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Wen-Jun Gao, Ph.D.

Assistant Professor

  • Department: Neurobiology and Anatomy
  • Specialty: Synaptic signaling and regulation of prefrontal neuronal circuitry
Research

Biography

Dr. Wen-Jun Gao received his Ph.D. from Shanghai Brain Research Institute, Chinese Academy of Sciences. He did his first postdoctoral training with Dr. Sarah L. Pallas at Georgia State University, then with Dr. Patricia S. Goldman-Rakic and Dr. David A. McCormick at Yale University School of Medicine. He is now an associate professor in the Department of Neurobiology and Anatomy at Drexel University College of Medicine.

Research Interests

  • Functional plasticity in the juvenile and adolescent prefrontal cortex and cognitive functions associated with this cortical region
  • Cellular and synaptic mechanisms of neuronal network activity in the prefrontal cortex
  • Molecular and cellular mechanisms underlying synaptic transmission and monoaminergic regulation of prefrontal cortex
  • Neurobiology of psychiatric disorders associated with prefrontal cortex and limbic systems, such as schizophrenia and ADHD

Research Summary

The cerebral cortex, especially the prefrontal cortex, is the most complex brain region in the central nervous system. Elucidating its diverse functions represents a major challenge in neurobiology. We are interested in the neuronal mechanisms underlying the synaptic signaling and monoaminergic regulation in the prefrontal cortical circuitry, as well as the critical issues involving neuropathology of mental disorders and other neurological diseases. Specifically, we are taking the advantages of in vivo and in vitro preparations to examine the neuronal signaling in both normal animals and clinical models of psychiatric disorders, such as schizophrenia and ADHD.

Work in the laboratory is currently focused in the following projects: 1) monoaminergic (dopamine and norepinephrine) regulation of synaptic transmissions and local circuitry in the prefrontal cortex; 2) how high-risk genes or epigenetic factors associated with schizophrenia affect the development of prefrontal cortex; 3) the roles of NMDA receptors in the schizophrenia pathological process; and 4) psychostimulant actions on the synaptic plasticity and trafficking of glutamatergic receptors. Our research involves a variety of morphological, physiological, pharmacological, and molecular approaches designed to elucidate the synaptic mechanisms underlying the prefrontal functions. Morphological studies include single-cell labeling, neuronal reconstruction, and immunocytochemistry. Physiological, pharmacological and molecular approaches include multiple whole-cell patch clamp recordings, drug applications, western blotting, and real-time PCR in fresh brain tissues, acute brain slices, and cell culture preparations. These approaches are mutually supportive with a comprehensive integration across disciplines.

Selected Grants Funded

"Phenotypic Diversity of Neurons Modulating Executive Function in ADHD"
Principal investigator: Wen-Jun Gao, Ph.D.
Co-investigator: Barry Waterhouse, Ph.D. (Neurobiology & Anatomy)
Commonwealth Universal Research Enhancement (CURE) Grant (2013)

Lab Personnel

Instructor:
Yanchun Li

Postdoctoral Fellows:
Melissa Snyder
Bo Xing

Graduate Students:
Kimberly Urban
Minjuan Wang
Yelena Guchina

Selected Publications

"Gestational methylazoxymethanol (MAM) exposure leads to NMDAR dysfunction in hippocampus during early development and lasting deficits in learning"
Melissa A. Snyder, Alicia E. Adelman, and Wen-Jun Gao 
Neuropsychopharmacology (in press, 2012)

"Evolution of the Study of Methylphenidate and its Actions on the Adult versus Juvenile Brain"
Kimberly R. Urban and Wen-Jun Gao
Journal of Attention Disorders (in press, 2012)

"Hyperdopaminergic Modulation of Inhibitory Transmission Is Dependent on GSK-3β Signaling-Mediated Trafficking of GABAa Receptors"
Yan-Chun Li, Min-Juan Wang, and Wen-Jun Gao
Joural of Neurochemistry (in pres, 2012)

"Distinct age-dependent effects of methylphenidate on developing and adult prefrontal neurons"
Kimberly Urban, Barry Waterhouse, and Wen-Jun Gao
Biological Psychiatry (in press, 2012)

"Prolonged exposure to NMDAR antagonist induces cell-type specific changes of glutamatergic receptors in rat prefrontal cortex"
Huai-Xing Wang and Wen-Jun Gao
Neuropharmacology 62:1808-1822 (2012)

"D2 receptor overexpression in the striatum leads to a deficit in inhibitory transmission and dopamine sensitivity in prefrontal cortex"
Yan-Chun Li, Christoph Kellendonk , Eleanor H. Simpson, Eric R. Kandel, Wen-Jun Gao
PNAS, 108(29): 12107-112. Commentary in Schizophrenia Research Forum (2011)

"Experimental strategies for investigating drug actions in ADHD and related attention disorders"
Agster K, Clark B, Gao WJ, Shumsky J, Wang HX, Berridge C and Waterhouse B
Anatomical Record, 294:1698-1712 (invited review, 2011)

