# Differential Wnt Dependencies in Colon Epithelium.

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $196,204

## Abstract

Project Summary/Abstract
This proposal details a five-year training plan for the development of a research program focused on
elucidating the therapeutic potential of superimposed additional Wnt signaling on colonic neoplasia.
The molecular driver shared across the vast majority of colonic neoplasms is constitutive Wnt
signaling, most commonly caused by loss of function mutations in the APC gene. The loss of function
of APC permits beta catenin to constitutively translocate to the nucleus and induce the formation of
colonic adenomas which can further mutate into colon cancer. To date, strategies to inhibit Wnt
signaling for therapeutic purposes have failed. However, other elements of the beta catenin
destruction complex that work with APC, such as GSK3 alpha and beta can be pharmacologically
inhibited. Therefore, instead of inhibiting Wnt signaling, and informed by the concept that a “just right”
amount of Wnt signaling may be selected for in tumor cells, we hypothesized additional Wnt signaling
would be deleterious to tumor cells but would simultaneously enhance the function of normal cells.
This project will elucidate fundamental dependencies of Wnt signaling in normal tissues as well as
tumors. Ultimately, I believe this will engender a specific therapy for adenomas, to which there is no
existing medical therapy other than polypectomy, and additionally provide a broadly applicable and
potentially safe approach to treat colorectal cancer.
I am clinically trained pathologist and physician scientist seeking K08 support for mentored research.
This work will be mentored by Prof. Omer Yilmaz and Prof. Robert Langer. Prof. Yilmaz is a
pathologist and physician-scientist, and studies the effects of diet on intestinal stem cells and state-
of-the-art intestinal organoid models. Prof. Langer has fundamentally transformed and defined
biomedical engineering, is the most cited engineer in history, and most recently his expertise in
nanoparticle delivery provided the foundation for the Moderna COVID-19 vaccine. The work will be
conducted at the Massachusetts Institute of Technology and Massachusetts General Hospital, both
world class institutions of the highest caliber. I have assembled a scientific advisory committee
consisting of world class cancer biologists to help guide my scientific progress, consisting of Prof.
Tyler Jacks, Prof. Michael Yaffe, and Prof. William Kaelin. This K08 mentored research award will
ensure I have the time and resources to develop expertise in cancer biology and explore this
promising therapeutic and biologically intriguing concept of increased Wnt signaling to specifically
treat colonic neoplasia. This topic will provide ample substrate for me to grow as an independent
physician scientist.

## Key facts

- **NIH application ID:** 10912792
- **Project number:** 5K08CA277011-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** GEORGE ENG
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,204
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912792

## Citation

> US National Institutes of Health, RePORTER application 10912792, Differential Wnt Dependencies in Colon Epithelium. (5K08CA277011-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10912792. Licensed CC0.

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