# Genetic and Dietary Interactions in MMR  Deficient Colon Tumorigenesis

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $167,500

## Abstract

A novel mouse model we constructed (villin-cre, Msh2flox/flox, TgfbrII”humanized” ) faithfully recapitulates
mutations and a key genetic circuit driving defective mismatch repair tumorigenesis. In this model we
established feeding a higher risk purified western style diet is necessary to produce tumors in the colon
rather than mainly in the small intestine, therefore completely mimicking interaction of nutritional and
genetic risk factors for human colon cancer.
 Our goals are to: a) use an approach of partial repletion of dietary alterations to identify which
components of the diet impact the development of colon tumors in this VcMshThu model; b) use single
cell RNAseq, now routine in our group, to dissect the dietary induced cellular and transcriptional
remodeling of the colonic mucosa by the multiple diets to determine which aspects of remodeling of the
colonic mucosa by the dietary factors promote tumor development in the colon.
 The data will provide unprecedented understanding of which and how key common dietary
components in the human western style diet of developed countries promote higher risk for colon tumor
development, and the complex cellular and molecular remodeling of the colonic mucosa of the western
diet and components that promote development of these tumors. The translational potential is
development of much deeper understanding of mechanisms establishing risk for CRC, and thus
identification of new early markers of risk. This can inform cost effective strategies for screening and
more efficacious new strategies for intervention.

## Key facts

- **NIH application ID:** 10095460
- **Project number:** 3R01CA222358-04S1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** LEONARD H AUGENLICHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,500
- **Award type:** 3
- **Project period:** 2018-07-05 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10095460

## Citation

> US National Institutes of Health, RePORTER application 10095460, Genetic and Dietary Interactions in MMR  Deficient Colon Tumorigenesis (3R01CA222358-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10095460. Licensed CC0.

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