# Multicellular Mechanisms Driving Axon Regeneration

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2021 · $301,398

## Abstract

ABSTRACT
 Permanent disabilities following central nervous system (CNS) injuries result from the failure of injured
axons to re-build functional connections. There are currently no therapies to restore mobility and sensation
following spinal cord injury or vision after optic nerve damage. The poor intrinsic regenerative capacity of
mature CNS neurons is a major contributor to the regeneration failure and remains a major problem in
neurobiology. In contrast, peripheral sensory neurons successfully switch to a regenerative state after axon
injury. The long-term goal of my research program is to understand the multicellular mechanisms by which
injured sensory neurons activate a pro-regenerative program and identify potential targets for future treatment
of CNS injuries.
 Activation of an axon growth program relies in part on the expression of regeneration-associated genes.
Because individual gene based approaches have yielded limited success in axon regeneration, we are
focusing on epigenomic regulations, which affect globally, yet specifically a combination of multiple genes. Our
goal is to uncover how the epigenetic landscape is re-organized in the context of axon injury to enable axon
repair. These studies will incorporate cell-type specific epigenomic analyses to study the transcriptional and
chromatin conformation changes elicited by peripheral and central axon injury. Axon regeneration is not cell
autonomous and is influenced by the environment at the level of the axon injury site and at the level of the cell
soma. We have recently discovered that satellite glial cells, the main type of glial cells in sensory ganglia
respond to axon injury and contribute to the repair process. We propose to use powerful combinations of tools
to pursue an innovative line of research aimed at dissecting the multicellular mechanisms orchestrating axon
regeneration and build upon these findings to improve regeneration in CNS models. To achieve this goal, we
will determine the intrinsic neuronal mechanisms controlling axon regeneration, focusing on epigenomics
studies. We will elucidate the contribution of the microenvironment surrounding neuronal soma to the axon
regeneration process, including satellite glial cells and other non-neuronal cells. To determine if findings made
in the mouse model system are predictive of human physiology, we will determine the molecular profile of
human cells surrounding sensory neurons. Finally we propose to manipulate novel pathways we discover to
improve regeneration in two CNS models, spinal cord injury and optic nerve injury. This proposal will use
powerful combinations of tools to pursue an innovative line of research aimed at dissecting the multicellular
mechanisms orchestrating axon regeneration and build upon these findings to improve regeneration in CNS
models.

## Key facts

- **NIH application ID:** 10238542
- **Project number:** 1R35NS122260-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Valeria Cavalli
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $301,398
- **Award type:** 1
- **Project period:** 2021-05-17 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238542

## Citation

> US National Institutes of Health, RePORTER application 10238542, Multicellular Mechanisms Driving Axon Regeneration (1R35NS122260-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10238542. Licensed CC0.

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