# Effect of inhibition of Wnt signaling using small molecules in human limbal epithelial stem cell differentiation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $17,541

## Abstract

PROJECT SUMMARY
Limbal epithelial stem/progenitor cells (LSCs) in the human corneal epithelium are the front line
of defense to maintain transparency of the cornea. Loss or dysfunction of the LSCs leads to
limbal stem cell deficiency (LSCD), which causes pain, inflammation, and loss of corneal
transparency in patients. Cultivated LSCs from a patient’s healthy LSCs can be transplanted into
the diseased cornea to replenish the LSCs, but maintaining sufficient LSCs and preventing LSC
differentiation in culture to allow for a successful transplant remain a major challenge in the
field. We have previously shown that the Wnt co-receptor Frizzled 7 (Fzd7) was preferentially
expressed by the LSCs and its expression was required to maintain the stem cell phenotype of
LSCs. Additionally, canonical and noncanonical Wnt activation operate in an integrated manner
in the LSCs instead of a mutually exclusive manner as we previously thought. In this proposal,
the effect of Wnt inhibition using a novel Wnt small molecule inhibitor that functions as a Fzd7
blocking peptide (Fzd7-P) will be investigated first using a TopFlash assay. The function and
population of cultivated LSCs following Fzd7-P treatment in a dose dependent manner will be
evaluated as described using biomarkers in the parent grant. The proposed project will further
shed light on the mechanism of Wnt signaling in the regulation of LSCs. The results could
inform further development of Wnt small molecules to maximize the population of
undifferentiated LSCs in culture. The knowledge gained from the proposed project will allow
continued improvement of patient-specific LSCD treatment.

## Key facts

- **NIH application ID:** 10627643
- **Project number:** 3R01EY021797-09S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Sophie Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $17,541
- **Award type:** 3
- **Project period:** 2012-09-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10627643

## Citation

> US National Institutes of Health, RePORTER application 10627643, Effect of inhibition of Wnt signaling using small molecules in human limbal epithelial stem cell differentiation (3R01EY021797-09S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10627643. Licensed CC0.

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