Seminar

Deconstructing the essential mechanisms in Schwann cell biology and pathology

Ashwin Woodhoo, PhD

Over the years, it has becoming increasing clear that the differentiated state of mature cells is not a fixed state. Rather these cells retain a surprising degree of plasticity, as shown by enforced cell type conversions achieved by nuclear transfer experiments or exogenous expression of transcription factors. Notably, this ability of a cell to radically change its identity is now emerging as an important process in normal physiology, and in disease states, such as cancer. Our research program is centred on deconstructing the cellular and molecular mechanisms that regulate the plasticity of Schwann cells in normal and disease states. Schwann cells are the main glial cells of the peripheral nervous system (PNS), and form myelin sheaths around large diameter axons, which is critical for rapid impulse conduction. These cells, however, can be readily destabilized, leading to the breakdown of myelin (demyelination) and a subsequent switch in phenotypic states. On the one hand, this remarkable plasticity renders the cells vulnerable to immune assaults or genetic defects seen in demyelinating neuropathies and in PNS tumours. On the other hand, this allows the cells to adaptively respond to injury and convert to cells that support axonal regeneration, forming the cornerstone of nerve repair. This process and its relevance to pathological conditions such as demyelinating neuropathies, cancer and nerve repair have been the primary focus of our research. In this talk, I will provide a brief description of our previous work, in which we identified major signals, including the Notch, ERK and the transcription factor c-Jun, the cellular degradation pathway autophagy, and gene-regulatory mechanisms, including DNA methylation and RNA-binding proteins, that play an essential role in this process. I will then describe our ongoing work on gene-regulatory mechanisms in Schwan cell cancers, microbe-induced demyelination and injury-induced Schwann cell reprogramming. Finally, I will provide a snapshot of our future projects, related to various aspects of Schwann cell biology, including post-translational mechanisms, mechanotransduction, mitochondrial metabolism and retrotransposition, for which we have started to generate exciting preliminary results.