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Tracing Hypoxic State and Hypoxia Memory in Glioblastoma Progression

Award Number: R21NS125700
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2023

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Tracing Hypoxic State and Hypoxia Memory in Glioblastoma Progression - Hypoxia is linked to worse prognosis for cancers, including glioblastoma (GBM), the most common and highly lethal primary brain tumor. Hypoxic tumor cells are thought to be better equipped to survive therapy and spawn tumor recurrence, however, the trajectory of hypoxic cells during GBM expansion and their roles in recurrent GBM after therapy remain poorly understood. The main goal of this proposal is to apply a dual genetically encoded hypoxia-sensitive reporter system with lineage tracing capability to systematically characterize hypoxic tumor cells during GBM progression. The dual reporter system distinguishes tumor cells that are acutely hypoxic (marked by green fluorescence) from those with a history of hypoxia exposure (permanently marked with red fluorescence). Their cell fate will be traced across time and space during GBM progression in both primary and recurrent GBM models. The cellular study will be coupled with gene expression analysis on single cell level to unravel the molecular underpinning of malignant potency of hypoxic tumor cells. By comparing transcription profiles of acutely hypoxic versus hypoxia-exposed cells in primary and recurrent GBM, we will test the hypothesis that there exists a hypoxia memory, i.e., hypoxia-exposed cells retaining a set of hypoxia-induced genes that may be linked to survival fitness and tumorigenic potential. In conjunction to the descriptive part of our study, we have also devised a genetic platform to selectively ablate hypoxic population with temporal control to study their contribution to tumor progression in both primary and recurrent GBM. This functional data will provide direct evidence to test the central hypothesis that hypoxia contributes to tumor progression, and more importantly, tumor relapse after treatment. In summary, our innovative study will gain new insights into the link between hypoxia and GBM malignancy, and set the stage for the discovery of new prognostic tools and therapeutics targets to combat GBM.


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: 2024 ( Subtotal = $0 )
2024	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $211,250 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/30/2023	NON-COMPETING CONTINUATION	$21,125
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/22/2022	NON-COMPETING CONTINUATION	$190,125
														Subtotal = $211,250

Issue Date FY: 2022 ( Subtotal = $253,563 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/15/2021	NEW	$253,563
														Subtotal = $253,563

Grand Total All Awards = $464,813

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Tracing Hypoxic State and Hypoxia Memory in Glioblastoma Progression

Award Number: R21NS125700

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2023

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