ANIMAL CORE - ABSTRACT The Animal Core is the center?s most active scientific hub for catalyzing research on in vivo genetic and environmental analysis for the pathogenesis of alcoholic liver and pancreatic diseases (ALPD) pursued by investigators within and outside of the center. The core now generates 22 different versions of the models including a newly developed mouse model of alcoholic hepatitis which utilizes a hybrid feeding technique of ad lib consumption of Western diet and intragastric feeding of ethanol diet plus weekly ethanol binge. The core also developed Western alcohol diet-based tumor-promotion models for hepatocellular carcinoma (HCC) and pancreatic adenocarcinoma (PDAC); alcohol- mediated tumorigenesis by orthotopic transplantation of liver tumor-initiated stem cell-like cells (TICs), patient-derived xenograft (PDX) models for HCC or PDAC, and the mouse with humanized liver cells and immune cells to support translational research. During the current cycle, the Core provided 4,075 mouse models to 30 center and 13 non-center investigators, resulting in 85 publications of which 46 are collaborative papers. The Core?s support facilitated 41 grants acquired and 21 applications submitted by the center members, and 21 grants and 8 applications by 22 non-center investigators. In addition, the Core?s tissue sharing program has provided 555 samples to 27 investigators from 19 institutions across the nation to support their respective alcohol research. In the next cycle, the core will pursue the following specific aims to fulfill its mission of serving the nation for promotion of research on ALPD and cirrhosis: 1. To serve as a national resource by provision of 21 different versions of rodent models which recapitulate advanced and clinically relevant pathologic spectra of ALPD and cirrhosis. 2. To have the PDX and humanized mouse models available as widely available services. 3. To support in vivo genetic analysis and cell fate mapping analysis by utilizing genetic models. 4. To promote cell type specific research via close collaboration with the center?s Integrative Liver Cell Core for better elucidation of cell fate regulation underlying ALPD spectra. 5. To render full support to early-stage scientists, including those funded by the Pilot Project Core to maximize their potential for a successful transition to independent investigators. 6. To stimulate collaboration and synergize productivity via shared use of the models and tissues. 7. To continue developing new models of ALPD by combining genetic and environmental risk factors.
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