# Exploring Wnt-Fzd signaling specificities

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $205,834

## Abstract

Project Summary
We are requesting funds to purchase a fluorescence-based cell sorter, the BioRad S3E, for the
purpose of screening nanobody libraries and identifying and isolating high affinity binders to cell
surface proteins that transduce Wnt signals.
Wnt proteins represent an important class of developmental signals with diverse functions across
all metazoan species. Deregulation of Wnt signaling can have catastrophic consequences,
including embryonic lethality, birth defects, and disease. Specific and selective targeting of Wnt
signaling has great therapeutic potential in regenerative medicine and the treatment of cancer.
Additionally, with their diverse and potent activities in development and stem cells, Wnt proteins
hold great promise as potent tools in cell and tissue engineering.
The long-term objective of our research is to gain a better understanding of how Wnt proteins and
their downstream signaling events influence cell fate decisions, and thereby advance
technologies and treatments that specifically target Wnt signaling. To this end, we have developed
an innovative technology that utilizes engineered Wnt agonists, called Wnt mimetics, which exhibit
superior biochemical properties compared to native Wnt proteins. Using our previously developed
and published Wnt mimetic, called F7L6, as a guide, we propose to develop a collection of such
Wnt agonists, each designed to engage and activate distinct types of Wnt receptors. The
requested instrument will enable the identification and isolation of novel high affinity binders and
accelerate the development of novel Wnt mimetics.
The proposed research will significantly advance the field of stem cell research and tissue
engineering by establishing new tools and methods to manipulate Wnt signaling in vitro and in
vivo. With its abundant roles in human disorders and diseases, a better understanding of Wnt
signaling is essential for the development of novel therapies for currently incurable diseases.

## Key facts

- **NIH application ID:** 10388751
- **Project number:** 3R35GM134961-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** KARL H WILLERT
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,834
- **Award type:** 3
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388751

## Citation

> US National Institutes of Health, RePORTER application 10388751, Exploring Wnt-Fzd signaling specificities (3R35GM134961-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10388751. Licensed CC0.

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