Thursday, November 21, 2024 11/21/2024

Adipokine Signaling in Melanoma: Unmasking the Obesity Paradox.

Award Number: P30CA044579
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Background: Studies have revealed that obese individuals have longer survival on BRAF-targeted therapy (BRAF/MEKi) when compared to those with normal weight. This phenomenon, termed the "obesity paradox," remains without a mechanistic explanation. Hypothesis/Objective: Our goal is to uncover the mechanisms behind the obesity paradox in melanoma and identify therapeutic targets. We propose that adiponectin, a key adipocyte-secreted adipokine, plays a crucial role by increasing fatty acid uptake within the tumor microenvironment (TME). In obesity, adiponectin levels are reduced compared to normal weight individuals. We hypothesize that adiponectin decreases the effectiveness of BRAF/MEKi by increasing melanoma tumor fatty acid uptake in the TME. Specific Aims: In Aim 1, we will characterize the role of adiponectin within the TME of melanoma tumors in obese and non-obese mice and assess changes following treatment with BRAF/MEKi. In Aim 2, we will determine how sodium-glucose co-transporter 2 (SGLT2) inhibition alters adiponectin release, fatty acid utilization and affects BRAF/MEKi responses. Study Design: We will employ a diet-induced obesity (DIO) model in C57BL/6J mice implanted with YUMMER1.7 cells to compare adipokine release, fatty acid oxidation, adipocyte transcriptome, and immune responses between obese and non-obese mice treated with BRAF/MEKi. We will use an adiponectin knockout mouse model to explore the role of adiponectin through exogenous delivery versus its absence under similar conditions. Lastly, we will evaluate BRAF/MEKi responses in the DIO model coupled with SGLT2 inhibition, a common diabetes medication with effects on fatty acid oxidation. Impact: Our project diverges from conventional research by focusing on obesity as a favorable condition to emulate. We will elucidate how obesity alters the TME and how adiponectin affects melanoma responses to BRAF/MEKi. We anticipate discovering a unique therapeutic target that can be quickly translated into clinical practice. I firmly believe that the National Cancer Institute Early-Stage Surgeon Scientist (ESSP) program is tailor-made for my career advancement as a surgeon scientist. This program's comprehensive research training, professional development, and abundant resources will significantly accelerate my path to research independence. By participating in the ESSP, I aim to swiftly transition into a role as a principal investigator dedicated to research with direct implications for patient care and help further nurture other future surgeon scientists.


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 = -$66,129 )
2025	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	000	29	10/1/2024	SUPPLEMENT FOR EXPANSION	-$66,129
														Subtotal = -$66,129

Issue Date FY: 2024 ( Subtotal = $2,804,582 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	000	33	3/6/2024	NON-COMPETING CONTINUATION	$2,342,436
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	002	33	4/18/2024	SUPPLEMENT FOR EXPANSION	$201,875
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	001	33	4/17/2024	NON-COMPETING CONTINUATION	$260,271
														Subtotal = $2,804,582

Issue Date FY: 2023 ( Subtotal = $2,602,707 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	000	32	1/19/2023	NON-COMPETING CONTINUATION	$2,602,707
														Subtotal = $2,602,707

Issue Date FY: 2022 ( Subtotal = $2,602,707 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	002	31	6/7/2022	COMPETING CONTINUATION	$1,189,312
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	000	31	1/24/2022	COMPETING CONTINUATION	$2,602,707
2022	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	001	30	6/7/2022	NON-COMPETING CONTINUATION	-$1,189,312
														Subtotal = $2,602,707

Issue Date FY: 2021 ( Subtotal = $2,602,707 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	001	30	3/2/2021	NON-COMPETING CONTINUATION	$2,602,707
2021	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	000	29	10/15/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $2,602,707

Issue Date FY: 2020 ( Subtotal = $3,002,553 )
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	001	29	1/30/2020	SUPPLEMENT FOR EXPANSION	$124,862
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	000	29	1/29/2020	NON-COMPETING CONTINUATION	$2,602,707
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	002	29	1/31/2020	SUPPLEMENT FOR EXPANSION	$25,000
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	003	29	9/2/2020	SUPPLEMENT FOR EXPANSION	$100,001
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	004	29	9/3/2020	SUPPLEMENT FOR EXPANSION	$149,983
														Subtotal = $3,002,553

Issue Date FY: 2019 ( Subtotal = $3,230,899 )
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	004	28	1/29/2019	SUPPLEMENT FOR EXPANSION	$29,346
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	003	28	1/28/2019	SUPPLEMENT FOR EXPANSION	$249,724
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	007	28	2/1/2019	SUPPLEMENT FOR EXPANSION	$60,000
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	006	28	1/31/2019	SUPPLEMENT FOR EXPANSION	$91,989
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	002	28	1/25/2019	SUPPLEMENT FOR EXPANSION	$146,172
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	005	28	1/30/2019	SUPPLEMENT FOR EXPANSION	$50,961
2019	2019	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	001	28	1/25/2019	NON-COMPETING CONTINUATION	$2,602,707
2019	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	000	27	11/14/2018	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $3,230,899

Issue Date FY: 2018 ( Subtotal = $3,336,791 )
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	002	27	5/23/2018	NON-COMPETING CONTINUATION	$259,934
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	001	27	2/13/2018	SUPPLEMENT FOR EXPANSION	$222,620
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	008	27	8/24/2018	SUPPLEMENT FOR EXPANSION	$107,460
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	003	27	5/24/2018	SUPPLEMENT FOR EXPANSION	$24,735
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	000	27	1/18/2018	NON-COMPETING CONTINUATION	$2,339,415
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	007	27	8/22/2018	SUPPLEMENT FOR EXPANSION	$174,039
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	006	27	8/20/2018	SUPPLEMENT FOR EXPANSION	$48,726
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	004	27	6/7/2018	SUPPLEMENT FOR EXPANSION	$35,000
2018	2018	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	005	27	7/12/2018	SUPPLEMENT FOR EXPANSION	$124,862
2018	2015	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	009	24	9/17/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,336,791

Issue Date FY: 2017 ( Subtotal = $2,803,591 )
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	007	26	9/19/2017	SUPPLEMENT FOR EXPANSION	$104,087
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	001	26	2/15/2017	SUPPLEMENT FOR EXPANSION	$125,000
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	002	26	3/1/2017	COMPETING CONTINUATION	$23,808
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	006	26	6/20/2017	COMPETING CONTINUATION	$401,223
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	000	26	2/1/2017	COMPETING CONTINUATION	$2,149,473
2017	2017	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	005	26	5/15/2017	COMPETING CONTINUATION	$490,889
2017	2016	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Cause and Prevention Research	003	25	5/15/2017	EXTENSION WITH OR WITHOUT FUNDS	-$365,889
2017	2016	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Cancer Centers Support Grants	004	25	5/15/2017	SUPPLEMENT FOR EXPANSION	-$125,000
														Subtotal = $2,803,591

Grand Total All Awards = $66,610,744

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Adipokine Signaling in Melanoma: Unmasking the Obesity Paradox.

Award Number: P30CA044579

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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