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Uncovering diverse genotype-phenotype relationships in prostate cancer

Award Number: DP2CA271301
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
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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Uncovering diverse genotype-phenotype relationships in prostate cancer - Research Summary/Abstract The sheer genetic heterogeneity and complexity of cancer has been laid bare by next-generation sequencing studies of cancer genomes. A major challenge in the post-genomic era of cancer biology is to move beyond descriptive analyses of genomic data and derive functional insights into the complex multigenic interactions that produce complicated phenotypes associated with cancer evolution. Available experimental systems are poorly-suited to address this problem in a systematic and expeditious manner as they generally lack scale, throughput, economy, or biological relevance. We therefore propose the development of a next-generation functional cancer genomics assay that overcomes these limitations and will be employed here to define complicated genotype-to-phenotype relationships in contexts related to prostate cancer initiation and progression. The assay combines the efficient delivery of random, compound genetic perturbations from barcoded lentiviral libraries encoding gain-of-function and/or loss-of-function events; biological selection for a cancer phenotype; and single-cell sequencing analysis to enumerate lentiviral barcodes for the massively parallel association of genotype with phenotype. The major goal of this project is to apply and advance this pioneering strategy to broadly advance our understanding of prostate cancer biology by characterizing compound genetic interactions that (1) transform benign prostate epithelial cells to cancer and establish distinct cancer subtypes, (2) induce neuroendocrine transdifferentiation of prostate cancer, and (3) promote metastatic dissemination. If successful, these studies will characterize and prioritize the functional contributions of multigenic networks to clinically relevant prostate cancer phenotypes. We will also establish multiple new, genetically-defined mouse models of prostate cancer that will better recapitulate the genetic complexity of the human disease. Finally, we anticipate that the next-generation functional cancer genomics strategy will be a flexible and widely applicable experimental tool to rapidly interrogate complex genetic interactions and their impacts on phenotype in many other cancers.


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	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Trans-NIH Research Support	002	4	3/10/2025	EXTENSION WITH OR WITHOUT FUNDS	$760,655
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Trans-NIH Research Support	004	4	3/18/2025	EXTENSION WITH OR WITHOUT FUNDS	$379,005
2025	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	2	3/10/2025	SUPPLEMENT FOR EXPANSION	-$268,726
2025	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Trans-NIH Research Support	003	3	3/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$379,005
2025	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	001	2	3/10/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$491,929
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $945,000 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Trans-NIH Research Support	000	4	9/9/2024	EXTENSION WITH OR WITHOUT FUNDS	$945,000
														Subtotal = $945,000

Issue Date FY: 2023 ( Subtotal = $642,660 )
2023	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	001	2	9/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	000	2	2/14/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Trans-NIH Research Support	002	3	9/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$642,660
														Subtotal = $642,660

Issue Date FY: 2022 ( Subtotal = $268,726 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	006	2	9/20/2022	SUPPLEMENT FOR EXPANSION	$268,726
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	004	1	8/3/2022	NEW	-$1,101,336
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	003	1	7/27/2022	NEW	$0
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	000	1	11/10/2021	NEW	$0
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	001	1	5/27/2022	NEW	-$164,373
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	005	2	8/3/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,101,336
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	002	2	5/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$164,373
														Subtotal = $268,726

Issue Date FY: 2021 ( Subtotal = $1,584,000 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Trans-NIH Research Support	000	1	9/23/2021	NEW	$1,584,000
														Subtotal = $1,584,000

Grand Total All Awards = $3,440,386

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Uncovering diverse genotype-phenotype relationships in prostate cancer

Award Number: DP2CA271301

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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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