Biological Role(s) of Gangliosides

Research interests in this laboratory focus on the biological roles of gangliosides, sialylated glycosphingolipids found in greatest concentration in the gray matter of the brain and, at the level of the cell, on the outer surface of the plasma membrane. While the exact cellular function(s) of these lipids is not known, they can enhance process formation by neuroblastoma cells maintained in vitro, and in vivo they can enhance recovery from certain lesions in the central nervous system. We are interested in how gangliosides given ip or iv cross the blood-brain barrier and in identifying which portion(s) of the lipid is needed to induce specific cellular responses. A second interest of this lab is to utilize the fact that gangliosides can function as ligands for the adherence of certain viruses, bacteria, and bacterial toxins as the starting point for the development of inhibitors of the adherence of such pathogens. Using cholera toxin as a model, we found that we could synthesize multivalent oligosaccharides that inhibited its adherence to cell surface associated GM1, a known ligand. Currently, this approach is being used in studies of botulinum neurotoxin A which adheres to the ganglioside GT1b.