# Immune regulation of spinal cord regeneration

> **NIH NIH K99** · WASHINGTON UNIVERSITY · 2024 · $103,226

## Abstract

PROJECT SUMMARY/ABSTRACT
Spinal cord injury in mammals triggers a cascade of cellular events that lead to the loss of sensory and motor
function caudal to the site of injury. Following spinal cord injury, immune cells, including microglia and
macrophages, infiltrate into the lesion site and become activated. Depleting microglia and macrophages in
mammalian systems has shown both beneficial and detrimental effects post-injury. Identifying the specific
regenerative immune requirements in mammalian systems has proven difficult due to a complex combination of
anti-regenerative barriers. In contrast, zebrafish spontaneously regenerate a fully severed spinal cord and
provide a platform for identifying pathways necessary for spinal cord regeneration. The zebrafish immune system
is conserved with mammals, and therefore provides a unique system to identify pro-regenerative immune
pathways. In preliminary data, I found microglia and macrophages are necessary for functional and anatomical
recovery post-injury, but the pathways directing microglia/macrophage-dependent spinal cord regeneration are
not known. Microglia and macrophages are highly plastic cells, and their gene expression and behavior have
direct implications on functional outcomes following neural injury. This proposal will identify microglia/
macrophage-specific cellular identities, gene expression, and pathways that are necessary for spinal cord
regeneration in the adult zebrafish. First, two of the most important functions of microglia and macrophages
following spinal cord injury are to direct the healing of injured tissue and clear the lesion site of cellular debris.
Aim 1 (K99 Phase) will utilize loss-of-function mutants to define genes upstream of wound healing that are
necessary for re-establishing immune privilege of the spinal cord after injury. Aim 2 (K99/R00 Phase) will move
from the adult zebrafish spinal cord to a human cell culture system to visualize behavior in human iPSC-derived
microglia and test the conservation of pro-regenerative gene function in human cells. Lastly, the origin of immune
cells will dictate their cellular function and effect on regeneration, and the origins of pro-regenerative microglia
and macrophages are unknown. In Aim 3 (R00 Phase), I will perform lineage tracing in the adult zebrafish
regenerating spinal cord to characterize the origin of expanding immune cells post-injury. These Aims are
designed to apply my strengths in zebrafish genetics and regeneration to the new field of neuroimmunology. To
facilitate my ability to carry out these proposed experiments, I have assembled a team of advisors and
collaborators, taking advantage of the vibrant neural injury and neuroimmunology communities at Washington
University School of Medicine. This proposal will generate novel tools and protocols to measure the immune
events during spinal cord regeneration and offers a foundational niche in the spinal cord injury field through
which I can launch a future tenure-tra...

## Key facts

- **NIH application ID:** 10887192
- **Project number:** 1K99NS133484-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Dana Nicole Shaw
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $103,226
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887192

## Citation

> US National Institutes of Health, RePORTER application 10887192, Immune regulation of spinal cord regeneration (1K99NS133484-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10887192. Licensed CC0.

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