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Novel animal models to study miRNA-mediated alcoholic liver disease

Award Number: UH3AA026903
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: 09/26/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Novel animal models to study miRNA-mediated alcoholic liver disease - PROJECT SUMMARY This application is in response to the funding opportunity “Alcoholic hepatitis clinical and translational network – basic and preclinical research (RFA-AA-18-006) under UH2/UH3 funding mechanism”. The goals of our application are to stimulate innovative basic/pre-clinical research to facilitate our understanding on the role of miR-21 in AH. We propose an exploratory yet novel approach to generate animal model targeting cell-type specific miR-21 in the liver. As a proof of concept to support our approach, we have generated hepatocyte specific miR-21-/- mice. Using the loss of function approach, we found, for the first time the connection between miR-21 and lipid metabolism, that hepatocyte miR- 21-/- mice are more sensitive to hepatic steatosis after alcohol feeding. As part of UH2 phase (Yrs 1 and 2), we will further explore the phenotypes of hepatocyte miR-21-/- mice in response to alcohol feeding and also propose to assess the feasibility of creating two new experimental animal models by generating KC-specific and HSC-specific miR-21-/- mice, respectively. As one of the goals of this funding mechanism, our proposal during the UH2 phase will lead to a breakthrough in the development of animal models specifically targeting miR-21 that could have a major impact on AH field. The success of the study during the UH2 phase will lead us to the UH3 validation phase to further explore the in-depth mechanistic study on the role of miR-21 in AH (Yrs 3-5) and to translate the understanding of the basic molecular mechanism by integrating our data into the AH network patient-oriented research setting to further determine the prognostic significance of miR-21 in patients with AH (Yrs 4-5).


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 = -$2,419 )
2025	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	000	5	10/28/2024	NON-COMPETING CONTINUATION	-$2,419
														Subtotal = -$2,419

Issue Date FY: 2022 ( Subtotal = $379,711 )
2022	2022	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	001	5	6/14/2022	NON-COMPETING CONTINUATION	$379,711
2022	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	000	4	3/1/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $379,711

Issue Date FY: 2021 ( Subtotal = $601,798 )
2021	2021	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	002	4	6/15/2021	NON-COMPETING CONTINUATION	$388,103
2021	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	000	3	11/6/2020	EXTENSION WITH OR WITHOUT FUNDS	$213,695
2021	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	001	3	1/22/2021	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $601,798

Issue Date FY: 2020 ( Subtotal = $396,250 )
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	001	3	8/11/2020	EXTENSION WITH OR WITHOUT FUNDS	$0
2020	2020	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Alcohol Research Programs	000	3	8/3/2020	EXTENSION WITH OR WITHOUT FUNDS	$396,250
														Subtotal = $396,250

Grand Total All Awards = $1,375,340

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Novel animal models to study miRNA-mediated alcoholic liver disease

Award Number: UH3AA026903

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: 09/26/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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