We explore the molecular mechanisms neural cells use to communicate with each other when they come into contact. This type of communication, Cell-Cell Recognition, is important to nervous system development, and the maintenance of proper intercellular contacts in the adult brain.

Cell-cell recognition occurs when complementary molecules on apposing cell surfaces meet. A receptor on one cell surface binds to its specific ligand on a nearby cell, initiating a cascade of events which regulate cell behaviors ranging from simple adhesion to complex cellular differentiation.

Complex carbohydrates, consisting of glycoproteins and glycolipids, decorate all cell surfaces, and represent the most prominent class of cell surface molecules. Members of this large and highly varied family act as ligands for complementary binding proteins, called lectins, on nearby cells. Lectin-carbohydrate interactions mediate intercellular communication in cell-cell recognition systems in the brain and elsewhere. The study of cell surface complex carbohydrates, lectins, and their roles in cell physiology are part of the rapidly emerging discipline called Glycobiology.

Current work in our laboratory focuses on Neuroglycobiology. Neural cells are rich in a sub-class of cell surface complex carbohydrates called Gangliosides. We discovered that major members of the ganglioside family are ligands for an important cell recognition protein called "Myelin-Associated Glycoprotein," or MAG. We demonstrated that MAG binds to gangliosides on nerve cells to initiate cell-cell recognition which is important for the long-term maintenance of Myelin, the essential insulation surrounding nerve cell axons. Myelin loss results in diseases such as multiple sclerosis. We have also shown that MAG-ganglioside interactions block Axon Regeneration after nervous system disease or injury, including spinal cord injury. A molecular understanding of these interactions may provide new ways to intervene and enhance recovery.

Inflammation is initiated when circulating leukocytes bind to endothelial cells lining the blood vessel wall. This first step in inflammation is mediated by lectins called "selectins" on the endothelium which bind to specific sugars on the leukocyte cell surface. Unique gangliosides bearing sialic acid and fucose residues may be major determinants for selectin-mediated adhesion of human neutrophils and eosinophils. In collaboration with Drs. Bruce Bochner and Kostas Konstantopoulos we are isolating adhesion-supporting gangliosides from human neutrophils and eosinophils, determining their functions using flow chamber rolling assays in vitro, and analyzing their structures using mass spectrometry and other analytical tools. Defining the endogenous glycoconjugates which mediate inflammation may provide new ways to control inflammation.