# Core B-Modeling & Experimental Therapeutics Core

> **NIH NIH P01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $197,102

## Abstract

Core B (Modeling & Experimental Therapeutics Core) - Abstract/Summary
Genetically engineered mouse (GEM) models remain central to virtually all aspects of this P01 and have
contributed significantly to our understanding of both mouse and human pancreatic cancer. GEM models,
particularly those with inducible oncogenes, have enabled (i) elucidation of the role of specific genetic/pathway
alterations in tumor biological mechanisms such as autophagy and immunity, (i) dissection of cooperative
interactions between genetic elements such Kras* and different tumor suppressors such as p16ink4a, p53 and
Smad4, and (iii) deconvolution of the heterotypic interactions across different cell types of the tumor
microenvironment such as Kras* in cancer cells and TGFb in immune cells. In this renewal, two reasons
prompted us to establish this new Core. First, the extreme allelic complexity of the models employed in each
Project will benefit from dedicated sophisticated engineering. Along these lines, it is worth noting that our models
may harbor as many as ten genetic alterations. Core B’s ES-GEM system serves as a powerful platform to
introduce new alleles into existing multi-allelic ES lines harboring core PDAC-relevant alleles. Second, nearly all
aims propose preclinical experimental therapeutic trials with GEM models. Such trials will benefit from expert
execution with professional staff where standardized protocols would enable comparison of therapeutic regimens
across the P01. Here again, the ES-GEM system helps tremendously as it enables highly efficient generation
of large cohorts from one or two rounds of blastocyst injection to produce PDAC-prone mice that can be enlisted
into multi-arm trials. The ES-GEM system has been proven to generate experimental cohorts with all the
characteristics of a germline model. In addition, this approach dramatically reduces time and cost associated
with large breeding colonies for therapeutic experiments.

## Key facts

- **NIH application ID:** 10170994
- **Project number:** 2P01CA117969-16
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** James wesley Horner
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,102
- **Award type:** 2
- **Project period:** 2005-12-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170994

## Citation

> US National Institutes of Health, RePORTER application 10170994, Core B-Modeling & Experimental Therapeutics Core (2P01CA117969-16). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10170994. Licensed CC0.

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