# The role of a pair of MAP3Ks in the multicellular response to spinal cord injury

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $96,897

## Abstract

PROJECT SUMMARY / ABSTRACT
After spinal cord injury, a plethora of cellular responses impact functional recovery. Neurons may be preserved
or undergo cell death, axon degeneration and/or regenerative attempt. Astrocytes may become hypertrophic,
seal off the injury epicenter and influence axonal response in complex ways. Other cell types such as
fibroblasts/pericytes, microglia, macrophages also play important roles. Understanding how different cell types
respond to injury, how their responses are regulated and how they contribute to functional recovery is critical
for developing therapeutic intervention to promote functional repair after spinal cord injury. Regeneration is
axonal growth from injured neurons and sprouting is axonal growth from uninjured neurons. Both may
contribute to functional recovery. DLK and LZK are mammalian homologues of invertebrate DLK that has been
shown to play important roles in axon regeneration in C. elegans and Drosophila. The role of mammalian DLK
and LZK in spinal cord repair in not known. In the process of studying DLK (MAP3K12) and LZK (MAP3K13) in
axonal repair after spinal cord injury, our lab has identified a critical role for LZK in astrocytic scarring. This
result corroborates with published literature on Stat3 and Pten to illustrate an emerging theme that signaling
pathways regulating axonal repair may also regulate astrocyte response to injury. In this supplement proposal,
we will investigate the astrocyte specific roles of LZK in spinal cord injury and repair using an array of inducible
loss and gain of function mouse genetic lines. We will map the interaction of LZK with another known signaling
pathway involving Stat3 in regulating astrocyte response, determine the transcriptomic changes and functional
consequences of manipulating these pathways. Together, these studies will contribute to the understanding of
how the astrocyte response is regulated and how it contributes to repair and recovery in both a direct and
indirect manner, the latter through the effect on axonal repair. Such understanding will pave the way for
therapeutic development targeting these molecules to promote repair and recovery after spinal cord injury.

## Key facts

- **NIH application ID:** 10165174
- **Project number:** 3R01NS093055-06S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Binhai Zheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $96,897
- **Award type:** 3
- **Project period:** 2015-05-01 → 2020-08-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165174

## Citation

> US National Institutes of Health, RePORTER application 10165174, The role of a pair of MAP3Ks in the multicellular response to spinal cord injury (3R01NS093055-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165174. Licensed CC0.

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