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Mechanisms of UV-Mediated Melanoma Development

Award Number: R01CA237213
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/04/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Mechanisms of UV-Mediated Melanoma Development - ABSTRACT Biological processes that guard against melanoma are generally successful. Thus, to understand melanoma etiology we must identify the flaws in these mechanisms that lead to tumorigenesis. This proposal will elucidate deficiencies in the cellular mechanisms that combat UV damage and define the tumorigenic consequences of melanocyte pigment production. Our studies will improve mechanistic understanding of melanoma etiology by revealing gaps in the physiological processes that block UV carcinogenesis. We hypothesize that melanoma progression is influenced by melanin production and accelerated by the persistence of unresolved DNA lesions specific to the initiating UV wavelength. To test this hypothesis we will define how full-spectrum (UVA/B) and partitioned solar irradiation (UVA or UVB) influence the onset and progression of melanoma in genetically relevant, Braf- and Nras-mutant mouse models. We will elucidate transcriptional and mutational patterns enriched in tumors driven by each UV spectrum and oncogene, and use this information to define how UV lesions escape repair (Aim 1). Next, we will cross our models to eumelanotic (black), amelanotic (albino) or pheomelanotic (red/yellow) alleles to determine how melanin impacts the formation, progression and immunotherapeutic response of Braf- and Nras-mutant melanomas accelerated by different UV spectra (Aim 2). Knowledge gained from these experiments will aid in the development of melanoma preventatives that progress beyond sunscreens, including interventions that mitigate UV carcinogenesis after an exposure or reduce melanoma risk in individuals with more photosensitive skin types.


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 = $402,423 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	001	5	5/22/2024	SUPPLEMENT FOR EXPANSION	$71,136
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	000	5	5/13/2024	NON-COMPETING CONTINUATION	$331,287
														Subtotal = $402,423

Issue Date FY: 2023 ( Subtotal = $415,678 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	001	4	5/22/2023	SUPPLEMENT FOR EXPANSION	$73,383
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	000	4	5/17/2023	NON-COMPETING CONTINUATION	$342,295
														Subtotal = $415,678

Issue Date FY: 2022 ( Subtotal = $440,006 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	001	2	7/22/2022	SUPPLEMENT FOR EXPANSION	$23,812
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	002	3	7/25/2022	SUPPLEMENT FOR EXPANSION	$73,382
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	000	3	5/2/2022	NON-COMPETING CONTINUATION	$342,812
														Subtotal = $440,006

Issue Date FY: 2021 ( Subtotal = $357,986 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	000	2	5/28/2021	NON-COMPETING CONTINUATION	$357,986
														Subtotal = $357,986

Issue Date FY: 2020 ( Subtotal = $368,708 )
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Cause and Prevention Research	000	1	9/4/2020	NEW	$368,708
														Subtotal = $368,708

Grand Total All Awards = $1,984,801

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Mechanisms of UV-Mediated Melanoma Development

Award Number: R01CA237213

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/04/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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