Research

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Zhigang  He, PhD, BM

Zhigang He
Research Center:
F.M. Kirby Neurobiology Center
Program:
Neurobiology Program
Department:
Neurology Research
Hospital Title:
Research Associate
Academic Title:
Professor of Neurology and Ophthalmology, Harvard Medical School
Research Focus Area:
Axon regeneration
Contact:
617-919-2353
Contact Via Email
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Research Overview

Restoring lost function after spinal cord injury or other types of CNS injuries is one of the major challenges of contemporary neuroscience.  Functional deficits after such injuries are primarily due to a disruption of axonal connections.  Thus, to restore motor function after injury, what is needed is regeneration of the severed axons of long fiber tracts in order to re-establish the disrupted connections.

In order to repair the damaged supraspinal tracts, the injured neurons first need to recover the capacity for intrinsic growth, initiating regenerative growth.  Sufficient numbers of regenerating axons then have to cross the lesion site and remake functional synapses with neurons in the caudal spinal cord.  Our recent studies have led to the development of novel and effective genetic methods (deletion of PTEN and/or S0CS3) for re-activating neuronal regenerative capacity and thereby allowing for robust regenerative growth after injury, representing a major achievement in the first step of neural repair. 

We are now poised to tackle the remaining major challenges:  How do regenerating axons find the correct pathways to reach their functional targets?  Are the regenerating axons able to form functional synapses?  To what extent could functional recovery be restored by such regeneration-based approaches?  Could other strategies, such as task-specific training, enhance functional recovery after both optic nerve injury and spinal cord injury?  We expect that answering these questions will establish important principles for exploiting regenerative medicine for treating CNS injury and other neurological diseases. 

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.

Dr. He is the director of the Boston Children’s Hospital Viral Core, which aims to provide technological resources to academic investigators interested in the development and use of viral based vectors. The Boston Children’s Hospital Viral Core aims to provide technological resources to academic investigators interested in the development and use of viral based vectors. Currently, we offer custom lentiviral vector production, custom AAV vector production with a variety of serotypes and aliquots of in-stock vector. The Viral Core is located on the 13th floor of the Center for Life Science building.

The Viral Core is under the direction of Dr. Zhigang He and managed by Dr. Chen Wang and technical support staff. - See more at: http://www.childrenshospital.org/research-and-innovation/research-centers/fm-kirby-neurobiology-center/viral-core#sthash.K27fX7N1.dpuf
The Boston Children’s Hospital Viral Core is located on CLS (Center for Life Science) 13th Floor and is aimed to provide technological resources to academic investigators interested in the development and use of viral based vectors. Currently, we offer custom lentiviral vector production, custom AAV vector production with a variety of serotypes and aliquots of in-stock vector.

The Viral Core is under the direction of Dr. Zhigang He and managed by Dr. Chen Wang and technical support staff. - See more at: http://www.childrenshospital.org/research-and-innovation/research-centers/fm-kirby-neurobiology-center/viral-core#sthash.K27fX7N1.dpuf 

