Hwai-Jong (HJ) Cheng

image of Hwai-Jong (HJ) Cheng

Professor

Departments

Center for Neuroscience
Pathology - Medicine
Neurobiology, Physiology and Behavior

Offices and Labs

1515 Newton Court / Room 604E
(530) 752-5323
1515 Newton Court / Room 603
(530) 754-4159

Profile Introduction

Axon Guidance and Axon Refinement

Degrees

1995 PhD (Cell and Developmental Biology) Harvard University
1989 MD (Medicine) National Taiwan University

Research Contribution

1) Using ferret as a model, we started to address the role of neural activity in refining the anatomical and functional connections of the visual system. We have identified activity-dependent axon-axon competition as an important mechanism for axon terminal targeting during development and revealed the role of stage III retinal waves in promoting circuit refinement. 2) Axon pruning in the brain had been recognized as a fundamental process for developmental plasticity, but the understanding of the molecular and cellular regulations for this process had been challenging. Focusing on the pruning events in hippocampal and visual circuits, we developed immuno-electron microscopic and imaging analysis to investigate the cellular mechanisms. These studies demonstrate that the axon branches to be pruned often form synapses, suggesting the importance of neural activity for the process. 3) Using mouse and C. elegans genetics, we investigated the role of the DISC1 (Deleted in Schizophrenia 1) gene in neural development. These studies have revealed the previously unknown function of DISC1 in regulation of adult-generated neurons in the hippocampus and established a heterologous line in C. elegans for future investigations. 4) Using mouse genetics, we generated plexin mutant mice to address the in vivo functions of semaphorin-plexin signaling in axon guidance. These studies demonstrate the differential roles of plexin family members in guiding axons in vivo, and unexpectedly reveal the role of semaphorin-plexin signaling in regulating stereotyped axon pruning in the central nervous system. 5) My early research work laid the foundation for the use of AP (alkaline phosphatase) fusion protein techniques and the molecular mechanisms of topographic map in the visual system. Prior to my early research, Ephs were orphan receptors without known functions. I developed the AP fusion expression cloning techniques and identified ephrins. I then developed the RAP (receptor AP) and LAP (Ligand AP) to demonstrate Ephs and ephrins are the “Sperry” molecules for establishing the visual topographic map. Both the AP fusion technique and the biology of Ephs and ephrins in the formation of topographic neural circuits have contributed significantly to the progress of the field.

Research Interests

Axon Guidance and Axon Refinement

We are interested in how mature neural circuits are formed. We have used model organisms such as mouse, C. elegans, and ferret to study how the axonal connections are refined throughout development. These approaches allow us to address basic issues regarding axon refinement at molecular, cellular and systems level.

 

Awards

Pharmacia Biotech & Science Prize for Young Scientists in Molecular Biology -1996
Howard Hughes Medical Institute Physician Postdoctoral Fellow - 1997
Whitehall Foundation Award - 2003
Alfred P. Sloan Foundation Award - 2004
Klingenstein Fellowship Award - 2004
Faculty Service Award, Neuroscience Graduate Group, UC Davis - 2012
UC Davis Academic Advising Award – Outstanding Faculty Advisor - 2015

Department and Center Affiliations

Center for Neuroscience
Department of Neurobiology, Physiology, & Behavior (College of Biological Sciences)
Department of Pathology and Laboratory Medicine (School of Medicine)

ProfessionalSocieties

Society for Neuroscience

CBS Grad Group Affiliations

Neuroscience
Biochemistry, Molecular, Cellular and Developmental Biology

Specialties / Focus

Biochemistry, Molecular, Cellular and Developmental Biology
  • Molecular Genetics
  • Cell Biology
  • Developmental Biology
  • Neurobiology
  • Signal Transduction
  • Vision
  • Stem Cell Biology

Labs

Cheng Lab website
  • Julie Luu (Postdoctoral fellow)
  • Arash Ng (Postdoctoral fellow)
  • Lindsay Cameron (Junior specialist)
  • Melanie Yoshihara (Junior specialist)
  • Atrin Toussi (undergraduate assistant)
  • Ana Marija Sola (undergraduate assistant)

Teaching Interests

Developmental neurobiology
Neurobiology
Human brain and disease

Courses

NPB 12 Human Brain and Disease (Fall)
NPB 100 Neurobiology (Fall)
NSC 224AB Molecular and Development Neuroscience (Spring)

Publications

4/18/2011 9:02:16 AM
  • Davis, Z.W., Chapman, B., and Cheng, H.-J..  Increasing spontaneous retinal activity before eye opening accelerates the development of geniculate receptive fields. J. Neurosci. 35:14612-14623 (2015).

