Photo of Zhigang He,  PhD

Zhigang He, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2353
Fax: (617) 730-0243

Zhigang He, PhD

Boston Children's Hospital


  • Professor, Neurology, Harvard Medical School


Research Abstract

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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  • Gan W, Dai X, Dai X, Xie J, Yin S, Zhu J, Wang C, Liu Y, Guo J, Wang M, Liu J, Hu J, Quinton RJ, Ganem NJ, Liu P, Asara JM, Pandolfi PP, Yang Y, He Z, Gao G, Wei W. LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control. Nat Cell Biol 2020; 22:246-256. PubMed
  • Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA. Reprogramming to recover youthful epigenetic information and restore vision. Nature 2021; 588:124-129. PubMed
  • Norsworthy MW, Bei F, Kawaguchi R, Wang Q, Tran NM, Li Y, Brommer B, Zhang Y, Wang C, Sanes JR, Coppola G, He Z. Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others. Neuron 2017; 94:1112-1120.e4. PubMed
  • Lu Y, Belin S, He Z. Signaling regulations of neuronal regenerative ability. Curr Opin Neurobiol 2014; 27C:135-42. PubMed
  • O'Donovan KJ, Ma K, Guo H, Wang C, Sun F, Han SB, Kim H, Wong JK, Charron J, Zou H, Son YJ, He Z, Zhong J. B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS. J Exp Med 2014. PubMed
  • Ho PP, Kanter JL, Johnson AM, Srinagesh HK, Chang EJ, Purdy TM, van Haren K, Wikoff WR, Kind T, Khademi M, Matloff LY, Narayana S, Hur EM, Lindstrom TM, He Z, Fiehn O, Olsson T, Han X, Han MH, Steinman L, Robinson WH. Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. Sci Transl Med 2012; 4:137ra73. PubMed
  • Jiang L, Qin X, Zhong X, Liu L, Jiang L, Lu Y, Fan L, He Z, Chen Q. Glycine-induced cytoprotection is mediated by ERK1/2 and AKT in renal cells with ATP depletion. Eur J Cell Biol 2011; 90:333-41. PubMed
  • Park KK, Liu K, Hu Y, Kanter JL, He Z. PTEN/mTOR and axon regeneration. Exp Neurol 2010; 223:45-50. PubMed
  • Ben J, Gao S, Zhu X, Zheng Y, Zhuang Y, Bai H, Xu Y, Ji Y, Sha J, He Z, Chen Q. Glucose-regulated protein 78 inhibits scavenger receptor A-mediated internalization of acetylated low density lipoprotein. J Mol Cell Cardiol 2009; 47:646-55. PubMed
  • Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 2009; 326:592-6. PubMed
  • Park KK,Liu K,Hu Y,Smith PD,Wang C,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; 322:963-6. PubMed
  • Ji B,Case LC,Liu K,Shao Z,Lee X,Yang Z,Wang J,Tian T,Shulga-Morskaya S,Scott M,He Z,Relton JK,Mi S. Assessment of functional recovery and axonal sprouting in oligodendrocyte-myelin glycoprotein (OMgp) null mice after spinal cord injury. Mol Cell Neurosci 2008; 39:258-67. PubMed
  • Harrington AW,Li QM,Tep C,Park JB,He Z,Yoon SO. The role of Kalirin9 in p75/nogo receptor-mediated RhoA activation in cerebellar granule neurons. J Biol Chem 2008; 283:24690-7. PubMed
  • Goh EL,Young JK,Kuwako K,Tessier-Lavigne M,He Z,Griffin JW,Ming GL. beta1-integrin mediates myelin-associated glycoprotein signaling in neuronal growth cones. Mol Brain 2008; 1:10. PubMed
  • Wang J,He Z. NAD and axon degeneration: From the Wlds gene to neurochemistry. Cell Adh Migr 2010; 3:77-87. PubMed