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Zhigang He, Ph.D., B.M.

Associate Professor of Neurology

Children's Hospital
Enders 379
300 Longwood Ave
Boston, MA 02115
Telephone: 617 919-2353
Fax: 617- 730-0243
Email: zhigang.he@childrens.harvard.edu
Predocs: 1 Postdocs: 10 Completed PhD's: 4

Zhigang He

We are interested in understanding the cellular and molecular mechanisms involved in axon degeneration and regeneration.

Axon Regeneration

Failure of successful axon regeneration in the CNS is attributed not only to the intrinsic regenerative incompetence of mature neurons, but also to the environment encountered by injured axons. We are interested in exploring the mechanisms for both environmental inhibitory influences and intrinsic regenerative capacity. 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 our 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. Our current studies are aimed to define signaling pathways that transduce these inhibitory signals to cytoskeleton. In addition, we are also actively studying the cellular and molecular mechanisms underlying the intrinsic regenerative capacity of mature neurons. All of these studies are carried out in a combination of in vitro and in vivo approaches.

Axon Degeneration

Axon degeneration occurs frequently in physiological neuronal remodeling and pathological neurodegeneration. We have been using Wallerian degeneration as a model to explore the cellular and molecular mechanisms of axon degeneration. It is hoped that this line of study will provide insights into the mechanisms of brain aging and neurodegenerative diseases.

 

References:

  • 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. 2006 (in press).