# Core 3: Mouse Models Core (MM Core)

> **NIH NIH P01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2024 · $472,258

## Abstract

PROJECT SUMMARY – Core 3: Mouse Models Core
The Mouse Models Core (MM Core) will provide essential, value-added services in support of all P01 projects.
As all projects propose preclinical experimental therapeutic trials with murine models, such trials will benefit from
expert professional staff where uniform procedures and standardized imaging protocols would enable
comparison of therapeutic regimens across the P01 and ensure reliability, reproducibility, and consistency of all
proposed studies. In support of these goals, the MM Core has three Specific Aims. The First Aim of the MM Core
is to provide orthotopic transplantation services of mouse and human material, which will be used to identify cell
compartment-specific vulnerabilities. The MM Core will transplant mouse and human pancreatic cancer
organoids to enable analyses of intrinsic and acquired resistance, and to test new strategies for overcoming
these challenges that have historically limited long-term therapeutic successes. The MM Core will use orthotopic
transplantation to: 1) determine the ability of HDAC inhibition to synergize with DNA damaging agents, reprogram
fibroblast heterogeneity, and potentiate the response to immunotherapy (Project 1), 2) assess the impact of LIF
and STAT3 loss in the tumor microenvironment on tumor growth (Project 2), and 3) determine the extent to
which CA-19-9 levels affect autophagy (Project 3). The Second Aim of the MM Core is to provide access to
enough tumors generated in the KPC autochthonous model to perform survival studies on the most promising
drug combination regimens identified in each Research Project. The KPC model is challenging, as the mice must
be bred and genotyped, and then animals with tumors must be enrolled at appropriate and reproducible time
points using ultrasound imaging to assess tumor size. The MM Core will enable the KPC model to be used in a
way that benefits from a dedicated staff with expertise in the specialized diagnostic techniques required to enroll
animals harboring tumors between 5-8 mm. This will ensure consistency in the husbandry needed for survival
studies. To minimize the number of animals required, and costs incurred, decisions on which drug combinations
will be used for KPC survival studies will be based on evaluation of all orthotopic transplantation data by the
Project Leads in consultation with the EAB. Drug combinations showing significant survival benefit in the KPC
model will then be evaluated in a second trial to ensure reproducibility. The Third Aim is designed to provide
access to intraductal injection of viral Cre to create pancreas-specific deletions in mice encoding complex allele
combinations. This unique and demanding technique will be optimized by the Core to achieve uniformity and
reproducibility. Among other applications, this procedure will be used extensively in Project 3 to delineate the
role of AMPK and ULK1/2 in tumorigenesis. Taken together, the MM Core will provide reliable, reproducibl...

## Key facts

- **NIH application ID:** 10883584
- **Project number:** 5P01CA265762-02
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Geoffrey Myles Wahl
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $472,258
- **Award type:** 5
- **Project period:** 2023-07-06 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883584

## Citation

> US National Institutes of Health, RePORTER application 10883584, Core 3: Mouse Models Core (MM Core) (5P01CA265762-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10883584. Licensed CC0.

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