Our laboratory is focused on the transcriptional and epigenetic regulation of myelination. Myelin is a vital constituent of the nervous system that increases the speed of action potentials, and also provides trophic support for the long axons that project from neurons. Our studies are centered on the myelin-producing cells of the peripheral nervous system, and the picture below shows a Schwann cell that has synthesized a myelin sheath around the axon to the left. We have focused on elucidating gene regulation of individual myelin genes by two major regulators of Schwann cell function: Egr2 and Sox10. Sox10 is required at virtually all phases of Schwann cell development and Egr2 is required for initation of myelination. For example, we have recently characterized enhancers within the Pmp22 gene, which is duplicated in the most common form of Charcot-Marie-Tooth Disease, classified as CMT1A. These studies are also developing novel screening assays to identify drugs that could be used for this very common peripheral neuropathy.
On a more global level, we are utilizing studies of the NuRD chromatin remodeling complex and miRNA profiling to characterize the epigenetic mechanisms involved in Schwann cell myelination. These studies are integrated with genome-wide analysis of transcription factor distribution (using ChIP-Seq) to develop an interactive map of the genomic programming that is required for myelination by Schwann cells.