Saturday, November 23, 2024
11/23/2024
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).
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
