# Hes1-loss promotes dysregulation of epithelial homeostasis and inflammation in a serrated adenocarcinoma model

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2022 · $406,858

## Abstract

ABSTRACT
Distinct from the conventional adenoma–carcinoma pathway, the “serrated pathway” is a molecular pathway
postulated for a subset of CRCs that develop from some serrated precursor lesions. In addition, inflammation is
a known risk factor for CRC. However, molecular carcinogenic mechanism driving serrated lesion transformation,
which is frequently associated with chronic inflammation, remains an important knowledge gap. Previously we
found that Notch/HES1 expression is lost in most human sessile serrated adenoma and right-sided CRC and is
a ubiquitous marker for IBD-associated serrated lesions and CRC. In addition, Notch/Hes1-loss underlies the
gut pathology of an animal model of colitis-associated CRC featuring serrated-like lesions. In this proposal, we
will use a combination of approaches (organoid culture, molecular and cellular signaling network analysis of
human SSA and serrated CRC, and microbiome deep gene sequencing, etc) and our unique carcinogen-free
animal models to study the mechanism by which HES1-loss disrupts epithelial homeostasis, and defining how
this process cooperates with a pro-tumorigenic cytokine milieu represented by IL1β to promote carcinogenesis.

## Key facts

- **NIH application ID:** 10874937
- **Project number:** 7R01CA222064-06
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Lan Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $406,858
- **Award type:** 7
- **Project period:** 2023-06-24 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874937

## Citation

> US National Institutes of Health, RePORTER application 10874937, Hes1-loss promotes dysregulation of epithelial homeostasis and inflammation in a serrated adenocarcinoma model (7R01CA222064-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10874937. Licensed CC0.

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