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Intersectional genetics-based biosensors for dormant cancer cells

Award Number: R61CA278402
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Intersectional genetics-based biosensors for dormant cancer cells - PROJECT SUMMARY/ABSTRACT Background: Metastasis in distant organs years after treatment is the primary cause of cancer death. Late progression occurs through the reactivation of dormant tumor cells that disseminated early in the disease. To date, no therapy has been designed to target those cells and the lack of understanding on their biology prevents the development of selective strategies to kill them. We aim to gain molecular insight into the gene regulatory signature of the cancer dormancy state and use this information to devise a dormant cancer cell biosensor that will allow us to identify, profile, and genetically manipulate them in vivo. Hypothesis: We hypothesize that the application of intersectional genetics tools to define the unique transcriptional profile of dormant cells will reveal vulnerabilities that could be exploited to eliminate those cells. Specific Aims: Aim 1. To obtain and validate the enhancer activity profiles of dormant cancer cells in an in vivo context Aim 2. To develop a dormant cancer cell biosensor and test its in vivo potential to selectively identify dormant cancer cells. Study design/Methods: To increase the specificity of dormant cancer cell identification in vivo, reduce side- effects on non-target normal cells, and allow the systematization of the generation of dormant cell-specific biosensors and its downstream applications, such as targeted cell ablation therapies, we propose to develop a new dormant cell biosensor that bypasses cell-surface marker requirements distinguishing them instead via intracellular properties that can be harnessed to allow the precise and exclusive genetic manipulation of these cells within the body. We will validate our biosensor in vivo by using cellular dormancy models and intravital two- photon microscopy. Relevance: The mechanisms of cancer cell dormancy are poorly understood, hence the options available for their targeted treatment to prevent metastasis are limited. Here, we propose to use state-of-the-art genomic activity profiling technology to gain molecular insight into the genetic program that defines the cancer dormancy state in vivo. We will then couple our unique computational and synthetic biology know-how to define unique signatures of the dormancy program to engineer genetic sensors that can be systemically-delivered into the body to find dormant cancer cells. With this strategy, we hope to develop strategies to eliminate metastatic dormant cells, the source of metastasis.


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 = $213,638 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Biology Research	000	3	9/5/2025	NON-COMPETING CONTINUATION	$213,638
														Subtotal = $213,638

Issue Date FY: 2024 ( Subtotal = $190,495 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Biology Research	000	2	6/10/2024	NON-COMPETING CONTINUATION	$190,495
														Subtotal = $190,495

Issue Date FY: 2023 ( Subtotal = $302,272 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Biology Research	001	1	9/13/2023	SUPPLEMENT FOR EXPANSION	$84,500
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Biology Research	000	1	4/19/2023	NEW	$217,772
														Subtotal = $302,272

Grand Total All Awards = $706,405

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Intersectional genetics-based biosensors for dormant cancer cells

Award Number: R61CA278402

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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