# Development of small-molecule Wnt mimetics for corneal epithelial cell regeneration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $152,821

## Abstract

Project Summary/Abstract for supplement
The goal of the parent funding is to develop small-molecule Wnt mimics to increase the efficiency of expansion
of functional human limbal stem cells (LSCs) or corneal epithelial stem/progenitor cells (CESCs) for
transplantation into humans. The approach of creating Wnt mimics is to link two small molecules that bind to
two Wnt co-receptors, Frizzled and LRP5/6, respectively. During the study, we found that gallic acid and
digallic acid bind to Wnt co-receptor LRP5/6. There are four b-propeller domains in the extracellular domain
of LRP5/6. Wnt molecules bind to the second b-propeller domain, whereas DKK proteins, one group of well-
established Wnt antagonists, target the third b-propeller domain. All four b-propeller domains are structurally
similar, but they are different. Therefore, a small-molecule that binds to the second b-propeller domain with
the highest affinity is a Wnt inhibitor, whereas a small-molecule that binds to the third b-propeller domain with
the highest affinity is an inhibitor of DKK. An inhibitor of inhibitor, the molecule is a Wnt activator. Using
computational and cell biology approaches, we propose to analyze gallic acid-related natural products for
their Wnt inhibition and activation activity. As inappropriate activation of Wnt signaling has been implicated
in cancers and many other human diseases, the study may be helpful in exploring a broad therapeutic
application for gallic acid and related compounds.

## Key facts

- **NIH application ID:** 10287234
- **Project number:** 3R01EY028557-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Sophie Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $152,821
- **Award type:** 3
- **Project period:** 2018-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287234

## Citation

> US National Institutes of Health, RePORTER application 10287234, Development of small-molecule Wnt mimetics for corneal epithelial cell regeneration (3R01EY028557-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10287234. Licensed CC0.

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