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Center for Systems-level Study of Metastasis

Award Number: U54CA261701
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/23/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Center for Systems-level Study of Metastasis - Project Summary: Metastatic disease is a complex, dynamic and emergent process that requires collective and coordinated interactions between many cell types, metabolites and the host. There is substantial clinico- pathologic and experimental evidence for critical roles of neural innervation, lymphatic interactions, metabolites and endothelial cells in regulating metastatic progression by altering cancer and immune cell functions. As such, these cellular interactions likely shape metastatic progression, responses to therapy and metastatic dissemination. However, we have a limited understanding of how these components coordinately regulate metastatic progression. This application describes a series of highly innovative multidisciplinary molecular, cell- biological, metabolic, massively-parallel single-cell sequencing and organismal methods applied towards defining the dynamic and emergent mechanisms by which neural cells, lymphatics, immune cells and metabolites interact to coordinately regulate metastatic progression—contributing to a systems-level understanding of metastasis. We aim to (i) define the role of neural innervation on metastatic progression by characterizing neuro- tumor and neuro-immune interactions and identifying neural signals and their pro-metastatic mechanisms of action, (ii) determine how endothelial cells regulate innervation of metastatic tumors, (iii) define the role of regionalized lymphatic interactions in driving metastatic progression and anti-metastatic immunity, (iv) assess the role of neuro-immune and neuro-epithelial interactions on early metastatic dissemination and colonization, (v) identify metabolite and protein signals that drive metastatic colonization, (vi) discover tumoral transcription factors and RNA-binding proteins that act downstream of neural and metabolic signals to drive emergent pro- metastatic gene expression programs, and (vii) determine the impact of standard chemotherapy on these diverse cellular interactions and metabolic determinants of metastatic progression. Our proposed MetNet Center will enhance our understanding of how interactions and crosstalk between cancer cells with nervous system cells, lymphatics, vasculature and immune cells enables emergence of metastatic disease. We will also assess how therapy impacts specific cell-cell and metabolic interactions of metastatic cells and provide insights into the impact of specific cellular interactions in the primary microenvironment on metastatic dissemination, including early dissemination. These findings will generate an integrated, systems-level understanding of metastasis, enabling development of a new generation of anti-cancer therapies that prevent critical emergent coordinated pro-metastatic interactions.


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 = $1,678,554 )
2025	2025	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	001	5	9/8/2025	NON-COMPETING CONTINUATION	$1,678,554
2025	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	4	4/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,678,554

Issue Date FY: 2024 ( Subtotal = $1,920,408 )
2024	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	003	4	9/17/2024	SUPPLEMENT FOR EXPANSION	$179,325
2024	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	001	4	8/6/2024	NON-COMPETING CONTINUATION	$1,557,708
2024	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	002	4	9/10/2024	SUPPLEMENT FOR EXPANSION	$183,375
2024	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	3	2/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,920,408

Issue Date FY: 2023 ( Subtotal = $1,645,303 )
2023	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	3	8/17/2023	NON-COMPETING CONTINUATION	$1,645,303
2023	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	001	3	9/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,645,303

Issue Date FY: 2022 ( Subtotal = $1,645,303 )
2022	2022	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	2	8/22/2022	NON-COMPETING CONTINUATION	$1,645,303
														Subtotal = $1,645,303

Issue Date FY: 2021 ( Subtotal = $1,696,261 )
2021	2021	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Centers Support Grants	000	1	9/23/2021	NEW	$1,696,261
														Subtotal = $1,696,261

Grand Total All Awards = $8,585,829

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Center for Systems-level Study of Metastasis

Award Number: U54CA261701

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/23/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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