Our Focus
Our research is dedicated to investigating the mechanisms that regulate myelin-forming cell development and function. Myelin is a multilayer lipid membrane structure that ensheaths and insulates axons, allowing for the efficient propagation of action potentials along axons. Myelination is a developmental process that begins around birth and is mainly completed by early adulthood. Nevertheless, over the past decade, it has become increasingly evident that myelin is not a static structure that remains unchanged over the lifetime of the individual. The myelinating cells, oligodendrocytes in the central nervous system (CNS), and Schwann cells in the peripheral nervous system (PNS), contribute to a variety of neurological disorders to a far greater extent than formerly realized. This includes previously unsuspected disease targets, as well as acting as critical participants in protection and repair.
Our first line of inquiry will lay the foundation of our future studies by focusing on the transcriptional control of oligodendrocyte differentiation and CNS myelin formation. The transcriptional network that controls oligodendrocyte differentiation and myelin formation contains only a handful of transcription factors, many of which have been characterized in considerable detail by us and others. Nevertheless, our understanding of this transcriptional network is still lacking. Our studies aim to fill this void and fully characterize this transcriptional network by focusing specifically on the transcription factors zinc finger protein 24 (ZFP24) and Sp7. Previous research has identified ZFP24 and Sp7 as transcription factors that are essential for CNS myelination, however, their roles in oligodendrocyte differentiation and the mechanisms by which they promote CNS myelination remain elusive. In order to investigate ZFP24 and Sp7 we have developed novel mice models that allow us to either ablate or activate transcription factors that are crucial for oligodendrocyte lineage cell development.
Our second line of inquiry will examine the effect of PNS demyelination on sensory neurons. Demyelination of the PNS is, unfortunately, a common cause of pain and misery for patients suffering from PNS neuropathy on the background of type 2 diabetes, chemotherapy-induced neuropathy, and hereditary neuropathies. Therefore, it is of utmost importance that we fully understand the molecular consequences of PNS demyelination on sensory neurons. Our experimental model is the DTA mouse combined with Schwann cells’ specific, inducible, Cre line. In prior experiments, we were able to specifically induce PNS demyelination by genetic ablation of Schwann cells from the PNS of the mature animal, without affecting the CNS or neurons.