Zhigang He

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

Professor of Neurology

Boston Children's Hospital

F.M. Kirby Neurobiology Center

Center for Life Science

Boston, MA 02115, USA

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.

Research Overview

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.

Selected Recent Publications

1. Zhang Z, Su J, Tang J, Chung L, Page JC, Winter CC, Liu Y, Kegeles E, Conti S, Zhang Y, Biundo J, Chalif JI, Hua CY, Yang Z, Yao X, Yang Y, Chen S, Schwab JM, Wang KH, Chen C et al. (2024) Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone. Cell 187:3427-3444.e21.

2. Liu X, Xin DE, Zhong X, Zhao C, Li Z, Zhang L, Dourson AJ, Lee L, Mishra S, Bayat AE, Nicholson E, Seibel WL, Yan B, Mason J, Turner BJ, Gonsalvez DG, Ong W, Chew SY, Ghosh B, Yoon SO et al. (2024) Small-molecule-induced epigenetic rejuvenation promotes SREBP condensation and overcomes barriers to CNS myelin regeneration. Cell 187:2465-2484.e22.

3. Winter CC, Jacobi A, Su J, Chung L, van Velthoven CTJ, Yao Z, Lee C, Zhang Z, Yu S, Gao K, Duque Salazar G, Kegeles E, Zhang Y, Tomihiro MC, Zhang Y, Yang Z, Zhu J, Tang J, Song X et al. (2023) A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons. Nature 624:403-414.

4. Squair JW, Milano M, de Coucy A, Gautier M, Skinnider MA, James ND, Cho N, Lasne A, Kathe C, Hutson TH, Ceto S, Baud L, Galan K, Aureli V, Laskaratos A, Barraud Q, Deming TJ, Kohman RE, Schneider BL, He Z et al. (2023) Recovery of walking after paralysis by regenerating characterized neurons to their natural target region. Science 381:1338-1345.

5. Takatoh J, Prevosto V, Thompson PM, Lu J, Chung L, Harrahill A, Li S, Zhao S, He Z, Golomb D, Kleinfeld D, Wang F (2022) The whisking oscillator circuit. Nature 609:560-568.