J. Julius Zhu

Education

  • BS, Peking University
  • MS, Shanghai Brain Research Institute
  • PhD, University of Wisconsin Medical School
  • Postdoc, Max-Planck-Institut for Medical Research
  • Postdoc, Cold Spring Harbor Laboratory
  • Sabbatical, Norwegian University of Science & Technology

Primary Appointment

  • Professor, Pharmacology

Contact

Research Interest(s)

Neural Circuits in Healthy and Diseased Brains

Research Description

My students and I are interested in central neural circuits and synapses. We enjoy developing new experimental approaches that combine cutting-edge techniques, including rapid recombinant DNA delivery and replacement, multiple whole-cell recordings, genetically encoded sensors, single- and two-photon microscopy-based optogenetics and imaging, single-molecule force spectroscopy and immunoelectron microscopy. These technologies allow us to decipher the molecular and cellular regulations (e.g., nanoscale Ras/MAPK signaling) of synapses in neural circuits, as well as the organization and functions (e.g., salience selection) of neural circuits (Wang G, Wyskiel D, et al., Nature Protocols 10:397-412). Genetic defects of many signaling molecules are linked to a number of cognitive disorders, e.g., Akt/PKB and calcineurin with schizophrenia, BRaf with cardio-facio-cutaneous syndrome, Brag/IQSec with nonsyndromic X-linked mental retardation, CaMKII with Angelman syndrome, H-Ras with Costello syndrome, p38MAPK and JNK with Alzheimer's disease, PI3K with fragile X syndrome, PTEN with autism, Cowden and Bannayan-Riley-Ruvalcaba syndromes, RasGap NF1 with neurofibromatosis, Rsk with Coffin-Lowry syndrome and X-linked mental retardation, SHP-2 with Noonan syndrome, and tuberin with tuberous sclerosis. Altered interneuronal function is a common mechanism contributing to various neurological, mental and psychiatric disorders, including autisms, epilepsy, depression, Huntington’s disease, neurofibromatosis, schizophrenia, Tourette’s syndrome and trauma (Stornetta and Zhu, Neuroscientist 17: 54-78). Therefore, the findings from our research should guide the future development of treatments for these insidious diseases.

Selected Publications First-authored by Undergraduate Students:

Sheng Y, Zhang L, Su S, Tsai LH and Zhu JJ (2016) Cdk5 is a new rapid homeostatic transmission regulator capable of inducing the early Alzheimer-like synaptic pathology. Cerebral Cortex 26:2937-51.

Lee AJ, Wang G, Jiang X, Johnson SM, Hoang ET, Lante F, Stornetta RL, Beenhakker MP, Shen Y and Zhu JJ (2015) Canonical organization of layer 1 neuron-led cortical inhibitory and disinhibitory interneuronal circuits. Cerebral Cortex 25:2114-26.

Selected Publications First-authored by Graduate Students:

Kielland A, Bochorishvili G, Corson J, Zhang L, Rosin DL, Heggelund P and Zhu JJ (2009) Activity patterns govern synapse-specific AMPA-R trafficking between deliverable and synaptic pools. Neuron 62:84-101.

McCormack SG, Stornetta RL and Zhu JJ (2006) Synaptic AMPA receptor exchange maintains bidirectional plasticity. Neuron 50:75-88.

Selected Publications by PI:

Zhu JJ (2009) Activity level-dependent synapse-specific AMPA receptor trafficking regulates transmission kinetics. J Neurosci 29:6320-35.

Zhu JJ (2000) Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1 and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites. J Physiol (Lond) 526:571-87.

On April 25, 2017, the lab was featured in NBC29 nightly news (http://www.nbc29.com/story/35237995/uva-new-technique-will-help-in-search-for-new-cancer-treatments) and other media outlets.

On September 12, 2017, the lab was featured in CBS19 nightly news and other media outlets.

