Marie Filbin, Distinguished Professor of Biology
Lab Website: http://filbin.bioweb.hunter.cuny.edu
- 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
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.
- Kadoya K, Tsukada S, Lu P, Coppola G, Geschwind D, Filbin MT, Blesch A, Tuszynski MH. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron. 2009 Oct 29;64(2):165-72.
- Deng K, He H, Qiu J, Lorber B, Bryson JB, Filbin MT. Increased synthesis of spermidine as a result of upregulation of arginase I promotes axonal regeneration in culture and in vivo. J Neurosci. 2009 Jul 29;29(30):9545-52.
- Spencer TK, Mellado W, Filbin MT. BDNF activates CaMKIV and PKA in parallel to block MAG-mediated inhibition of neurite outgrowth. Mol Cell Neurosci. 2008 May;38(1):110-6.
- Cao Z, Qiu J, Domeniconi M, Hou J, Bryson JB, Mellado W, Filbin MT. The inhibition site on myelin-associated glycoprotein is within Ig-domain 5 and is distinct from the sialic acid binding site. J Neurosci. 2007 Aug 22;27(34):9146-54.
- Filbin MT. How inflammation promotes regeneration. Nat Neurosci. 2006 Jun;9(6):715-7.
- Domeniconi M, Zampieri N, Spencer T, Hilaire M, Mellado W, Chao MV, Filbin MT. MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor to inhibit neurite outgrowth. Neuron. 2005 Jun 16;46(6):849-55.
- Gao Y, Deng K, Hou J, Bryson JB, Barco A, Nikulina E, Spencer T, Mellado W, Kandel ER, Filbin MT. Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron. 2004 Nov 18;44(4):609-21.
- Pearse DD, Pereira FC, Marcillo AE, Bates ML, Berrocal YA, Filbin MT, Bunge MB. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med. 2004 Jun;10(6):610-6.
- Filbin MT. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci. 2003 Sep;4(9):703-13. Review. Erratum in: Nat Rev Neurosci. 2003 Dec;4(12):1019.
- Cai D, Deng K, Mellado W, Lee J, Ratan RR, Filbin MT. Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitro. Neuron. 2002 Aug 15;35(4):711-9.
- Domeniconi, M., Cao, Z., Spencer, T., Sivasankaran, R., Wang, K., Nikulina, E., Kimura, N., Cai, H., Deng, K., Gao, Y., He, Z., and Filbin, M.T. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron. 2002 Jul 18;35(2):283-90.
- Qiu J, Cai D, Dai H, McAtee M, Hoffman PN, Bregman BS, Filbin MT. Spinal axon regeneration induced by elevation of cyclic AMP. Neuron. 2002 Jun 13;34(6):895-903.
- Cai D, Shen Y, De Bellard M, Tang S, Filbin MT. Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron. 1999 Jan;22(1):89-101.
- Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron. 1994 Sep;13(3):757-67.