Zhigang He, PhD, BM
F.M. Kirby Neurobiology Center
|Hospital Title||Research Associate|
|Academic Title||Professor of Neurology|
300 Longwood Avenue
Boston MA 02115
We are investigating why injured nerve fibers do not regenerate in the adult mammalian central nervous system (CNS). Understanding the molecular mechanisms underlying this complex problem may eventually allow us to develop therapeutic strategies. My laboratory has studied the two sides to this problem: the extrinsic growth inhibitory activity found at lesion sites in the adult CNS, and the reduced intrinsic growth ability of mature CNS axons.
Previous studies suggested that the extrinsic inhibitory activity is principally associated with components of myelin (the fatty coating around many nerve fibers) and molecules in the glial scar at the lesion site. Recent studies from our laboratory and others suggest 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 composed of the Nogo receptor and its two co-receptors p75/TROY. However, blocking these inhibitory activities is not sufficient to allow long-distance axon regeneration for the majority of neurons in the adult.
Our recent studies led to the identification of two signaling pathways (PTEN-regulated and SOCS3-regulated) that are critical for controlling the intrinsic regenerative ability of mature neurons. By using different injury models, we found that robust axon regeneration occurs after deletion of PTEN or SOCS3, establishing the first set of genetic models with CNS axon regeneration. Our current studies are investigating whether and how these regenerating axons mediate functional recovery after both optic nerve injury and spinal cord injury.
About Zhigang He
Zhigang He received his PhD from the University of Toronto and was a postdoctoral fellow with Marc Tessier-Lavigne at the University of California, San Francisco. He has the honor of being named a Klingenstein Fellow in Neuroscience, a John Merck Scholar and a McKnight Scholar.
Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B, He Z. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 2010 Sep; 13(9):1075-81.
Smith PD, Sun F, Park KK, Cai B, Wang C, Kuwako K, Martinez-Carrasco I, Connolly L, He Z. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 2009 Dec 10; 64(5):617-23.
- Park K, Liu K, Hu Y, Smith P, Chen W, Cai B, Xu B, Connolly L, Kramvis I, Sahin M, He Z. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTor pathway. Science 2008 Nov 7; 322(5903):963-6.
For a list of Zhigang He's publications on PubMed, click here.