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Intellectual and Developmental Disabilities Research Center Research
Neurology Research

Research Overview

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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. 

Research Background

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. In 2019 Dr. He received the Reeve-Irvine Research Medal.

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.

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Researcher Profile

Meet Zhigang He, PhD, BM

Publications

  1. Imaging Demyelinated Axons After Spinal Cord Injuries with PET Tracer [18F]3F4AP. J Nucl Med. 2025 Jan 16. View Abstract
  2. Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone. Cell. 2024 Jun 20; 187(13):3427-3444.e21. View Abstract
  3. The secondary somatosensory cortex gates mechanical and heat sensitivity. Nat Commun. 2024 Feb 12; 15(1):1289. View Abstract
  4. A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons. Nature. 2023 Dec; 624(7991):403-414. View Abstract
  5. Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye. Proc Natl Acad Sci U S A. 2023 08 22; 120(34):e2306153120. View Abstract
  6. The Secondary Somatosensory Cortex Gates Mechanical and Thermal Sensitivity. Res Sq. 2023 Jun 28. View Abstract
  7. Transcriptomic Analysis of the Ocular Posterior Segment Completes a Cell Atlas of the Human Eye. bioRxiv. 2023 Apr 27. View Abstract
  8. Temporal single-cell atlas of non-neuronal retinal cells reveals dynamic, coordinated multicellular responses to central nervous system injury. Nat Immunol. 2023 04; 24(4):700-713. View Abstract
  9. Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells. Neuron. 2022 08 17; 110(16):2607-2624.e8. View Abstract
  10. Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells. Neuron. 2022 08 17; 110(16):2625-2645.e7. View Abstract
  11. Axon Regeneration: A Subcellular Extension in Multiple Dimensions. Cold Spring Harb Perspect Biol. 2022 03 01; 14(3). View Abstract
  12. Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy. Neuron. 2022 05 04; 110(9):1516-1531.e9. View Abstract
  13. Utilizing mouse optic nerve crush to examine CNS remyelination. STAR Protoc. 2021 09 17; 2(3):100796. View Abstract
  14. Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury. Nat Commun. 2021 02 03; 12(1):781. View Abstract
  15. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020 12; 588(7836):124-129. View Abstract
  16. Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia. Neuron. 2020 12 09; 108(5):876-886.e4. View Abstract
  17. Microglia-organized scar-free spinal cord repair in neonatal mice. Nature. 2020 11; 587(7835):613-618. View Abstract
  18. LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control. Nat Cell Biol. 2020 02; 22(2):246-256. View Abstract
  19. Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes. Neuron. 2019 12 18; 104(6):1039-1055.e12. View Abstract
  20. Elevating Growth Factor Responsiveness and Axon Regeneration by Modulating Presynaptic Inputs. Neuron. 2019 07 03; 103(1):39-51.e5. View Abstract
  21. Touch and tactile neuropathic pain sensitivity are set by corticospinal projections. Nature. 2018 09; 561(7724):547-550. View Abstract
  22. Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2 Manipulations. Cell. 2018 07 26; 174(3):521-535.e13. View Abstract
  23. Deconstruction of Corticospinal Circuits for Goal-Directed Motor Skills. Cell. 2017 Oct 05; 171(2):440-455.e14. View Abstract
  24. A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity. PLoS One. 2017; 12(9):e0184672. View Abstract
  25. A Sensitized IGF1 Treatment Restores Corticospinal Axon-Dependent Functions. Neuron. 2017 Aug 16; 95(4):817-833.e4. View Abstract
  26. Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others. Neuron. 2017 Jun 21; 94(6):1112-1120.e4. View Abstract
  27. The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration. Neuron. 2016 Dec 21; 92(6):1294-1307. View Abstract
  28. Building bridges to regenerate axons. Science. 2016 11 04; 354(6312):544-545. View Abstract
  29. Intrinsic Control of Axon Regeneration. Neuron. 2016 05 04; 90(3):437-51. View Abstract
  30. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-232. View Abstract
  31. Reaching the brain: Advances in optic nerve regeneration. Exp Neurol. 2017 Jan; 287(Pt 3):365-373. View Abstract
