# Southern California Research Center for ALPD and Cirrhosis

> **NIH NIH P50** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $430,973

## Abstract

ANIMAL CORE - ABSTRACT
 The Animal Core is the center’s most active scientific hub for catalyzing in vivo genetic, molecular and
cellular research on the pathogenesis of alcohol-associated liver and pancreatic diseases (ALPD)
pursued by investigators within and outside of the center. The Core now generates 16 different versions
of preclinical models including a mouse model of alcohol-associated hepatitis which utilizes a hybrid
feeding technique of ad lib consumption of solid Western diet and intragastric feeding of ethanol diet plus
weekly ethanol binge. The Core also developed Western alcohol diet (WAD)-based tumor-promotion
models for hepatocellular carcinoma (HCC) and patient-derived HCC xenograft (PDX) model; alcohol
diet-based promotion of pancreatic adenocarcinoma in KrasG12/D mice; and liver tumorigenesis by
orthotopic transplantation of liver tumor-initiated stem cell-like cells (TICs) in immunocompetent C57/Bl6
mice fed alcohol diet. Most recently, the Core has developed a novel humanized HCC mouse model with
humanization of parenchymal and non-parenchymal liver cells and immune cells using fetal liver cells. In
this model, a combination of CRISPR/Cas9-based mutations of ARID1A and CTNNB1 common in
alcohol-associated patient HCC in hepatoblasts and WAD feeding results in a heightened HCC incidence
in FRG (Fah-/-;Rag2-/-;Il2rg-/-) mice, serving as an invaluable tool for studies on gene-environment
interactions and pre-clinical therapeutic testing in a humanized setting. These models developed and
produced by the Core will promote translational research on advanced ALPD and cirrhosis.
 During the current cycle, the Core produced 2,401 model mice to serve 24 center and 16 non-center
investigators, supporting 30 publications, 21 grant acquisitions and 8 applications by the center members
and 6 grants and 7 applications by non-center investigators. In addition, the Core’s Repository Program
has provided 333 samples to 16 investigators from 13 institutions across the nation to support their
research mostly funded by NIAAA.
 In the next cycle, the Animal Core will continue pursuing the following six specific aims to fulfill its
mission of serving the nation to advance ALPD research: 1) to serve as a national resource by provision
of 16+ different versions of rodent models which optimally recapitulate advanced and clinically relevant
pathologic spectra of ALPD; 2) to provide the humanized HCC mouse model as a widely available
service; 3) to support in vivo genetic analysis and cell fate mapping analysis; 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; and 6) to stimulate collaboration and synergize productivity by shared use of...

## Key facts

- **NIH application ID:** 10739247
- **Project number:** 2P50AA011999-26
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** HIDEKAZU TSUKAMOTO
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $430,973
- **Award type:** 2
- **Project period:** 1998-12-31 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10739247

## Citation

> US National Institutes of Health, RePORTER application 10739247, Southern California Research Center for ALPD and Cirrhosis (2P50AA011999-26). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10739247. Licensed CC0.

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