  • Failor, S., Chapman, B., and Cheng, H.-J..  Retinal waves regulate afferent terminal targeting in the early visual pathway. Proc. Natl. Acad. Sci. USA 112: E2957-E2966 (2015).

  • Liu, W.-W., Chen, S.-Y., Cheng, C.-H., Cheng, H.-J.* and Huang, P.-H.*.  Blm-s, a BH3-only protein enriched in postmitotic immature neurons, is transcriptionally upregulated by p53 during DNA damage.  Cell Reports 9: 166-79 (2014). (*Co-corresponding authors)

  • Chen, S.-Y., Huang, P.-H. and Cheng, H.-J.. Disrupted-in-Schizophrenia 1-mediated axon guidance involves TRIO-RAC-PAK small GTPase pathway signaling. Proc. Natl. Acad. Sci. USA 108: 5861-5866 (2011).
  • Cheng, T.-W., Liu, X.-B., Faulkner, R. L., Stephan, A. H., Barres, B. A., Huberman, A. D., and Cheng H.-J.. Emergence of lamina-specific retinal ganglion cell connectivity by axon arbor retraction and synapse elimination. J. Neurosci. 30:16376-16382 (2010).
  • Vanderhaeghen, P. and Cheng, H.-J.. Guidance molecules in axon pruning and cell death. Cold Spring Harb. Perspect. Biol. 2:a001859 (2010)
  • Faulkner, R. L., Jang, M.-H., Liu, X.-B., Duan, X., Sailor, K. A., Kim, J. Y., Ge, S., Jones, E. G., Ming, G.-L., Song, H., and Cheng, H.-J.. Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain. Proc. Natl. Acad. Sci. USA 105:14157- 14162 (2008)
  • Low, L. K., Liu, X.-B., Faulkner, R. L., Coble, J., and Cheng, H.-J.. Plexin signaling selectively regulates the stereotyped pruning of corticospinal axons from visual cortex. Proc. Natl. Acad. Sci. USA 105:8136-8141 (2008)
  • Waimey, K.E., Huang, P.-H., Chen, M. and Cheng, H.-J. Plexin-A3 and plexin-A4 restrict the migration of sympathetic neurons but not their neural crest precursors. Developmental Biology 315:448-458 (2008)
  • Lucanic, M., Kiley, M., Ashcroft, N., LEtoile, N. and Cheng H.-J.. The C. elegans p21 activated kinases are differentially required for UNC-6/Netrin mediated commissural motor axon guidance. Development 133:4549-4559 (2006)
  • Liu, X.-B., Low, L. K., Jones, E. G., and Cheng, H.-J.. Stereotyped Axon Pruning via Plexin Signaling is Associated with Synaptic Complex Elimination in the Hippocampus. J. Neurosci. 25:9124-9134 (2005)
  • Yaron, A, , Huang, P.-H., Cheng, H.-J.*, and Tessier-Lavigne, M.*. Differential requirement for Plexin-A3 and -A4 in mediating responses of sensory and sympathetic neurons to distinct class 3 Semaphorins. Neuron 45:513-523 (2005) (*co-senior authors)
  • Bagri, A. *, Cheng, H.-J. *, Yaron, A., Pleasure, S. J., and Tessier-Lavigne, M.. Stereotyped pruning of long hippocampal axon branches triggered by retraction inducers of the Semaphorin family. Cell 113: 285-299. (2003) (*equal contributions)
  • Cheng, H.-J.*, Bagri, A.*, Yaron, A., Stein, E., Pleasure, S. J., and Tessier-Lavigne, M.. Plexin-A3 Mediates Semaphorin Signaling and Regulates the Development of Hippocampal Axonal Projections. Neuron 32:249-63. (2001) (*equal contributions)
  • Nakamoto, M.*, Cheng, H.-J.*, Friedman, G. C., McLaughlin, T., Hansen, M. J., Yoon, C. H., O'Leary, D. D. M. and Flanagan, J. G.. Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo. Cell 86:755-766 . (1996) (*equal contributions)
  • Cheng, H.-J., Nakamoto, M., Bergemann, A. D. and Flanagan, J. G.. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell 82:371-381. (1995)
  • Cheng, H.-J. and Flanagan. J.G.. Identification and cloning of ELF-1, a developmentally-expressed ligand for the Mek4 and Sek receptor tyrosine kinases. Cell 79:157-168. (1994)