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Department
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Neurology
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Hospital Title
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Research Associate
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Academic Title
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Associate Professor of Neurology
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Phone
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617-919-2353
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Fax
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617-730-0243
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Email
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Zhigang He
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Location
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300 Longwood Avenue
Enders-379
Boston MA 02115
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Zhigang He is interested in why lesioned axons cannot regenerate in the adult mammalian central nervous system (CNS). His research has been focused on two potential mechanisms: the inhibitory activity in the adult lesion sites and reduced intrinsic ability associated with mature CNS neurons.
Previous studies indicate that the inhibitory activity is principally associated with components of CNS myelin and molecules in the glial scar at the lesion site. Recent studies from He's laboratory and others suggested that three myelin proteins -- myelin-associated glycoprotein (MAG), Nogo-A and oligodendrocyte myelin glycoprotein (OMgp) -- collectively account for the majority of the inhibitory activity in CNS myelin. The inhibitory activity of MAG, OMgp and the extracellular domain of Nogo-A might be mediated by a receptor complex with a Nogo receptor and at least two co-receptors, p75/TROY and Lingo-1. Blocking such inhibitory activity by genetic and pharmacological approaches could promote local axonal sprouting and reactivate structural plasticity but is not sufficient to allow long-distance axon regeneration.
Our current studies are aimed to define cellular and molecular mechanisms underlying the intrinsic regenerative capacity of mature neurons. He and his colleagues envision two main possibilities for the lack of axon re-growth responses after an injury: (1) the signals carrying information of axotomy fail to reach to the cell body for activating regenerative program; and/or (2) the axonal growth program could not to be reactivated even if the retrograde signals are delivered to the cell bodies. They are addressing these issues by a combination of in vitro and in vivo approaches.
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Zhigang He received his PhD from the University of Toronto and was a postdoctoral fellow with Dr. Marc Tessier-lavigne at UCSF. Dr. He was a Klingenstein Fellow in Neuroscience, John Merck Scholar, and McKnight Scholar.
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- Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, Neve RL, He Z. (2002). Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417, 941-944.
- Wang KC, Kim JA, Sivasankaran R, Segal R, He Z. (2002). P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature Nov 7;420:74-78.
- Park, J, Yiu, G, Kaneko, S, Wang, J, Chang, J, and He, Z. A TNF receptor family member TROY is a co-receptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 45, 345-351, 2005.
- Wang, J, Zhai, Q, Chen, Y, and He, Z. Mediation of NAD-dependent axon degeneration protection by a local mechanism. J Cell Biol 170, 349-355, 2005.
- Koprivica V, Cho KS, Park JB, Yiu G, Atwal J, Gore B, Kim JA, Lin E, Tessier-Lavigne M, Chen DF, He Z. EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans. Science. 310, 106-110, 2005
- Yiu . G. and He, Z. glial inhibitors in axon regeneration. Nature Review Neurosci. 7, 617-627, 2006.
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