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Functional characterization of an enhancer RNA in cerebral ischemia

Award Number: R01NS115835
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: 09/25/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Functional characterization of an enhancer RNA in cerebral ischemia - Recent studies have reported widespread transcription of mammalian enhancers into noncoding RNA transcripts in a stimulus-dependent manner. Growing evidence shows that these enhancer RNAs (eRNAs) have essential roles in orchestrating higher-order chromatin interactions to facilitate gene expression and phenotypic outcomes during development and disease. As a result, eRNAs are emerging as an important component of the gene regulatory machinery. Due to their very recent discovery, the expression and roles of eRNAs in stroke is virtually unknown. Recently, we applied a combination of genome-wide RNA-seq and genome-wide enhancer mapping using ChIP-seq to identify a number of stroke-induced eRNAs at multiple time-points of reperfusion in the mouse cerebral cortex. Our preliminary data confirmed enhancer activity of the genomic loci encoding the eRNAs, showed that the eRNAs are localized to the chromatin, and revealed an important role for one such eRNA in modulating post-stroke brain damage and gene expression. The molecular interactions, functional mechanisms and sex-dependent effects of eRNAs on the post-stroke pathophysiology are unexplored. In the current project, we build upon our preliminary data to evaluate eRNA functionality in-depth during stroke in the adult mouse cortex. Specific Aim 1 will use a combination of crosslinking-immunoprecipitation, fluorescence in situ hybridization and transcriptional-state analysis to determine the molecular targets of the eRNAs as a function of post-stroke reperfusion time in the mouse cortex. Specific Aim 2 will employ eRNA loss-of-function in vivo followed by cellular, physiological, pathological and neurological analyses to evaluate the role of the eRNA in propagating the post-stroke pathophysiology. Specific Aim 3 will evaluate the molecular targets and pathophysiological effects of the eRNA in the female mouse cortex. Together, this work will illuminate the significance of eRNAs in the cerebral cortex and may reveal novel gene regulatory relationships in stroke. This work will pave the way for future studies exploring the therapeutic manipulation of eRNAs to improve post-stroke outcomes.


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: 2026 ( Subtotal = -$3,364 )
2026	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/30/2026	NON-COMPETING CONTINUATION	-$3,364
														Subtotal = -$3,364

Issue Date FY: 2024 ( Subtotal = $362,537 )
2024	2024	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	8/20/2024	NON-COMPETING CONTINUATION	$362,537
														Subtotal = $362,537

Issue Date FY: 2023 ( Subtotal = $373,749 )
2023	2023	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	9/13/2023	NON-COMPETING CONTINUATION	$373,750
2023	2020	COMMUNITY HOSPITAL GROUP, INC., THE	98 JAMES ST STE 400	EDISON	NJ	08820	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/21/2022	NEW	-$1
														Subtotal = $373,749

Issue Date FY: 2022 ( Subtotal = $373,750 )
2022	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	8/8/2022	NON-COMPETING CONTINUATION	$373,750
2022	2021	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/8/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$127,823
2022	2020	COMMUNITY HOSPITAL GROUP, INC., THE	98 JAMES ST STE 400	EDISON	NJ	08820	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/8/2022	NEW	-$127,823
														Subtotal = $373,750

Issue Date FY: 2021 ( Subtotal = $373,750 )
2021	2021	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/19/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$373,750
2021	2020	COMMUNITY HOSPITAL GROUP, INC., THE	98 JAMES ST STE 400	EDISON	NJ	08820	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/19/2021	NEW	$0
														Subtotal = $373,750

Issue Date FY: 2020 ( Subtotal = $360,250 )
2020	2020	COMMUNITY HOSPITAL GROUP, INC., THE	98 JAMES ST STE 400	EDISON	NJ	08820	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/24/2020	NEW	$360,250
														Subtotal = $360,250

Grand Total All Awards = $1,840,672

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Functional characterization of an enhancer RNA in cerebral ischemia

Award Number: R01NS115835

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: 09/25/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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