William J. Karpus

Research Interests

I have been studying the role of chemokines in experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS) for 21 years and have been using rat and mouse models of MS to understand demyelinating disease pathogenesis for the past 29 years. We have identified key chemokines and receptors in the regulation of T cell and macrophage migration and function using a variety of approaches including neutralizing antibody treatment and mice deficient for select chemokine ligands or receptors. These studies have identified significant roles for a subset of chemokines and chemokine receptors in EAE pathogenesis and point to these factors as potential therapeutic targets for MS. More recently, we have observed a role for Delta Like Ligand-mediated Notch signaling in the regulation of chemokine receptor cell surface expression in the control of T cell migration to the central nervous system (CNS). Additionally, we have considerable experience investigating mechanisms of immunologic tolerance in CNS demyelinating diseases as an approach for antigen-specific therapy. The current project will determine mechanisms of chemokine regulation that control lymphocyte entry into the brain and identify new drug targets for relapsing MS therapy.

Selected Publications