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Advanced tools for HCMI model genetic perturbation and metastasis characterization

Award Number: U01CA250565
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/05/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Advanced tools for HCMI model genetic perturbation and metastasis characterization - ABSTRACT The Human Cancer Models Initiative (HCMI) is creating next generation cancer models that will drive the future of cancer precision medicine research. Historical cancer cell lines have been selected for their rapid proliferation on tissue culture plastic, which has made them amenable to high throughput screening such as genome-wide CRISPR/Cas9 knock-out screens. However, the historical lines have large gaps in their representation of the diversity of human cancer, and they may lack physiological relevance given their optimization for rapid proliferation. Next generation HCMI models address these concerns, but will require the development of new methods to make them useful. Specifically, standard approaches to genome editing (involving first creating Cas9- stably expressing lines and then introducing guide RNAs) will not work for slowly proliferating cells often growing in 3D. We will therefore develop all-in-one genome editing vector systems that will make it possible to bring the power of genome editing to HCMI models. In addition, standard viability read-outs of such “drop-out” screens involve the growth of cells over many population doublings. But for slowly proliferating HCMI models, alternative readouts will be required for efficient screening. We will therefore develop short-term single cell RNA sequencing (scRNAseq) methods that will serve as surrogate read-outs for long-term viability. Given the clinical annotation associated with HCMI models, there is also enormous opportunity to expand the use of these models beyond viability measures to more complex, physiologically relevant phenotypes such as organ-specific metastatic potential. We will therefore develop methods that make it possible to determine the metastatic potential for next generation cancer models, and we will create a public resource of the metastasis map (MetMap) for at least 50 HCMI models. All data and protocols will be made publicly available without restriction, all reagents will be made available via Addgene, and all modified models made available to ATCC for distribution. Importantly, throughout the project, all cell models will be rigorously monitored for evidence of genetic and epigenetic drift. At the conclusion of the proposed project, we expect to have generated a set of tools and data that will help propel the future of cancer precision medicine based on next generation cancer models.


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 = -$31,248 )
2025	2022	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	3	12/4/2024	NON-COMPETING CONTINUATION	-$31,248
														Subtotal = -$31,248

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	3	9/5/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $787,646 )
2022	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	3	8/9/2022	NON-COMPETING CONTINUATION	$787,646
														Subtotal = $787,646

Issue Date FY: 2021 ( Subtotal = $789,862 )
2021	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	2	8/9/2021	NON-COMPETING CONTINUATION	$789,862
2021	2020	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	3/16/2021	NEW	$0
														Subtotal = $789,862

Issue Date FY: 2020 ( Subtotal = $789,862 )
2020	2020	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	8/5/2020	NEW	$789,862
														Subtotal = $789,862

Grand Total All Awards = $2,336,122

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Advanced tools for HCMI model genetic perturbation and metastasis characterization

Award Number: U01CA250565

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/05/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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