Publications

Publications powered by Harvard Catalyst Profiles
  1. He Z, Jin Y. Intrinsic Control of Axon Regeneration. Neuron. 2016 May 4; 90(3):437-51.
  2. Nawabi H, Belin S, Cartoni R, Williams PR, Wang C, Latremolière A, Wang X, Zhu J, Taub DG, Fu X, Yu B, Gu X, Woolf CJ, Liu JS, Gabel CV, Steen JA, He Z. Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms. Neuron. 2015 Nov 18; 88(4):704-19.
  3. Omura T, Omura K, Tedeschi A, Riva P, Painter MW, Rojas L, Martin J, Lisi V, Huebner EA, Latremoliere A, Yin Y, Barrett LB, Singh B, Lee S, Crisman T, Gao F, Li S, Kapur K, Geschwind DH, Kosik KS, Coppola G, He Z, Carmichael ST, Benowitz LI, Costigan M, Woolf CJ. Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS. Neuron. 2015 Jun 3; 86(5):1215-27.
  4. Belin S, Nawabi H, Wang C, Tang S, Latremoliere A, Warren P, Schorle H, Uncu C, Woolf CJ, He Z, Steen JA. Injury-induced decline of intrinsic regenerative ability revealed by quantitative proteomics. Neuron. 2015 May 20; 86(4):1000-14.
  5. Duan X, Qiao M, Bei F, Kim IJ, He Z, Sanes JR. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron. 2015 Mar 18; 85(6):1244-56.
  6. Liu X, Williams PR, He Z. SOCS3: a common target for neuronal protection and axon regeneration after spinal cord injury. Exp Neurol. 2015 Jan; 263:364-7.
  7. Ni Y, Nawabi H, Liu X, Yang L, Miyamichi K, Tedeschi A, Xu B, Wall NR, Callaway EM, He Z. Characterization of long descending premotor propriospinal neurons in the spinal cord. J Neurosci. 2014 Jul 9; 34(28):9404-17.
  8. Lu Y, Belin S, He Z. Signaling regulations of neuronal regenerative ability. Curr Opin Neurobiol. 2014 Aug; 27:135-42.
  9. Belin S, Norsworthy M, He Z. Independent control of aging and axon regeneration. Cell Metab. 2014 Mar 4; 19(3):354-6.
  10. Nawabi H, Zukor K, He Z. No simpler than mammals: axon and dendrite regeneration in Drosophila. Genes Dev. 2012 Jul 15; 26(14):1509-14.
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  12. Zukor K, He Z. Regenerative medicine: drawing breath after spinal injury. Nature. 2011 Jul 14; 475(7355):177-8.
  13. Liu K, Tedeschi A, Park KK, He Z. Neuronal intrinsic mechanisms of axon regeneration. Annu Rev Neurosci. 2011; 34:131-52.
  14. Tedeschi A, He Z. Axon regeneration: electrical silencing is a condition for regrowth. Curr Biol. 2010 Sep 14; 20(17):R713-4.
  15. Park KK, Liu K, Hu Y, Kanter JL, He Z. PTEN/mTOR and axon regeneration. Exp Neurol. 2010 May; 223(1):45-50.
  16. He Z. Intrinsic control of axon regeneration. J Biomed Res. 2010 Jan; 24(1):2-5.
  17. Wang J, He Z. NAD and axon degeneration: from the Wlds gene to neurochemistry. Cell Adh Migr. 2009 Jan-Mar; 3(1):77-87.
  18. Kaneko S, Wang J, Kaneko M, Yiu G, Hurrell JM, Chitnis T, Khoury SJ, He Z. Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J Neurosci. 2006 Sep 20; 26(38):9794-804.
  19. Wang J, Zhai Q, Chen Y, Lin E, Gu W, McBurney MW, He Z. A local mechanism mediates NAD-dependent protection of axon degeneration. J Cell Biol. 2005 Aug 1; 170(3):349-55.
  20. Yiu G, He Z. Signaling mechanisms of the myelin inhibitors of axon regeneration. Curr Opin Neurobiol. 2003 Oct; 13(5):545-51.
  21. He Z, Wang KC, Koprivica V, Ming G, Song HJ. Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system. Sci STKE. 2002 Feb 12; 2002(119):re1.
  22. Wang KC, Kim JA, Sivasankaran R, Segal R, He Z. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature. 2002 Nov 7; 420(6911):74-8.
  23. Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci. 2006 Aug; 7(8):617-27.
  24. Fischer D, He Z, Benowitz LI. Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J Neurosci. 2004 Feb 18; 24(7):1646-51.
  25. 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.
  26. 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 Nov 7; 322(5903):963-6.
  27. Sun F, Park KK, Belin S, Wang D, Lu T, Chen G, Zhang K, Yeung C, Feng G, Yankner BA, He Z. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature. 2011 Nov 06; 480(7377):372-5.
  28. 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.
  29. Hu Y, Park KK, Yang L, Wei X, Yang Q, Cho KS, Thielen P, Lee AH, Cartoni R, Glimcher LH, Chen DF, He Z. Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron. 2012 Feb 9; 73(3):445-52.
  30. He Z, Koprivica V. The Nogo signaling pathway for regeneration block. Annu Rev Neurosci. 2004; 27:341-68.
  31. Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, Neve RL, He Z. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature. 2002 Jun 27; 417(6892):941-4.
  32. Park JB, Yiu G, Kaneko S, Wang J, Chang J, He XL, Garcia KC, He Z. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron. 2005 Feb 3; 45(3):345-51.
  33. Sivasankaran R, Pei J, Wang KC, Zhang YP, Shields CB, Xu XM, He Z. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci. 2004 Mar; 7(3):261-8.
  34. 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 Oct 23; 326(5952):592-6.
  35. 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. 2005 Oct 7; 310(5745):106-10.
  36. Sun F, He Z. Neuronal intrinsic barriers for axon regeneration in the adult CNS. Curr Opin Neurobiol. 2010 Aug; 20(4):510-8.
  37. Zhai Q, Wang J, Kim A, Liu Q, Watts R, Hoopfer E, Mitchison T, Luo L, He Z. Involvement of the ubiquitin-proteasome system in the early stages of wallerian degeneration. Neuron. 2003 Jul 17; 39(2):217-25.
  38. Zukor K, Belin S, Wang C, Keelan N, Wang X, He Z. Short hairpin RNA against PTEN enhances regenerative growth of corticospinal tract axons after spinal cord injury. J Neurosci. 2013 Sep 25; 33(39):15350-61.
  39. Jin D, Liu Y, Sun F, Wang X, Liu X, He Z. Restoration of skilled locomotion by sprouting corticospinal axons induced by co-deletion of PTEN and SOCS3. Nat Commun. 2015 Nov 24; 6:8074.
  40. Bei F, Lee HH, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou L, Hensch TK, Frank E, Sanes JR, Chen C, Fagiolini M, He Z. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-32.
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F.M. Kirby Neurobiology Center

The F.M. Kirby Neurobiology Center, together with the Neurobiology Program at Boston Children’s Hospital, is the largest basic neuroscience research enterprise at a U.S. hospital. It incorporates basic and translational neuroscience research, focusing primarily on developmental neurobiology.

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