Dept. of Cell Biology and Neuroscience
W.M. Keck Center for Collaborative Neuroscience
Rutgers University
604 Allison Rd. , Nelson D-251
Piscataway, NJ 08854

Tel: 732-235-5772
Fax: 732-235-4029

mgrumet@rci.rutgers.edu

Laboratory website

One major focus of our laboratory is to study cell adhesion, a fundamental process that is critical for embryo development and maintenance of mature tissues. Cell adhesion molecules (CAMs) are anchored in the surface of cells and can link cells to adjacent cells and to the extracellular scaffold that surrounds cells by binding to specific receptors. In the nervous system, CAMs are important for cell adhesion as well as cell migration; both processes are critical for the formation of intricate neural networks that mediate higher brain function. Our experiments are providing a better understanding of the function of CAMs and they have implications for the design of new strategies to repair damage to the nervous system.

We have isolated a neuronal CAM called Ng-CAM that is expressed at the surface of neurons and is involved in neuron-glia and neuron-neuron adhesion. Cloning of cDNAs encoding Ng-CAM (and its human homologue called L1) indicated that it contains immunoglobulin-like and fibronectin-like domains extracellularly, and has a short cytoplasmic region. A combination of molecular genetic, protein chemical, and cell biological techniques are being used to identify domains in Ng-CAM/L1 and related CAMs (Nr-CAM and neurofascin) that mediate binding to neurons, glial cells, and extracellular ligands including laminin and brain proteoglycans. Functionally active of regions in CAMs are being investigated in vivo using a rat model for spinal cord contusion to verify explore their functions and uses in vivo. Nr-CAM and neurofascin play critical roles in myelination and formation of the node of Ranvier and we have found that fragments of these CAMs inhibit node formation in a culture model of node development. We have prepared Nr-CAM null mice that are viable and are characterizing these mice and cells derived from them to study the functions of Nr-CAM.

A second major focus in the lab is on radial glia cells, which have recently been shown to be neural stem cells. We have isolated radial glial cell clones that can promote neurite growth both in culture and in vivo. Transplantation experiments are assessing the migration patterns of radial glial cells in the uninjured and contused rat spinal cord, and their ability to promote neuroprotection, axonal growth and nerve regeneration. Studies are in progress to understand the mechanisms of action of radial glia/neural stem cells and how they are able to form bridges across spinal cord lesions. Molecular studies are in progress to search for factors responsible for the radial phenotype using molecular biology and microarray gene chip technology. We are also isolating radial glial cells from embryos and embryonic stem cells to analyze their molecular properties and have prepared immortalized cell lines that resemble radial glia. Transplantation experiments are designed to optimize protocols to protect the injured spinal cord from secondary damage and to promote functional recovery.

For complete list: PubMed

Sakurai, T., Lustig, M., Babiarz,J., Furley, A.J.W., Tait, S., Peter J. Brophy, P., Mason, C. A., Grumet, M. (2001) Overlapping Functions of the Cell Adhesion Molecules Nr-CAM and L1 in Cerebellar Development. J Cell Biol 154: 1259-1273.

Lustig, M., Zanazzi, G., Sakurai, T., Blanco, C., Levinson,S. R., Lambert, S., Grumet, M. and Salzer, J. L., (2001) Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier. Current Biology 11: 1-6

Haspel, J., and Grumet, M. (2003) The L1CAM extracellular region: A multi-domain protein with modular and cooperative binding modes Frontiers in Bioscience 8: s1210-1225.

Custer, A.W., Kazarinova-Noyes, K., Sakurai, T., Xu, X., Simon, W., Grumet, M., Shrager, P.(2003) The role of the ankyrin-binding protein Nr-CAM in node of Ranvier formation. J. Neurosci 23: 10032-10039

Roonprapunt, C., Huang, W Grill, R., Friedlander,D., Grumet, M., Chen,,S., Schachner, M and Young, W. (2003) Soluble Cell Adhesion Molecule L1-Fc Promotes Locomotor Recovery in Rats after Spinal Cord Injury. J. Neurotrauma 20: 871-882

Li, H., Babiarz, J., Woodbury, J., Kane-Goldsmith, N., and Grumet, M. (2004) Spatiotemporal Heterogeneity of CNS Radial Glial Cells and Their Transition to Restricted Precursors. Dev. Biol. 271: 225-238.

Hasegawa, K., Chang, Y.-W., Li. H., Berlin, Y. Ikeda, O., Kane-Goldsmith, and Grumet, M. (2005) Embryonic radial glia bridge spinal cord lesions and promote functional recovery following spinal cord injury Exp. Neurol. 193: 394-410