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Tumor-associated macrophage reprogramming through PARP14 inhibition in muscle-invasive bladder cancer

Award Number: P30CA006516
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project summary This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-21-100. This NCI Early-stage Surgeon Scientist Program proposal for Dr. Filipe de Carvalho describes a research plan and career development program leading up to an academic career as an independent Urologic Oncologist surgeon-scientist investigator. Dr. De Carvalho is a urologist at Brigham and Women’s Hospital committed to an independent research career focused on accelerating the development of therapeutic strategies to target the immune-suppressive tumor microenvironment in bladder cancer. This Early-stage Surgeon Scientist Program will allow Dr. De Carvalho to become proficient in tumor-associated macrophage biology in bladder cancer with the ultimate goal of developing novel macrophage-directed therapeutic strategies for bladder cancer patients. Dr. De Carvalho will be mentored by Dr. Eliezer Van Allen and co- mentors Drs. Kent Mouw and Elizabeth Mittendorf, leaders in bladder cancer genomics and cancer immunology. Dr. Van Allen is Chief of Division of Population Sciences, Dana-Farber Cancer Institute, and has mentored over a dozen of young investigators that moved to successful independent academic positions. Dr. De Carvalho also gathered an outstanding scientific advisory committee and collaborators that excel in mouse models, statistics and cancer genomics to guide career development and scientific progress. The research proposal focuses on tumor-associated macrophages, which are immune cells with a critical role in tumor growth and immune evasion. Recent evidence revealed a therapy-induced conversion of normally anti-tumor TAMs to a tumor-permissive phenotype. The central hypothesis is that cisplatin induces chronic immunosuppressive IFN signaling in cancer cells leading to a TAM-infiltrated phenotype and immune evasion in treatment-resistant tumors. The central hypothesis will be tested by pursuing two specific aims: 1) Determine the mechanism and effectiveness of targeting TAMs to improve sensitivity of bladder cancer to combined cisplatin and immune checkpoint inhibition. 2) Dissect the tumor-TAM crosstalk that mediates cisplatin resistance. These studies are expected to dissect how TAMs inhibit cytotoxic T-cells in cisplatin-resistant bladder cancer in territories of immune evasion across bladder tumors as well as position Dr. De Carvalho to submit a competitive R01 near the completion of this Program.


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 = $0 )
2025	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	000	59	1/15/2025	NON-COMPETING CONTINUATION	$0
2025	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	001	59	1/16/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $13,069,813 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	005	59	4/16/2024	SUPPLEMENT FOR EXPANSION	$20,875
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	000	59	11/22/2023	NON-COMPETING CONTINUATION	$11,441,846
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	007	59	9/5/2024	SUPPLEMENT FOR EXPANSION	-$73,952
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	006	59	4/25/2024	SUPPLEMENT FOR EXPANSION	$221,854
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	004	59	4/16/2024	NON-COMPETING CONTINUATION	$1,271,315
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	002	59	1/26/2024	SUPPLEMENT FOR EXPANSION	$187,875
2024	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	003	58	4/3/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	001	58	12/28/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $13,069,813

Issue Date FY: 2023 ( Subtotal = $13,742,514 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	000	58	1/25/2023	NON-COMPETING CONTINUATION	$12,713,161
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	002	58	6/23/2023	SUPPLEMENT FOR EXPANSION	$208,750
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	005	58	9/18/2023	SUPPLEMENT FOR EXPANSION	$495,880
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	001	58	6/15/2023	NON-COMPETING CONTINUATION	$0
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Centers Support Grants	004	58	9/15/2023	SUPPLEMENT FOR EXPANSION	$100,000
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	003	58	7/24/2023	SUPPLEMENT FOR EXPANSION	$224,723
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	006	58	9/22/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $13,742,514

Issue Date FY: 2022 ( Subtotal = $13,004,730 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	010	57	4/9/2022	COMPETING CONTINUATION	$2,814,368
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	000	57	12/13/2021	COMPETING CONTINUATION	$12,711,730
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	001	57	4/6/2022	SUPPLEMENT FOR EXPANSION	$115,000
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Research Support	011	57	8/19/2022	SUPPLEMENT FOR EXPANSION	$178,000
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	004	56	4/9/2022	SUPPLEMENT FOR EXPANSION	-$95,833
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	003	56	4/9/2022	SUPPLEMENT FOR EXPANSION	-$301,534
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	008	56	4/9/2022	SUPPLEMENT FOR EXPANSION	-$299,999
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	002	56	4/9/2022	NON-COMPETING CONTINUATION	-$1,499,850
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	009	56	4/9/2022	SUPPLEMENT FOR EXPANSION	-$340,000
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	006	56	4/9/2022	SUPPLEMENT FOR EXPANSION	-$197,986
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	005	56	4/9/2022	SUPPLEMENT FOR EXPANSION	-$59,999
2022	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	007	56	4/9/2022	SUPPLEMENT FOR EXPANSION	-$19,167
														Subtotal = $13,004,730

Issue Date FY: 2021 ( Subtotal = $12,790,265 )
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	006	56	9/20/2021	SUPPLEMENT FOR EXPANSION	$19,167
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	007	56	9/21/2021	SUPPLEMENT FOR EXPANSION	$299,999
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	005	56	9/17/2021	SUPPLEMENT FOR EXPANSION	$301,534
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	000	56	11/10/2020	NON-COMPETING CONTINUATION	$11,829,565
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	008	56	9/22/2021	SUPPLEMENT FOR EXPANSION	$340,000
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	001	56	11/17/2020	SUPPLEMENT FOR EXPANSION	$95,833
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	003	56	11/30/2020	SUPPLEMENT FOR EXPANSION	$197,986
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	004	56	12/14/2020	NON-COMPETING CONTINUATION	-$353,818
2021	2021	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	002	56	11/19/2020	SUPPLEMENT FOR EXPANSION	$59,999
														Subtotal = $12,790,265

Issue Date FY: 2020 ( Subtotal = $12,918,673 ) (Continued on the next page)
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	010	55	8/24/2020	SUPPLEMENT FOR EXPANSION	$99,661
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	006	55	6/26/2020	SUPPLEMENT FOR EXPANSION	$182,073
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	013	55	9/1/2020	SUPPLEMENT FOR EXPANSION	$149,753
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	012	55	8/31/2020	SUPPLEMENT FOR EXPANSION	$125,000
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	011	55	8/28/2020	SUPPLEMENT FOR EXPANSION	$299,840
2020	2020	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Centers Support Grants	004	55	4/7/2020	SUPPLEMENT FOR EXPANSION	$50,194
Grand Total All Awards = $299,551,305

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Tumor-associated macrophage reprogramming through PARP14 inhibition in muscle-invasive bladder cancer

Award Number: P30CA006516

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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