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Ethanol Effects on the Transcriptional Regulatory Network in Liver Regeneration

Award Number: R01AA018873
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: 09/30/2009
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Ethanol Effects on the Transcriptional Regulatory Network in Liver Regeneration - PROJECT SUMMARY Liver regeneration is a program with a broad range of applications that is designed to maintain a healthy state of the tissue. When the liver gets exposed to severe damage, there is an active repair response that can use the functional cells and help them expand to the optimal size for that tissue. Many toxins and related treatments are capable of damaging the liver tissue to the point where only a modest quantity of liver function remains. However, under these conditions the liver is uniquely positioned to repair its structure and recover the original tissue mass and it is these processes that help maintain liver function, referred to as Liver Regeneration. The repair process has multiple productive applications. However, it may be derailed by processes such as the heavy consumption of alcoholic beverages and as a result, it is subject to monitoring that may derail its usefulness. Unusually, we recently discovered that exposure of our rats to ethanol in their food will chronically lead to a health crisis upon liver injury only in male rats, whereas female rats did not suffer from this affliction. This finding matched our prior studies that had demonstrated that females are more resistant to some types of alcohol-related injury. Moreover, we have developed a research program in which males are subject to a variety of alcohol-related injuries that females are protected from. These findings are correlated with the individual tests for sensitivity of the liver regeneration process resolved in specific interactions. The Specific Aims are summarized here to enable the recovery of the critical points to identify where the problems are located. These aims include (a) studies to test the hypothesis that ethanol affects the tissue state balance of metabolic compensatory adjustments and proliferation to disrupt the integrate response to PHx, (b) studies to test the hypothesis that interlinked cell state transitions across multiple cell types govern the integrative response to ethanol-mediated disruption in a sex- dependent manner; and (c) studies to identify the renormalization of the ethanol-blocked deficiencies in hepatocyte proliferation by normalizing early phase transcriptional regulatory events; We will bridge between animal models and human ALD in these Aims by evaluating the animal study results across a spectrum of human ALD conditions to identify commonalities and translatable mechanisms of ethanol action and putative targets for intervention.


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 = $586,170 )
2024	2024	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	001	14	7/12/2024	NON-COMPETING CONTINUATION	$586,170
2024	2023	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	13	4/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $586,170

Issue Date FY: 2023 ( Subtotal = $590,511 )
2023	2023	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	002	13	8/15/2023	NON-COMPETING CONTINUATION	$586,170
2023	2022	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	001	12	8/15/2023	NON-COMPETING CONTINUATION	$0
2023	2019	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	10	11/23/2022	NON-COMPETING CONTINUATION	$4,341
														Subtotal = $590,511

Issue Date FY: 2022 ( Subtotal = $586,170 )
2022	2022	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	004	12	8/31/2022	NON-COMPETING CONTINUATION	$586,170
2022	2021	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	003	11	4/13/2022	COMPETING CONTINUATION	$4,341
2022	2021	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	001	11	10/27/2021	COMPETING CONTINUATION	$126,568
2022	2019	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	10	10/27/2021	NON-COMPETING CONTINUATION	-$126,568
2022	2019	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	002	10	4/13/2022	NON-COMPETING CONTINUATION	-$4,341
														Subtotal = $586,170

Issue Date FY: 2021 ( Subtotal = $599,223 )
2021	2021	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	11	8/17/2021	COMPETING CONTINUATION	$599,223
														Subtotal = $599,223

Issue Date FY: 2019 ( Subtotal = $586,862 )
2019	2019	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	10	7/2/2019	NON-COMPETING CONTINUATION	$586,862
														Subtotal = $586,862

Issue Date FY: 2018 ( Subtotal = $587,815 )
2018	2018	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	9	6/13/2018	NON-COMPETING CONTINUATION	$587,815
														Subtotal = $587,815

Issue Date FY: 2017 ( Subtotal = $588,744 )
2017	2017	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	8	6/13/2017	NON-COMPETING CONTINUATION	$588,744
														Subtotal = $588,744

Issue Date FY: 2016 ( Subtotal = $591,316 )
2016	2016	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	001	7	9/15/2016	SUPPLEMENT FOR EXPANSION	$70,000
2016	2016	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	7	6/3/2016	NON-COMPETING CONTINUATION	$521,316
														Subtotal = $591,316

Issue Date FY: 2015 ( Subtotal = $478,391 )
2015	2015	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	6	7/3/2015	COMPETING CONTINUATION	$478,391
														Subtotal = $478,391

Issue Date FY: 2013 ( Subtotal = $608,453 )
2013	2013	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	5	7/30/2013	NON-COMPETING CONTINUATION	$608,453
														Subtotal = $608,453

Issue Date FY: 2012 ( Subtotal = $650,352 )
2012	2012	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	001	4	8/20/2012	SUPPLEMENT FOR EXPANSION	$116,250
2012	2012	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	4	7/13/2012	NON-COMPETING CONTINUATION	$534,102
														Subtotal = $650,352

Issue Date FY: 2011 ( Subtotal = $541,140 )
2011	2011	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	3	8/15/2011	NON-COMPETING CONTINUATION	$535,140
2011	2011	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	001	3	9/19/2011	SUPPLEMENT FOR EXPANSION	$6,000
														Subtotal = $541,140

Issue Date FY: 2010 ( Subtotal = $578,886 )
2010	2010	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	003	2	7/30/2010	NON-COMPETING CONTINUATION	$556,161
2010	2010	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	004	2	9/8/2010	SUPPLEMENT FOR EXPANSION	$15,000
2010	2010	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	001	1	3/15/2010	SUPPLEMENT FOR EXPANSION	$7,725
2010	2009	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	1	2/16/2010	NEW	$0
2010	2009	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	002	1	3/17/2010	NEW	$0
														Subtotal = $578,886

Issue Date FY: 2009 ( Subtotal = $550,261 )
2009	2009	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Alcohol Research Programs	000	1	9/28/2009	NEW	$550,261
														Subtotal = $550,261

Grand Total All Awards = $8,124,294

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Ethanol Effects on the Transcriptional Regulatory Network in Liver Regeneration

Award Number: R01AA018873

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: 09/30/2009

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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