Stephen George Waxman MD, PhD
Bridget M. Flaherty Professor of Neurology and Professor of Neurobiology and of Pharmacology; Director, Center for Neuroscience and Regeneration Research
Axons; Electrophysiology; Genes; Ion Channels; Molecular Biology; Multiple Sclerosis; Pain Syndromes; Sodium Channels; Spinal Cord Injury; Stroke
My research program focuses on the application of molecular techniques to the study of neurological diseases, especially spinal cord injury, multiple sclerosis, and neuropathic pain. We are interested in understanding the molecular basis for functional recovery after CNS injury. Our studies on ion channels in impulse conduction in normal, demyelinated, and regenerating nerve fibers use molecular biological, immunoultrastructural, pharmacological, and patch-clamp techniques. We are also investigating the modification of conduction properties by pharmacologically altering ion channel characteristics, an approach that has led to clinical studies in multiple sclerosis and spinal cord injury. Using familial erythromelalgia, a human pain syndrome as a model system, we are studying the role of sodium channels in the regulation of excitability of pain-signaling sensory neurons. We hope that our work will lead to new therapies not only for erythromelalgia but also for multiple sclerosis, spinal cord injury, and related disorders.
Extensive Research Description
My laboratory focuses on functional recovery in diseases of the brain and spinal cord. In particular, we use a spectrum of methods including molecular biology and genetics, cell biology, electrophysiology, computer simulations, molecular modeling etc. to understand how the nervous system responds to injury, and how we can induce functional recovery. Approaching these issues from a molecule- and mechanism-driven standpoint, we have a special interest in spinal cord injury, multiple sclerosis, and neuropathic pain. Our early studies demonstrated the molecular basis for remissions in MS. We have a major interest in the role of ion channels in diseases of the brain and spinal cord. We have demonstrated, for example, that following injury to their axons, spinal sensory neurons turn off some sodium channel genes, while turning others on. This results in the production of different types of sodium channels (with different kinetics and voltage-dependencies) in these neurons, causing them to become hyperexcitability and thereby contributing to neuropathic pain.
We are also interested in hereditary neuropathic pain and have delineated, for the first time, the molecular basis for a hereditary pain syndrome (inherited erythromelalgia; OMIM #133020;#603415). We have identified mutations in ion channel genes that cause painful peripheral neuropathy, and are moving toward pharmacogenomically-guided pain pharmacotherapy.
My laboratory is also examining the role of abnormal sodium channel expression in spinal cord injury (SCI) and multiple sclerosis (MS). Specific projects focus on molecular mechanisms of recovery of conduction along demyelinated axons, and on molecular substrates of axonal degeneration. We are also studying neuroprotection, and have demonstrated that it is possible to pharmacologically protect axons, so they don't degenerate in SCI and MS.