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Biosynthetic Metabolic Pathway Regulation of Glioma Growth

Award Number: R01NS104339
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: 12/15/2017
PERIOD OF PERFORMANCE END DATE: 11/30/2023

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Biosynthetic Metabolic Pathway Regulation of Glioma Growth - ABSTRACT Biosynthetic metabolic pathways provide the building blocks required for cell growth and generate important cell signaling molecules, including reactive species. When dysregulated, these pathways can contribute to brain pathologies including brain tumors. We determined that one biosynthetic pathway involving GTP cyclohydrolase I (GCH1) as the rate-limiting step contributes to the growth of brain tumors and is elevated in the neoplastic stem cell subpopulation. In patient sample datasets, increased levels of GCH1 also correlate with poor outcomes. These data suggest the importance of understanding the biological and molecular roles of GCH1. We have therefore proposed to determine if GCH1 is critical for regulating reactive species balance in glioma and maintaining neoplastic stem cell characteristics. Potential novel downstream mediators of GCH1 effects will be validated. Pharmacologic and genetic inhibition of GCH1 will determine if targeting of GCH1 is sufficient to decrease glioma growth alone or in combination with standard of care. We anticipate these studies will determine if GCH1 or another molecule in the same biosynthetic pathway should be a further investigated as a biomarker for either outcome or therapeutic response. We hope that our studies will provide a greater understanding of the mechanisms through which metabolism is altered in brain disease and inform future novel treatment strategies.


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 = -$17,952 )
2024	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/15/2024	NON-COMPETING CONTINUATION	-$17,952
														Subtotal = -$17,952

Issue Date FY: 2022 ( Subtotal = $379,306 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	4/29/2022	NON-COMPETING CONTINUATION	$37,929
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/24/2021	NON-COMPETING CONTINUATION	$341,377
														Subtotal = $379,306

Issue Date FY: 2021 ( Subtotal = $379,306 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/11/2021	NON-COMPETING CONTINUATION	$37,929
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/26/2020	NON-COMPETING CONTINUATION	$341,377
														Subtotal = $379,306

Issue Date FY: 2020 ( Subtotal = $379,306 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	2/11/2020	NON-COMPETING CONTINUATION	$37,929
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/15/2019	NON-COMPETING CONTINUATION	$341,377
														Subtotal = $379,306

Issue Date FY: 2019 ( Subtotal = $379,651 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/4/2018	NON-COMPETING CONTINUATION	$379,651
														Subtotal = $379,651

Issue Date FY: 2018 ( Subtotal = $403,333 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/9/2017	NEW	$403,333
														Subtotal = $403,333

Grand Total All Awards = $1,902,950

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Biosynthetic Metabolic Pathway Regulation of Glioma Growth

Award Number: R01NS104339

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: 12/15/2017

PERIOD OF PERFORMANCE END DATE: 11/30/2023

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