  32. Restoration of skilled locomotion by sprouting corticospinal axons induced by co-deletion of PTEN and SOCS3. Nat Commun. 2015 Nov 24; 6:8074. View Abstract
  33. Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms. Neuron. 2015 Nov 18; 88(4):704-19. View Abstract
  34. Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS. Neuron. 2015 Jun 03; 86(5):1215-27. View Abstract
  35. Injury-induced decline of intrinsic regenerative ability revealed by quantitative proteomics. Neuron. 2015 May 20; 86(4):1000-1014. View Abstract
  36. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron. 2015 Mar 18; 85(6):1244-56. View Abstract
  37. SOCS3: a common target for neuronal protection and axon regeneration after spinal cord injury. Exp Neurol. 2015 Jan; 263:364-7. View Abstract
  38. Characterization of long descending premotor propriospinal neurons in the spinal cord. J Neurosci. 2014 Jul 09; 34(28):9404-17. View Abstract
  39. Signaling regulations of neuronal regenerative ability. Curr Opin Neurobiol. 2014 Aug; 27:135-42. View Abstract
  40. Independent control of aging and axon regeneration. Cell Metab. 2014 Mar 04; 19(3):354-6. View Abstract
  41. 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. View Abstract
  42. No simpler than mammals: axon and dendrite regeneration in Drosophila. Genes Dev. 2012 Jul 15; 26(14):1509-14. View Abstract
  43. Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron. 2012 Feb 09; 73(3):445-52. View Abstract
  44. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature. 2011 Nov 06; 480(7377):372-5. View Abstract
  45. Regenerative medicine: drawing breath after spinal injury. Nature. 2011 Jul 13; 475(7355):177-8. View Abstract
  46. Neuronal intrinsic mechanisms of axon regeneration. Annu Rev Neurosci. 2011; 34:131-52. View Abstract
  47. Axon regeneration: electrical silencing is a condition for regrowth. Curr Biol. 2010 Sep 14; 20(17):R713-4. View Abstract
  48. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci. 2010 Sep; 13(9):1075-81. View Abstract
  49. Neuronal intrinsic barriers for axon regeneration in the adult CNS. Curr Opin Neurobiol. 2010 Aug; 20(4):510-8. View Abstract
  50. PTEN/mTOR and axon regeneration. Exp Neurol. 2010 May; 223(1):45-50. View Abstract
  51. Intrinsic control of axon regeneration. J Biomed Res. 2010 Jan; 24(1):2-5. View Abstract
  52. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron. 2009 Dec 10; 64(5):617-23. View Abstract
  53. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science. 2009 Oct 23; 326(5952):592-6. View Abstract
  54. NAD and axon degeneration: from the Wlds gene to neurochemistry. Cell Adh Migr. 2009 Jan-Mar; 3(1):77-87. View Abstract
  55. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science. 2008 Nov 07; 322(5903):963-6. View Abstract
  56. Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J Neurosci. 2006 Sep 20; 26(38):9794-804. View Abstract
  57. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci. 2006 Aug; 7(8):617-27. View Abstract
  58. EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans. Science. 2005 Oct 07; 310(5745):106-10. View Abstract
  59. A local mechanism mediates NAD-dependent protection of axon degeneration. J Cell Biol. 2005 Aug 01; 170(3):349-55. View Abstract
  60. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron. 2005 Feb 03; 45(3):345-51. View Abstract
  61. 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. View Abstract
  62. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci. 2004 Mar; 7(3):261-8. View Abstract
  63. The Nogo signaling pathway for regeneration block. Annu Rev Neurosci. 2004; 27:341-68. View Abstract
  64. Signaling mechanisms of the myelin inhibitors of axon regeneration. Curr Opin Neurobiol. 2003 Oct; 13(5):545-51. View Abstract
  65. Involvement of the ubiquitin-proteasome system in the early stages of wallerian degeneration. Neuron. 2003 Jul 17; 39(2):217-25. View Abstract
  66. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature. 2002 Nov 07; 420(6911):74-8. View Abstract
  67. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature. 2002 Jun 27; 417(6892):941-4. View Abstract
  68. Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system. Sci STKE. 2002 Feb 12; 2002(119):re1. View Abstract

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Phone: 617-919-2353
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