My chief scientific interest is the pathogenesis of peripheral neuropathies. My interest in peripheral nerve began with my Ph.D. thesis, and brought me to Penn’s Department of Neurology, which has a distinguished history in this area. In 1993, I collaborated with Dr. Kurt Fischbeck, then a colleague at Penn, in the discovery that mutations in the gene that encodes the gap junction protein connexin32 cause the X-linked form of Charcot-Marie-Tooth disease (CMT). Thus began one of the main lines of research in his laboratory – elucidating why gap junctions are required components of PNS and glia.
The structure and function of the myelinated axon is another focus. My colleagues and students have illuminated the “molecular architecture” of myelinated axons. The issues here are what molecules form the myelin sheath, and what are their functional roles? The emerging evidence indicates that molecular interactions between axons and myelinating glial cells cause regional specializations in axons that are required for saltatory conduction. Further, because demyelination disrupts these regional specializations, salutatory conduction fails. The goals of this work are to understand the molecular basis for conduction, and restore conduction in demyelinating diseases such as multiple sclerosis.
The diagnosis and treatment of peripheral neuropathies is my clinical interest. I am particularly involved with people who have CMT, and is part of on ongoing effort to identify new genetic causes and to determine the relationships between the genotypes and phenotypes of these patients.