Grants Funded

Abstract
People with disruption of the PNS from any cause, such as injury, tumor, or disease, often experience profound functional and psychological sequelae. Our ability to provide treatment to people with peripheral nerve injuries or disease has progressed significantly over recent decades. We remain limited, however, in our ability to help people who have had interruption between the nerve and muscle for longer than 12 to 18 months. Beyond this critical time frame, muscle is unable to be salvaged, a connection between nerve and muscle cannot be reestablished as the neuromuscular junctions (NMJs) are lost, and people may endure permanent paralysis, activity limitations, or deformity.

Movement requires two main components: nerve and muscle, which are studied robustly in attempts to improve our ability to manage peripheral nerve injuries or disease. An integral component of the peripheral nervous system (PNS) is the interface between nerve and muscle, the NMJ. Our nervous systems are composed not only of neurons, but also a diverse group of supporting cells called glia. Without glia, both the central and peripheral nervous systems are unable to function. This study focuses on a particular glial cell type located at the NMJ called the terminal Schwann cell. Terminal Schwann cells contribute to the growth and stability of the NMJ and provide a road map for reinnervation of adjacent injured NMJs. Although glia outnumber neurons, less research effort has been focused on these cells.

Given their location and what little is known about their role at the NMJ, terminal Schwann cells may play a critical role in the ability to maintain NMJs after nerve and muscle have been disrupted. Terminal Schwann cells provide an excellent potential therapeutic target. Very little is known about the roles of these cells, and essentially nothing is known about what genetic factors regulate them. In this study we will use several techniques to isolate terminal Schwann cells and screen the genetic regulators that may be specific to this cell type. The genetic factors that we identify in this work will provide exciting initial progress that may lead to novel therapeutic strategies to promote PNS function, even beyond the currently limited therapeutic window.

Biography
Dr. Alison Snyder-Warwick is an Associate Professor of Surgery in the Division of Plastic and Reconstructive Surgery and Director of the Facial Nerve Institute at Washington University in St. Louis. Dr. Snyder-Warwick completed medical school, a research fellowship in Developmental Biology, and surgical residency training all at Wash U. She then travelled to Toronto, Canada for specialized training in pediatric plastic surgery and pediatric microsurgery at the Hospital for Sick Children. Dr. Snyder-Warwick’s main clinical focus includes pediatric plastic surgery and reconstruction for facial nerve disorders, treatment of facial clefts, reconstruction of brachial plexus birth injuries, gender-affirming surgery, and pediatric and adult microsurgical procedures. Her clinical interests have led to pioneering basic science research investigations involving the terminal Schwann cell, a unique glial cell present at the nerve-muscle interface. Dr. Snyder-Warwick is passionate about helping children and adults with facial paralysis, nerve-related injuries, and facial anomalies and is committed to studying novel techniques of optimizing care for people affected by peripheral nerve pathology and facial differences.