# A large animal model to elucidate the role of LGR5 stem cells in cancer

> **NIH NIH R21** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2021 · $213,180

## Abstract

Project Summary
In the United States, colorectal cancer (CRC) is the 3rd leading cause of cancer death among women and
men combined, with of 1 in 20 people being diagnosed with CRC each year. Yet, understanding factors
controlling disease progression and metastasis has been hampered by the lack of a suitable animal model of
CRC. At present, there is considerable information regarding candidate genes that are mutated in CRC and
contribute to tumor locations, tumor phenotype and patient response to treatment1. While candidate genes
can be studied in mice by use of transgenic lines carrying gain-of-function and loss-of function genetic
modifications, mutations in candidate genes such as Apc, result in lesions in mice that differ from those seem
in humans. As a result, modifications of the traditional transgenic model have been required to advance our
understanding of CRC. In contrast, an analogous APC-/- pig model demonstrates predominantly colon tumors,
which are remarkably similar to the human disease.
We propose to combine the strengths of an existing gene edited LGR5-H2B-GFP pig line with the power of a
Cre-inducible Cas9 system to generate a novel line that will allow a careful dissection both in vivo and in vitro
of the molecular pathways associated with the behavior of LGR5 cells in colon cancer. This proposal will allow
for the generation and the initial in vitro and in vivo validation of the model.
This highly relevant large animal model will greatly improve our understanding of how LGR5 cells behavior is
controlled at the molecular level during oncogenic transformation and will be of great use to develop novel
strategies to treat human colorectal cancer, as well as other cancers.

## Key facts

- **NIH application ID:** 10109811
- **Project number:** 1R21CA256001-01
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Jorge A Piedrahita
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $213,180
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109811

## Citation

> US National Institutes of Health, RePORTER application 10109811, A large animal model to elucidate the role of LGR5 stem cells in cancer (1R21CA256001-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10109811. Licensed CC0.

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