Cell and Developmental Biology University of Michigan

Diseases/Research Topics: Nervous System Regeneration, Spinal Cord Injury, Optic Nerve Injury, Multiple Sclerosis, axon stability, Wallerian degeneration, axon regeneration, axon growth, axon guidance, synaptic plasticity, mouse genetics.

A long standing goal of our research is to understand how neuronal growth and sprouting is regulated in the mammalian nervous system during development, adult neuronal plasticity, and following injury (i.e. spinal cord injury, traumatic brain injury, stroke or multiple sclerosis). We pursue a mouse genetic approach to study the function of different classes of proteins that are known to regulate neuronal growth, including members of the Semaphorin family and their cognate receptors (Neuropilins and Plexins), myelin-associated inhibitors and their receptors. The Nogo Receptors NgR1 and NgR2 have been implicated in regulating acute neuronal responses to the myelin inhibitors Nogo/RTN4, Myelin-Associated Glycoprotein (MAG), and Oligodendrocyte-Myelin Glycoprotein (OMgp). We recently identified a novel function for NgR1 in regulating activity-dependent synaptic strength. Ongoing studies are aimed at understanding the mechanisms of how enhanced neuronal plasticity leads to improved functional outcomes following nervous system injury.

A second line of investigation is focused on mechanisms of axon-glia interaction during nervous system development, adult homeostasis and disease such as Multiple Sclerosis. Myelin-associate glycoprotein (MAG) has axon protective function in vivo, however, the mechanisms of MAG mediated axon protection are poorly understood. We have identified the Nogo receptor family member NgR2 as a high affinity receptor for MAG and we are currently investigating the role of NgR2 in MAG signaling in vivo.

Publications

Representative Publications

• Giger, R.J., Venkatesh, K., Chivatakarn, O., Raiker SJ., Robak L., Hofer T., Lee H., and Rader C. (2008) Mechanisms of CNS myelin inhibition: Evidence for distinct and neuronal cell type specific receptor systems (review Restorative Neurology and Neuroscience, in press).
• Lee H., Raiker SJ., Venkatesh, K., Zhang Y., Lee H., Venkatesh K., Shrager P., Yeh, H., and Giger R.J. (2008) Synaptic Function for the Nogo-66 Receptor NgR1: Regulation of Dendritic Spine Morphology and Activity-Dependent Synaptic Strength. J.Neurosci. 28(11):2753-65
• Chivatakarn, O., Kaneko, S., He, Z., Tessier-Lavigne, M., Giger R.J. (2007) The Nogo-66 receptor NgR1 is required only for the acute growth-cone collapsing but not the chronic growth inhibitory actions of Myelin Inhibitors. J. Neurosci. 27(27):7117-24 (http://www.nature.com/nrn/journal/v8/n8/full/nrn2209.html)
• K. Venkatesh, O. Chivatakarn, S.-S. Sheu, and Giger R.J. (2007) Molecular dissection of the myelin-associated glycoprotein receptor complex reveals cell type–specific mechanisms for neurite outgrowth inhibition J. Cell Biology 177(3):393-399
• Hofer, T., Tangkeangsirisin, W., Kennedy, M.G., Mage, R.G., Raiker, S.J., Venkatesh, K., Lee, H., Giger R.J., Rader, C. (2007) Chimeric rabbit/human Fab and IgG specific for members of the Nogo-66 receptor family selected for species cross-reactivity with an improved phage display vector. J. Immunol. Methods 318, 75-87
• Kornack D.R., and Giger R.J. (2005) Probing microtubule +TIPs: regulation of axon branching. Curr Opin Neurobiol. 15:58-66
• Venkatesh, K., Chivatakarn, O., Lee, H., Joshi, P.S., Kantor, D.B., Newman, B.A., Rose, M., Rader, C., Giger R.J., (2005) The Nogo-66 Receptor Homologue NgR2 is a Sialic Acid-dependent Receptor Selective for Myelin-Associated Glycoprotein. J. Neurosci. 25, 808-822
• Kantor, DB., Chivatakarn, O., Oster, S.F., Inatani, M., Peer, K.L., Hansen, M.J., Flanagan, J.G., Yamaguchi, Y., Sretavan, D.W., Giger R.J., Kolodkin, A.L. (2004) Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans. Neuron 44, 961-975
• Kolodkin, A.L. and R.J. Giger (2002). Fasciclins, Semaphorins, Plexins, and Neuropilins. Wiley Encyclopedia of Molecular Medicine (ISBN 0471374946) pp. 1247-1248, 2255-2257, 2529-2530, and 2883-288