# TRANSCRIPTION FACTORS IN INTESTINAL DIFFERENTIATION AND CANCER

> **NIH NIH K00** · STANFORD UNIVERSITY · 2020 · $97,852

## Abstract

Colorectal cancer (CRC) is one of the most common and lethal cancers worldwide. Under physiological
conditions, the Notch and Wing-less/Int (Wnt) signaling pathways modulate homeostasis and differentiation of
the intestinal epithelium. In intestinal cancers, these pathways are frequently dysregulated. Canonical Wnt/β-
catenin signaling pathway activation, with resultant high β-catenin transcriptional activity, is frequently
implicated in human CRC; however, there are currently no treatments targeting this pathway. Several points of
crosstalk between Notch and Wnt pathways have been described in CRC. Thus, uncovering the molecular
mechanisms of transcriptional networks governed by the Notch and Wnt/β-catenin pathways in intestinal
tumorigenesis is significant for advancing scientific knowledge on cancer biology, and would potentially provide
a window for new CRC therapeutics. The long-term goal of the proposed research is to identify how
transcriptional machinery controls intestinal cell differentiation and how critical transcription factors contribute
to intestinal tumorigenesis. In Aims 1 and 2, using the novel transgenic mouse models and unbiased highthroughput
RNA and DNA sequencing techniques, I have managed several parallel projects and multiinstitutional
collaborations to understand the role of transcription factor Atoh1 (Atonal homolog 1), and its
downstream target, SAM Pointed Domain ETS transcription Factor (SPDEF) in CRCs. The results from the
proposed project are expected to significantly advance our current understanding of transcriptional machinery
in CRCs. To extend my current knowledge and gain deeper insight into the biology of cancer, in Aim 3, I plan
to pursue my postdoctoral studies in the direction of understanding how these extracellular components within
the tumor microenvironment contribute to the program of cancer cell metastasis, a primary cause of cancerrelated
fatality with CRCs, especially how these cells grow, invade, migrate, and resist treatment. Collectively,
this training is customized to give me a comprehensive education in basic science research that will be
extremely in achieving my long-term career goal of becoming an independent cancer researcher.

## Key facts

- **NIH application ID:** 9976474
- **Project number:** 5K00CA212433-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Yuan-Hung Lo
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $97,852
- **Award type:** 5
- **Project period:** 2017-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976474

## Citation

> US National Institutes of Health, RePORTER application 9976474, TRANSCRIPTION FACTORS IN INTESTINAL DIFFERENTIATION AND CANCER (5K00CA212433-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976474. Licensed CC0.

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