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Collaborative Activities of the Key Transcription Factors in Glioblastoma Stem-like Cancer Cells

Award Number: SC3GM141756
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Collaborative Activities of the Key Transcription Factors in Glioblastoma Stem-like Cancer Cells - ABSTRACT The median survival time of glioblastoma multiform (GBM) patients is only 15 months from initial diagnosis, making it the most aggressive and lethal form of adult brain tumor. The World Health Organization (WHO) classifies GBM as a grade IV tumor (the highest grade), and only 5% of the GBM patients survive 5 years or longer after diagnosis. The poor prognosis and high mortality rates of GBM are due, in part, to the stem-like tumor-propagating cells present in the GBM. Although these GBM stem-like cancer populations are believed to contribute to therapeutic resistance and cancer recurrence, the underlying mechanism of stem cell induction and maintenance, is not fully understood. The ultimate goals of this proposal are to identify stem- specific genes controlled by two key transcription factors and develop novel DNA methylation technologies to eliminate GBM stem populations. The transcription factors SALL2, SOX2, OLIG2 and POU3F2 are required for reprogramming differentiated GBM cells into stem-like tumor propagating cells. Of these proteins, only SALL2 appears to physically interact with SOX2. This will be the first investigation to evaluate the pathological consequences of the interaction between SALL2 and SOX2, identifying its target genes and determining their roles in driving GBM stem populations (Specific Aim I). In addition, this will be the first experimental approach to precisely target the SALL2 promoter for methylation, blocking its expression and thus eliminating GBM stem-like cancer cells (Specific Aim II). Completion of these aims will substantially increase our understanding of how GBM stem-like cells are induced and maintained. Our innovative approaches will facilitate the development of novel methylation-mediated therapeutics to block therapeutic resistance and inhibit tumor recurrence by specifically suppressing GBM stem-like populations.


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	TEXAS A & M UNIVERSITY KINGSVILLE	700 N UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	4	1/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $103,500 )
2024	2024	TEXAS A & M UNIVERSITY KINGSVILLE	700 N UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	4	3/15/2024	NON-COMPETING CONTINUATION	$93,150
2024	2024	TEXAS A & M UNIVERSITY KINGSVILLE	700 N UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	001	4	6/18/2024	NON-COMPETING CONTINUATION	$10,350
														Subtotal = $103,500

Issue Date FY: 2023 ( Subtotal = $103,500 )
2023	2023	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	3	3/7/2023	NON-COMPETING CONTINUATION	$103,500
														Subtotal = $103,500

Issue Date FY: 2022 ( Subtotal = $103,500 )
2022	2022	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	001	2	6/15/2022	NON-COMPETING CONTINUATION	$10,350
2022	2022	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	2	3/21/2022	NON-COMPETING CONTINUATION	$93,150
														Subtotal = $103,500

Issue Date FY: 2021 ( Subtotal = $103,500 )
2021	2021	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	1	5/1/2021	NEW	$103,500
														Subtotal = $103,500

Grand Total All Awards = $414,000

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Collaborative Activities of the Key Transcription Factors in Glioblastoma Stem-like Cancer Cells

Award Number: SC3GM141756

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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