Postdoctoral research associate, graduate and undergraduate student position available, please contact: jjzhu@virginia.edu

Selected Publications

  • Lim C, Kang X, Mirabella V, Zhang H, Bu Q, Araki Y, Hoang E, Wang S, Shen Y, Choi S, Kaang B, Chang Q, Pang Z, Huganir R, Zhu J. BRaf signaling principles unveiled by large-scale human mutation analysis with a rapid lentivirus-based gene replacement method. Genes & development. 2017;31(6): 537-552. PMID: 28404629
  • Lim C, Wen C, Sheng Y, Wang G, Zhou Z, Wang S, Zhang H, Ye A, Zhu J. Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with Single-Molecule Force Spectroscopy. Small (Weinheim an der Bergstrasse, Germany). 2017. PMID: 28809097
  • Wang G, Bochorishvili G, Chen Y, Salvati K, Zhang P, Dubel S, Perez-Reyes E, Snutch T, Stornetta R, Deisseroth K, Erisir A, Todorovic S, Luo J, Kapur J, Beenhakker M, Zhu J. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy. Genes & development. 2015;29(14): 1535-51. PMID: 26220996
  • Lim C, Hoang E, Viar K, Stornetta R, Scott M, Zhu J. Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model. Genes & development. 2014;28(3): 273-89. PMID: 24493647
  • Jiang X, Wang G, Lee A, Stornetta R, Zhu J. The organization of two new cortical interneuronal circuits. Nature neuroscience. 2013;16(2): 210-8. PMID: 23313910 | PMCID: PMC3589105
  • Hu H, Qin Y, Bochorishvili G, Zhu Y, van Aelst L, Zhu J. Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008;28(31): 7847-62. PMID: 18667617 | PMCID: PMC2553221
  • Qin Y, Zhu Y, Baumgart J, Stornetta R, Seidenman K, Mack V, van Aelst L, Zhu J. State-dependent Ras signaling and AMPA receptor trafficking. Genes & development. 2005;19(17): 2000-15. PMID: 16107614 | PMCID: PMC1199571
  • Zhu Y, Pak D, Qin Y, McCormack S, Kim M, Baumgart J, Velamoor V, Auberson Y, Osten P, van Aelst L, Sheng M, Zhu J. Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron. 2005;46(6): 905-16. PMID: 15953419
  • Zhu Y, Zhu J. Rapid arrival and integration of ascending sensory information in layer 1 nonpyramidal neurons and tuft dendrites of layer 5 pyramidal neurons of the neocortex. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004;24(6): 1272-9. PMID: 14960597
  • Kolleker A, Zhu J, Schupp B, Qin Y, Mack V, Borchardt T, Köhr G, Malinow R, Seeburg P, Osten P. Glutamatergic plasticity by synaptic delivery of GluR-B(long)-containing AMPA receptors. Neuron. 2003;40(6): 1199-212. PMID: 14687553
  • Larkum M, Zhu J. Signaling of layer 1 and whisker-evoked Ca2+ and Na+ action potentials in distal and terminal dendrites of rat neocortical pyramidal neurons in vitro and in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2002;22(16): 6991-7005. PMID: 12177197
  • Zhu J, Malinow R. Acute versus chronic NMDA receptor blockade and synaptic AMPA receptor delivery. Nature neuroscience. 2002;5(6): 513-4. PMID: 11967548
  • Zhu J, Qin Y, Zhao M, Van Aelst L, Malinow R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell. 2002;110(4): 443-55. PMID: 12202034
  • Zhu J, Esteban J, Hayashi Y, Malinow R. Postnatal synaptic potentiation: delivery of GluR4-containing AMPA receptors by spontaneous activity. Nature neuroscience. 2000;3(11): 1098-106. PMID: 11036266
  • Larkum M, Zhu J, Sakmann B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature. 1999;398(6725): 338-41. PMID: 10192334
  • Zhu J, Connors B. Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex. Journal of neurophysiology. 1999;81(3): 1171-83. PMID: 10085344