Determinants Driving Myeloid-Facilitated Renewal and Glia Cell-Mediated Maintenance of Myelin

Advisor: Jian Hu, PhD

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. In the following dissertation, I provide two original contributions to the current knowledge of myelin maintenance, wherein I demonstrate that (1) the Peroxisomal Biogenesis Factor 5 (Pex5) is required by myeloid cells 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 (SC) 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 conserved between the PNS and CNS, and (3) revealing that peroxisome homeostasis is critical in myelin damage-responding myeloid cells and that peroxisome-enhancing or restoring measures can be of relevance to boosting beneficial neuroinflammatory responses in disease-associated demyelination.

Advisory Committee:
Jian Hu, PhD, Chair
Changqing Ju, PhD
Hyun Kyoung Lee, PhD
Ilya Levental, PhD
Louise McCullough, MD, PhD
Vihang Narkar, PhD

Attend via Zoom
Meeting ID: 833 7707 9177
Passcode: 096938