Dissertations and Theses (Open Access)

Author ORCID Identifier

0000-0002-6110-0393

Date of Graduation

5-2026

Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Jian Hu

Committee Member

Louise D. McCullough

Committee Member

Changqing Ju

Committee Member

Hyun Kyoung Lee

Committee Member

Ilya Levental

Committee Member

Vihang Narkar

Abstract

Myelin is a multilamellar sheath that is critical for axonal insulation and metabolic support. Myelin maintenance and turnover is reliant on an intricate balance between myelin synthesis and degradation involving multiple cell types, including myelin-synthesizing glia and myelin-degrading myeloid cells and microglia. In the following dissertation, I provide two original contributions to the current knowledge of myelin maintenance, wherein I demonstrate that (1) peroxin 5 (PEX5) is required by myeloid cells and microglia to enable myelin degradation, particularly in the context of pathological demyelination in the central nervous system (CNS), and that (2) the RNA-binding protein, quaking (QKI), is a constituent of the gene regulatory network driving myelin maintenance in Schwann cells in the adult peripheral nervous system (PNS). The findings reported and discussed here contribute to the field by (1) expanding the small catalog of gene regulatory network components required for PNS myelin maintenance, (2) demonstrating that the dynamics of myelin lipid renewal appear similar between the PNS and CNS, and (3) revealing that peroxisome homeostasis is critical in myelin damage-responding microglia and that peroxisome-enhancing or restoring measures can be of relevance for boosting beneficial neuroinflammatory responses in disease-associated demyelination.

Keywords

myelin, microglia, PEX5, ABCD1, adrenoleukodystrophy, peroxisome, foamy, Schwann, quaking, QKI

Available for download on Wednesday, May 12, 2027

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