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4/11 Neuroimmune and extracellular matrix interactions in alcohol consumption

Award Number: U01AA020912
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/02/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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4/11 Neuroimmune and extracellular matrix interactions in alcohol consumption - Chronic alcohol consumption induces transcriptional changes in genes encoding structural components and regulators of the extracellular matrix (ECM). The molecular mechanisms underlying these alterations and the functional implications of altered ECM gene expression are not well understood in the context of excessive alcohol drinking. We hypothesize that activation of the immune response-related transcription factor STAT3 in astrocytes results in transcriptional changes in genes encoding ECM components, resulting in alterations in ECM structure and function, synaptic changes, and increased ethanol intake. The proposed experiments will address this hypothesis with three specific aims. In Specific Aim 1, we will use an unbiased approach to determine changes in the cortical ECM proteome, or “matrisome” in mice that have chronically consumed ethanol in a binge-like drinking protocol (drinking in the dark) for 6 weeks. Cutting-edge proteomics and glycomics will be performed to quantitatively measure changes in cortical ECM. These results will be compared to changes in ECM-related genes in existing and new INIA transcriptome datasets and the genes analyzed for STAT3 binding motifs in their promoters. In Specific Aim 2, we will determine the role of astrocyte-expressed STAT3 in alcohol consumption by conditionally knocking out Stat3 in astrocytes using floxed Stat3 mice and the astrocyte-specific Cre line, Aldh1l1-CreERT2. Mice will be tested for binge-like ethanol consumption and dependence-induced escalation of ethanol intake. Association of activated STAT3 with gene promoters in the prefrontal cortex will also be determined after chronic binge-like drinking using chromatin immunoprecipitation with an antibody to phosphorylated STAT3, followed by whole-genome DNA sequencing (ChIP-Seq). Finally, we will determine the role of a specific ECM gene and putative STAT3 target, brevican (Bcan) in alcohol consumption, by conditionally knocking out Bcan in astrocytes as described above. We will also reduce the expression of Bcan in the prefrontal cortex of mice using viral-delivered shRNA and measure binge-like ethanol intake. Brevican is localized perisynaptically and regulates synaptic plasticity. To determine if brevican is more highly associated with synapses after chronic ethanol drinking and if synapse structure in the PFC is altered by chronic ethanol, we will perform super-resolution microscopy with brevican antibody and antibodies to excitatory and inhibitory synaptic markers in mice after chronic binge-like drinking. Within each Specific Aim, we will integrate and collaborate with INIA-Neuroimmune and INIA-Stress investigators. The completion of these Specific Aims will contribute to fundamental knowledge of the molecular and cellular mechanisms by which chronic alcohol drinking alters the ECM and potentially provide new cellular targets to reduce excessive alcohol consumption.


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 = $384,244 )
2025	2025	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	000	15	3/4/2025	NON-COMPETING CONTINUATION	$384,244
														Subtotal = $384,244

Issue Date FY: 2024 ( Subtotal = $426,938 )
2024	2024	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	000	14	1/23/2024	NON-COMPETING CONTINUATION	$384,244
2024	2024	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	001	14	5/21/2024	NON-COMPETING CONTINUATION	$42,694
														Subtotal = $426,938

Issue Date FY: 2023 ( Subtotal = $426,938 )
2023	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	004	13	7/6/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	003	13	5/16/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$326,550
2023	2023	VIRGINIA COMMONWEALTH UNIVERSITY	910 WEST FRANKLIN ST	RICHMOND	VA	23284	RICHMOND CITY	USA	Alcohol Research Programs	001	13	12/2/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$426,938
2023	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	002	12	5/16/2023	COMPETING CONTINUATION	-$326,550
2023	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	12	12/2/2022	COMPETING CONTINUATION	$0
														Subtotal = $426,938

Issue Date FY: 2022 ( Subtotal = $439,725 )
2022	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	12	2/10/2022	COMPETING CONTINUATION	$439,725
2022	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	001	12	3/22/2022	COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	003	12	5/17/2022	COMPETING CONTINUATION	$7,301
2022	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	002	11	5/17/2022	NON-COMPETING CONTINUATION	-$7,301
														Subtotal = $439,725

