# Defining mechanisms of disease and repair in a viral model of multiple sclerosis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $875,447

## Abstract

Abstract: An important unmet clinical need for patients with the demyelinating disease multiple sclerosis (MS)
is an effective method for promoting remyelination that can ameliorate clinical symptoms associated with
demyelination and restore motor function while limiting immune cell infiltration into the CNS. The long-term
objectives of this research proposal are to i) define how chemokine signaling controls neuroinflammation and
disease progression, ii) assess the effects of chemokine signaling in regulating oligodendrocyte progenitor cell
(OPC) maturation and remyelination, iii) further characterize how engrafted human and mouse neural
progenitor cells enhance axonal integrity, promote remyelination and influence
neuroinflammation/demyelination, iv) define mechanisms by which microglia restrict the severity of
demyelination and influence remyelination. To accomplish these goals, we will use a well-accepted pre-clinical
animal models of MS. For over 20 years, my laboratory has used intracranial infection of susceptible C57BL/6
mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV) as a model of viral-induced
demyelination to study molecular and cellular events controlling neurioinflammation, demyelination, and
remyelination. Proposed experimental procedures that will aid in accomplishing our research goals will include
genetic approaches through generation of mice in which targeted genes are either selectively induced/ablated
to assess effect on disease progression and repair, CRISPR technology to ablate specific target genes in NPC
cultures, single cell and nuclear RNA sequencing on immune cells and resident CNS cells and use of 2-photon
(2P) microscopy to visualize axonal damage/repair and remyelination. Collectively, we believe our
experimental goals outlined in this proposal will provide new insight into the pathogenesis of MS as well as
identify new targets for therapeutic intervention to impede disease progression and promote remyelination.

## Key facts

- **NIH application ID:** 10150119
- **Project number:** 5R35NS116835-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Thomas E Lane
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $875,447
- **Award type:** 5
- **Project period:** 2020-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150119

## Citation

> US National Institutes of Health, RePORTER application 10150119, Defining mechanisms of disease and repair in a viral model of multiple sclerosis (5R35NS116835-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10150119. Licensed CC0.

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