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Role of methylation in ethanol-induced microglial activation

Award Number: R21AA025183
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2017
PERIOD OF PERFORMANCE END DATE: 10/31/2020

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Role of methylation in ethanol-induced microglial activation - Microglia serve as resident immune cells in the brain and are considered key contributors to neuroinflammation, a process that has been implicated in the negative, long-term effects of alcohol on the central nervous system. The molecular mechanisms underlying ethanol-induced microglial activation are still unclear and the role of epigenetic regulation in this process is essentially unknown. Preliminary data generated by our labs indicate that one-carbon metabolism as well as enzymes involved in histone methylation are altered in microglia after acute ethanol exposure. Additionally, we have demonstrated that histone methylation changes occur in vitro and in vivo in microglia after ethanol exposure and knockdown of a specific histone demethylase can affect the pro-inflammatory response of microglia. We hypothesize that methylation is an important epigenetic modification that influences partial activation of microglia after acute ethanol exposure and that indirect “classical” activation mediated by methylation occurs in response to ethanol-induced neuronal damage as a result of chronic exposure. In order to test our hypothesis, we plan to 1) characterize ethanol- induced changes in the microglial histone methylation code in both primary pure cultures of microglia and microglia-neuron co-cultures and 2) determine the functional impact of histone methylation in ethanol-induced microglial activation in mouse models of short- and long-term ethanol exposure. The proposed studies incorporate novel approaches such as activity-based protein profiling, methylation-specific quantitative mass spectrometry and ChIP-Seq in order to carry out these aims. This project will be the first ever comprehensive global-scale analysis of methylation and its regulators, which could determine, at least partly, the epigenetic code related to microglial activation phenotype. Characterization of these ethanol-responsive pathways in microglia could also lead to further insight into the development of novel epigenetic therapies for the treatment of neuroinflammation resulting from long-term alcohol abuse.


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: 2021 ( Subtotal = -$11,273 )
2021	2018	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Alcohol Research Programs	000	2	11/13/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$11,273
														Subtotal = -$11,273

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Alcohol Research Programs	000	2	5/13/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Alcohol Research Programs	001	2	7/8/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$107,817
2019	2017	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Alcohol Research Programs	000	1	7/8/2019	NEW	-$107,817
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $278,000 )
2018	2018	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Alcohol Research Programs	003	2	6/7/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$278,000
2018	2018	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Alcohol Research Programs	002	2	6/5/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$278,000
2018	2018	ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES	106 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Alcohol Research Programs	001	2	5/1/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$278,000
2018	2017	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Alcohol Research Programs	000	1	4/30/2018	NEW	$0
														Subtotal = $278,000

Issue Date FY: 2017 ( Subtotal = $189,368 )
2017	2017	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Alcohol Research Programs	000	1	4/17/2017	NEW	$189,368
														Subtotal = $189,368

Grand Total All Awards = $456,095

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Role of methylation in ethanol-induced microglial activation

Award Number: R21AA025183

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2017

PERIOD OF PERFORMANCE END DATE: 10/31/2020

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