINUATION	-$201,758
2016	2015	SUNY, STONY BROOK	OFFICE OF RESEARCH SERVICES	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Biology Research	002	4	12/16/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$201,758
														Subtotal = $299,445

Issue Date FY: 2015 ( Subtotal = $356,712 )
2015	2015	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Cause and Prevention Research	001	3	4/16/2015	SUPPLEMENT FOR EXPANSION	$46,499
2015	2015	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	000	3	4/15/2015	NON-COMPETING CONTINUATION	$310,213
														Subtotal = $356,712

Issue Date FY: 2014 ( Subtotal = $340,673 )
2014	2014	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Cause and Prevention Research	001	2	9/4/2014	SUPPLEMENT FOR EXPANSION	$39,766
2014	2014	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	000	2	5/1/2014	NON-COMPETING CONTINUATION	$300,907
														Subtotal = $340,673

Issue Date FY: 2013 ( Subtotal = $310,213 )
2013	2013	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	001	1	7/2/2013	NEW	$77,554
2013	2013	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	000	1	4/30/2013	NEW	$232,659
														Subtotal = $310,213

Grand Total All Awards = $2,633,067

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Oncogenic functions of mutant p53

Award Number: R01CA166974

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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