Issue Date FY: 2021 ( Subtotal = $350,781 )
2021	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	001	11	8/16/2021	NON-COMPETING CONTINUATION	$0
2021	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	11	1/15/2021	NON-COMPETING CONTINUATION	$350,781
														Subtotal = $350,781

Issue Date FY: 2020 ( Subtotal = $388,554 )
2020	2020	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	10	1/22/2020	NON-COMPETING CONTINUATION	$388,554
														Subtotal = $388,554

Issue Date FY: 2019 ( Subtotal = $420,512 )
2019	2019	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	9	1/24/2019	NON-COMPETING CONTINUATION	$420,512
														Subtotal = $420,512

Issue Date FY: 2018 ( Subtotal = $382,740 )
2018	2018	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	004	8	9/21/2018	SUPPLEMENT FOR EXPANSION	$31,959
2018	2018	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	002	8	1/29/2018	NON-COMPETING CONTINUATION	$315,702
2018	2018	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	003	8	5/23/2018	NON-COMPETING CONTINUATION	$35,079
2018	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	7	12/18/2017	COMPETING CONTINUATION	$1,214
2018	2016	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	001	6	12/18/2017	SUPPLEMENT FOR EXPANSION	-$1,214
														Subtotal = $382,740

Issue Date FY: 2017 ( Subtotal = $350,781 )
2017	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	003	7	8/2/2017	COMPETING CONTINUATION	-$350,781
2017	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	004	7	8/18/2017	COMPETING CONTINUATION	$350,781
2017	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	002	7	6/7/2017	COMPETING CONTINUATION	$1,018
2017	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	7	2/1/2017	COMPETING CONTINUATION	$350,781
2017	2015	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	001	6	6/7/2017	NON-COMPETING CONTINUATION	-$1,018
														Subtotal = $350,781

Issue Date FY: 2016 ( Subtotal = $105,908 )
2016	2016	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	6	8/19/2016	SUPPLEMENT FOR EXPANSION	$105,908
2016	2015	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	001	6	8/22/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $105,908

Issue Date FY: 2015 ( Subtotal = $254,182 )
2015	2015	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	6	8/13/2015	NON-COMPETING CONTINUATION	$254,182
														Subtotal = $254,182

Issue Date FY: 2014 ( Subtotal = $254,666 )
2014	2014	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	000	5	8/6/2014	NON-COMPETING CONTINUATION	$254,666
														Subtotal = $254,666

Issue Date FY: 2013 ( Subtotal = $231,008 )
2013	2013	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	003	4	8/12/2013	NON-COMPETING CONTINUATION	$244,912
2013	2012	ERNEST GALLO CLINIC & RESEARCH CENTER	5858 HORTON STREET, SUITE 200	EMERYVILLE	CA	94608	ALAMEDA	USA	Alcohol Research Programs	002	2	1/25/2013	NON-COMPETING CONTINUATION	$0
2013	2012	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Alcohol Research Programs	001	3	1/9/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$264,168
2013	2012	ERNEST GALLO CLINIC & RESEARCH CENTER	5858 HORTON STREET, SUITE 200	EMERYVILLE	CA	94608	ALAMEDA	USA	Alcohol Research Programs	000	2	12/19/2012	NON-COMPETING CONTINUATION	-$278,072
														Subtotal = $231,008

Issue Date FY: 2012 ( Subtotal = $278,072 )
2012	2012	ERNEST GALLO CLINIC & RESEARCH CENTER	5858 HORTON STREET, SUITE 200	EMERYVILLE	CA	94608	ALAMEDA	USA	Alcohol Research Programs	000	2	7/24/2012	NON-COMPETING CONTINUATION	$278,072
														Subtotal = $278,072

Issue Date FY: 2011 ( Subtotal = $278,959 ) (Continued on the next page)
Grand Total All Awards = $4,974,008

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4/11 Neuroimmune and extracellular matrix interactions in alcohol consumption

Award Number: U01AA020912

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 11/02/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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