Education
B.Sc., 1978, University of Bath, England
Ph.D., 1981, University of Bath, England
Postdoc., 1982-1984, University of Maryland Medical School
Postdoc. 1984-1986, Johns Hopkins Medical School
Research Interest
Inhibitors of axonal regeneration in the adult nervous system:
The mammalian adult CNS does not regenerate after injury. One of the major obstacles to regeneration is inhibitors of regeneration that are present in myelin. Therefore to encourage axonal regeneration these inhibitors must be identified and neutralized. We identified one of these inhibitors of regeneration as myelin-associated glycoprotein (MAG). We are interested in how MAG exerts its inhibitory effects. We are characterizing the signal transduction cascade is initiated when MAG interacts with a growth cone. In addition, we have shown that MAG is a sialic acid binding protein and have mapped the sialic acid binding site to Arg118 in the extracellular domain of MAG. However, sialic acid binding alone is insufficient to inhibit axonal growth. Consequently we are now mapping the site on MAG responsible for inhibition. Coupled to this line of study we are also adopting a variety of strategies to identify the functional MAG receptor on neurons. Finally, rather than identify and neutralize inhibitors of axonal regeneration in myelin individually we have found that if the neuron’s endogenous levels of cAMP are raised, its intrinsic growth state changes such that inhibitors are all overcome simultaneously. We are now characterizing the signaling involved in this cAMP effect and testing this effect in vivo. In the long term, the results of these investigations may contribute to the treatment of spinal cord injury.
Selected Publications
Filbin, M.T. (2000). Axon regeneration: Vaccinating against spinal cord injury. Curr. Biol. 10:R100-R103.
Qiu, J., Cai, D. and Filbin, M.T. (2000). Inhibitors of regeneration in vivo. Glia, 29:166-174.
Cai, D., Shen, Y., DeBellard, M., Tang, S. and Filbin,M.T. (1999) Prior exposure to neurotrophins blocks inhibition of axonal regneration by MAG and myelin via a cAMP-dependent mechanism. Neuron 22:89-101.
Filbin, M.T. (1999). The benefits of adding insult to injury. Neuron 23:2-4.
DeBellard, M., and Filbin, M.T. (1999) Myelin-associated glycoprotein, MAG, slectively binds several neuronal proteins. J.Neurosci Res. 56:213-218.
Shen, Y.J., DeBellard, M.E., Salzer, J.L., Roder, J. and Filbin, M.T. (1998). Myelin-associated glycoprotein (MAG) in myelin and expressed by Schwann cells inhibits axonal regeneration and branching. Mol. Cell. Neurosci. 12:79-91.
Tang, S., Mukhopadhyay, G., Shen, J., DeBellard, ME, Crocker, P.R. and Filbin, M.T. (1997). Myelin-associated glycoprotein (MAG) interacts with neurons via a silaic acid binding site at Arg118 and a distinct neurite inhibition site. J. Cell Biol. 138:1355-1366.
DeBellard, M.E., Tang, S., Mukhopadhyay, G., Shen Y.J. and Filbin M.T. (1996). Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via a sialoglycoprotein. Mol. Cell. Neursci. 7:89-10.
Mukhopadhyay, G., Doherty, P., Crocker, P., Walsh, F.S. and Filbin, M.T. (1994). A novel role for myelin associated glycoprotein as an inhibitor of axonal regeneration.Neuron 13:757-767
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