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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $370,125

## 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. In the past, our lab
has mostly focused on the molecular control of neuronal responses to injury, and in particular axon
regeneration and sprouting following CNS 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, we have 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 proposal, we will comprehensively investigate the
neuron and astrocyte specific roles of LZK and DLK in the multicellular response to spinal cord injury using an
array of inducible loss and gain of function mouse genetic lines. Downstream effectors of DLK and LZK will be
identified through transcriptomic analyses in neurons and astrocytes. Functional synergies or redundancies will
be tested between DLK and LZK, and the interaction with other signaling pathways including Stat3 and Pten
will be tested as well. Together, these studies will determine the contribution of DLK and LZK in axonal repair
and astrocyte response after spinal cord injury, which may pave the way for therapeutic development targeting
these molecules to promote repair and recovery after spinal cord injury.

## Key facts

- **NIH application ID:** 9981399
- **Project number:** 2R01NS093055-06
- **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:** $370,125
- **Award type:** 2
- **Project period:** 2015-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981399

## Citation

> US National Institutes of Health, RePORTER application 9981399, The role of a pair of MAP3Ks in the multicellular response to spinal cord injury (2R01NS093055-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9981399. Licensed CC0.

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