Critical for embryo development and maintenance of mature animals, cell adhesion molecules (CAMs) in the nervous system are implicated in cell-to-cell recognition, cell migration, axonal guidance, and neural connection formation. CAMs are plasma membrane receptors that form links between similar or different cells by binding homophilically or heterophilically. Ligands for CAMs include extracellular matrix (ECM) proteins that are secreted by cells. Our laboratory focuses on molecular and cellular mechanisms of cell-to-cell interaction during neural development and in neurological disease. Current projects include: 1) identifying different domains in Ng-CAM and Nr-CAM that mediate binding to neural cells and modulate cell migration and axonal growth; 2) identifying neuronal and astroglial ligands that bind to neuronal CAMs and analyzing their functions during neural development; 3) characterizing cytoskeletal proteins that interact with cytoplasmic domains of CAMs to investigate signal transduction systems; and 4) analyzing expression and function of CAMs and ECM proteins in human brain tumors. We combine molecular, genetic, protein chemical and cell biological techniques to analyze specific molecular regions using functional assays.

We also found that a receptor protein tyrosine phosphatase (RPTPb) that is expressed by glial cells, binds to neuronal CAMs and the ECM protein tenascin. RPTPb is also synthesized by developing glial and glioma cells as a secreted proteoglycan that is a potent inhibitor of neuronal adhesion and neurite growth. New studies are being planned to understand how changes in the expression of different forms of CAMs and their receptors modulate celullar interactions during neural development.