"Group II metabotropic glutamate receptor agonist ameliorates MK-801-induced dysfunction of NMDA receptors via Akt/GSK-3b pathway"
Dong Xi*, Yan-Chun Li*, Melissa A. Snyder*, Ruby Y. Gao, Alicia E. Adelman, Wentong Zhang, Jed S. Shumsky, and Wen-Jun Gao (*these authors contribute equally)
Neuropsychopharmacology. 36:1260-1274  (2011)

"GSK-3 and hyperdopaminergic behaviors"
Yan-Chun Li and Wen-Jun Gao
Neuroscience & Biobehavioral Reviews. 35:645-654 (2011)

"Development of calcium-permeable AMPA receptors and their correlation with NMDA receptors in fast-spiking interneurons of rat prefrontal cortex"
Huai-Xing Wang and Wen-Jun Gao
The Journal of Physiology, 588(15):2823-2838 (2010)
selected for Faculty of 1000 Medicine (www.f1000medicine.com) and evaluated by Dr. Antonio Pisani.

"Dopamine D1 receptor-mediated NMDA receptor insertion depends on Fyn but not Src kinase pathway in prefrontal cortical neurons"
Jian-Li Hu*, Gang Liu*, Yan-Chun Li*, Wen-Jun Gao, Yue-Qiao Huang (*these authors contribute equally)
Molecular Brain, 3:20 (2010)

"Dopamine D1 receptor-mediated enhancement of NMDA receptor trafficking requires rapid PKC-dependent synaptic insertion in the prefrontal neurons"
Yan-Chun Li*, Gang Liu*, Jian-Li Hu*, Wen-Jun Gao* and Yue-Qiao Huang*  (*these authors contribute equally)
The Journal of Neurochemistry. 114:62-73  (2010)

"Activation of GSK-3b is required for hyperdopamine and D2 receptor mediated inhibition of synaptic NMDA receptor function in the rat prefrontal cortex"
Yan-Chun Li, Dong Xi, Joy Roman, Yue-Qiao Huang,  and Wen-Jun Gao
Journal of Neuroscience, 29(49):15551-15563 (2009)

"Role of dysbindin in dopamine receptor trafficking and cortical GABA function"
Ji Y, Yang F, Papaleo F, Wang HX, Gao WJ, Weinberger DR, Lu B
PNAS, 106:19593-19598 (2009)

"Dizocilpine (MK-801) induces distinct changes of N-methyl-d-aspartic acid receptor subunits in parvalbumin-containing interneurons in young adult rat prefrontal cortex"
Xi D , Zhang W, Wang HX, Stradtman GG III and Gao WJ
Int J Neuropsychopharmacol, 12:1395-1408 (2009)

"Cell-type specific development of NMDA receptors in the interneurons of rat prefrontal cortex"
Wang HX and Gao WJ
Neuropsychopharmacology, 34(8):2028-2040 (2009)

"NMDA receptor subunit expression in GABAergic interneurons in the prefrontal cortex: application of laser microdissection technique"
Xi D, Keeler B, Zhang W, Houle JD, and Gao WJ
Journal of Neuroscience Method, 176:172-181, 2009

"A specialized NMDA receptor function in the recurrent microcircuitry of the adult prefrontal cortex"
Wang HX, Stradtman GG III, Wang X-J, and Gao WJ
PNAS, 105(43):16791-16796, 2008

"Acute clozapine suppresses synchronized pyramidal synaptic network activity by increasing inhibition in the prefrontal cortex"
Gao WJ
The Journal of Neurophysiology 97:1196-1208, 2007

Recent Reviews and Book Chapters

"Evolution of the Study of Methylphenidate and its Actions on the Adult versus Juvenile Brain"
Kimberly R. Urban and Wen-Jun Gao
Journal of Attention Disorders (in press, 2012)

"The unique properties of the prefrontal cortex and mental illness"
Wen-Jun Gao*, Huai-Xing Wang, Melissa A. Snyder, and Yan-Chun Li
In When Things Go Wrong – Diseases and Disorders of the Human Brain, edited by Theo Mantamadiotis, Intech Publisher (2012)

"GSK-3 and hyperdopaminergic behaviors"
Yan-Chun Li and Wen-Jun Gao
Neuroscience & Biobehavioral Reviews. 35:645-654 (2011)

"Experimental strategies for investigating drug actions in ADHD and related attention disorders"
Agster K, Clark B, Gao WJ, Shumsky J, Wang HX, Berridge C and Waterhouse B
Anatomical Record, 294:1698-1712 (invited review, 2011)

"Dopaminergic and Glutamatergic Dysfunctions in the Neuropathophysiology of Schizophrenia"
Gao WJ
In Dopamine: Functions, Regulation and Health Effects, edited by Endo Kudo and Yuriko Fujii. Nova Publishers (2011)

Contact

  • Drexel University College of Medicine
  • 2900 Queen Lane, #243
    Philadelphia, PA 19129
  • Phone: work 215-991-8907
  • wgao@drexelmed.edu

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