# WNT Mediated Induction of Schwann Cell Plasticity

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $210,600

## Abstract

PROJECT SUMMARY
Disorders of the peripheral nervous system, particularly those that affect motor function and pain sensitivity are
major clinical challenges. Current medications are not curative and only address secondary symptoms of
disease. To restore peripheral nerve function after injury, Schwann cells adapt to counteract pathological insults
by undergoing a dramatic transformation to generate repair cells. This complex process, termed
transdifferentiation, requires coordination between multiple signaling and gene regulation programs. During
transdifferentiation Schwann cell myelination, metabolism, adhesion, phagocytic properties and the ability to
activate the immune system are adapted to preserve neuronal survival and function. Transcriptional studies of
nerve injury models have revealed that several canonical signaling pathways are altered after injury, including:
NF-kB, Ras, TGFβ, WNT, and MAPK. Despite the clear upregulation of WNT signaling components, how WNT
signaling contributes to the generation of the repair cell is unclear. Poor understanding of the molecular systems
controlling repair cell formation and function is a critical barrier towards identifying therapeutic targets to treat
nerve injury. We now have the genetic, sequencing and viral tools to dissect how signaling pathways individually
contribute to each of the hallmark repair cell phenotypes. We hypothesize that WNT signaling mediates repair
cell formation by promoting transdifferentiation and the epithelial-to-mesenchymal transition of repair cells. This
grant will 1) provide functional tests of the role of WNT receptors and ligands in the control of repair cell formation
2) determine whether reduction of a WNT antagonist can restore peripheral nerve regeneration after injury. To
accomplish these goals, I will leverage my training in disease models of peripheral neuropathy to gain experience
in four critical areas: (1) viral vector design of CRISPR/Cas9 tools, and (2) RNA detection and quantification
techniques, (3) mechanisms of cellular reprogramming, and (4) professional development. To achieve these
training goals, I have assembled an exceptional group of mentors and scientific advisors with specialties in
understanding the roles that glia play during development, injury and neurodegeneration, virus-mediated
CRISPR/Cas9 delivery, and transcriptomics of myelinated tissues. With expert guidance from this group, the
proposed experiments will address the cellular mechanisms of repair cell induction. The results from this
application will serve as the basis for an R01 application to dissect how WNT signaling components orchestrate
the changes in transcription required to reprogram mature Schwann cells into repair cells and test whether WNT
intersects with other relevant intracellular pathways (e.g. MAPK, ERK) during Schwann cell reprogramming.
.

## Key facts

- **NIH application ID:** 10985353
- **Project number:** 1K01NS134780-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Lydia Daboussi
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,600
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985353

## Citation

> US National Institutes of Health, RePORTER application 10985353, WNT Mediated Induction of Schwann Cell Plasticity (1K01NS134780-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10985353. Licensed CC0.

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