Our laboratory is devoted to research on transcriptional and epigenomic regulation of myelination and pathogenesis/treatment of peripheral neuropathies. We have a long standing interest in the interplay of chromatin structure and gene regulation, and we were the first to develop chromatin immunoprecipitation analysis to identify regulatory elements in myelin-associated genes in vivo. These techniques have been combined with novel genomics tools (ChIP-Seq) to characterize genetic/epigenetic mechanisms of myelin formation and how these mechanisms are altered in disorders affecting myelination. These tools have been applied to study the role of Sox10 and associated transcription factors in myelin gene networks in both the peripheral and central nervous systems, and we have also profiled repressive and active histone modifications in peripheral nerve. In addition, we have also identified how several microRNAs are regulated by Sox10 during Schwann cell development. More recently, we have investigated the role of epigenomic changes in the dynamic reprogramming Schwann cells after nerve injury, as Schwann cells are a major determinant in the ultimate regeneration and remyelination of axons after nerve injury.
Our studies have explored the role of the NuRD complex in Schwann cell development, and we also identified the polycomb pathway as an important regulator of many nerve injury genes.
We are also extending our molecular analyses of gene regulation to the analysis of CNS myelination by oligodendroctyes. These tools were applied to study the comparative role of Sox10 and associated transcription factors in myelin maturation in both the peripheral and central nervous systems, and our genomic studies also helped identify the causative mutant gene in a rat model of hypomyelination, known as taiep.
Our studies also include translational projects as we have been engaged in identifying regulatory elements in the human PMP22 gene, which is duplicated in one of the most common forms of the peripheral neuropathy known as Charcot-Marie-Tooth disease. This type of developmental disability is one of the most common inherited disorders in the nervous system. Our studies have provided novel drug screening assays that are being used to develop novel therapeutic strategies to treat Charcot-Marie-Tooth disease. In addition, our initiatives provide a test case for translational efforts for other gene dosage disorders affecting myelination.