# Laminin Receptors and Signals in Schwann Cells

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $376,510

## Abstract

Peripheral neuropathies are a common cause of disability and have no cure. The extracellular signals
that drive Schwann cell differentiation are important for peripheral nervous system myelination and are
potentially accessible to improve failure in certain human peripheral neuropathies. In previous grant
cycles, my laboratory identified essential Schwann cell signaling pathways that are modulated by
LAMININS in the extracellular matrix. Among them, RAC1, a small-RhoGTPase and YAP and TAZ,
effectors of the HIPPO pathway, are essential for normal Schwann cell development. The proposed
research will characterize how RAC1 and the HIPPO pathway intersect and identify novel components
of these pathways. The novel components include STRIATIN3 and MOB4, members of the STRIPAK
complex that we identified as novel RAC1 interactors, and the atypical cadherin CELSR2, a putative
mediator of Schwann cell-axon interactions. Preliminary data show that STRIATIN3 and CELSR2 may
be important for myelination. Furthermore, this research will identify upstream regulators of the HIPPO
pathway in Schwann cells using unbiased approaches. YAP and TAZ may also modulate human
neuropathies by mediating mechanical signals and by controlling the expression of genes such as
Peripheral Myelin Protein 22 (PMP22), whose altered gene dosage causes 80% of Charcot-Marie-Tooth
disease (CMT) cases. To determine if YAP and TAZ modulate PMP22 expression in the context of
CMT, YAP and TAZ mutants will be crossed with CMT1 models to determine if PMP22 expression and
the consequent phenotypes are modulated. This work will reveal novel fundamental regulators of two
important signaling pathways in Schwann cells. As the function of RAC1 and the HIPPO pathway is
conserved in different cell types, this work will elucidate novel aspects of cell biology, in addition to
myelination, and may reveal ways to modulate signaling pathways relevant in human neuropathies.

## Key facts

- **NIH application ID:** 10784606
- **Project number:** 5R01NS045630-19
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Fraser James Sim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,510
- **Award type:** 5
- **Project period:** 2003-07-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784606

## Citation

> US National Institutes of Health, RePORTER application 10784606, Laminin Receptors and Signals in Schwann Cells (5R01NS045630-19). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10784606. Licensed CC0.

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