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Chen-ENT-2013

Chu Chen, Ph.D.

Professor of Otorhinolaryngology and Neuroscience

2020 Gravier Street, Suite D
New Orleans, LA 70112

Phone: (504) 599-0918

Fax: (504) 599-0488

cchen@lsuhsc.edu

http://www.medschool.lsuhsc.edu/faculty/docs/CChen 21st NSR.pdf

 

 

Degrees

Education

1994-1996       Postdoctoral fellow, LSU Health Sciences Center, New Orleans

1989-1993       PhD, Tulane University, New Orleans

1983-1986       MS, Zhejiang Medical University, Hangzhou, China

1979-1983       BS, Nanjing University, Nanjing, China

Academic positions

7/2013 – present
Professor with tenure, Neuroscience Center and Department of Otorhinolaryngology, LSU Health Sciences Center in New Orleans

8/2012 - present
VA’s biomedical laboratory and clinical science research and development non-clinician intramural program member

7/2008 - 6/2013 
Associate Professor with tenure, Neuroscience Center and Department of Otorhinolaryngology, LSU Health Sciences Center in New Orleans

2002-2008
Tenure track Assistant Professor, Department of Otorhinolaryngology and Neuroscience Center of Excellence, LSUHSC

1998-2002
Research Assistant Professor, Department of Otorhinolaryngology and Neuroscience Center of Excellence, LSUHSC

1996-1998
Research Assistant Professor, Department of Otorhinolaryngology, LSUHSC

1988-1989
Lecturer, Department of Physiology, Zhejiang Medical University, Hangzhou, China

1986-1988
Instructor, Department of Physiology, Zhejiang Medical University, Hangzhou, China

Bio

Study Sections

  • Alzheimer’s Association grants (2004-2014)
  • National Science Foundation Grants
  • Irish Health Research Board grants, Ireland (2005-2006)
  • Indiana University Alzheimer’s Disease Research Grants (2008-2009)
  • Wellcome Trust Research grants, UK (2010)
  • NIH NIDA Special Emphasis Panel ZDA1 - JXR – D (06) (2011)
  • NIH CSR Special Emphasis Panel ZRG1 MDCN-R (40) P- 2014

  • Medical Research Council (MRC), UK (2012)
Research Interests

Keywords:
Neuromodulation of ion channels;
Neuroinflammation in hippocampal synaptic transmission and plasticity;
Mechanisms of neurodegenerative diseases
(e.g., Alzheimer’s disease, chronic traumatic encephalopathy);
COX-2 oxidative metabolism of endogenous cannabinoids in
synaptic activity and neuronal survival;
Mechanisms of marijuana-altered synaptic and cognitive function,
and cannabinoid tolerance.

Research Interests

Inflammation is now believed to be a common mechanism of disease.  Neuroinflammation, the inflammatory response that occurs in the nervous system, has been implicated in many brain disorders such as epilepsy, traumatic brain injury and stroke, and in neurodegenerative diseases such as multiple sclerosis, Parkinson’s and Alzheimer’s diseases. However, our understanding of the molecular mechanisms underlying neuroinflammation in the pathogeneses of neurodegenerative diseases is still elusive.  My research programs focus on neuroinflammation in synaptic plasticity and neurodegenerative diseases.  Specifically, I am interested in endocannabinoid and prostaglandin signaling in hippocampal synaptic plasticity and pathogenesis of Alzheimer’s disease.  Recent evidence shows that a large proportion of prostaglandins derives from hydrolysis of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) by the enzyme monoacylglycerol lipase (MAGL), that primarily metabolizes 2-AG in the brain.  While 2-AG exhibits anti-inflammatory and neuroprotective properties, prostaglandins (e.g., PGE2) are proinflammatory and neurotoxic.  Therefore, MAGL plays an important role in regulation of endocannabinoid 2-AG and prostaglandin signaling (See inset).  Thus, inhibition of MAGL will result in strengthening anti-inflammatory and neuroprotective 2-AG signaling, while reducing proinflammatory arachidonic acid and eicosanoid levels.  We are currently addressing this important issue as to whether inactivation of MAGL is able to alter hippocampal synaptic signaling and reduce neuropathology of Alzheimer’s disease and whether epigenetic mechanisms such as noncoding microRNAs are involved in regulation of synaptic plasticity and neuropathology by endocannabinoid and prostaglandin signaling.

cchen image new 071312

 

Teaching Activities

2002-present Lecture: Investigative Neuroscience 203 to PhD graduate program students

2002-present Lecture: Molecular Neurobiology 250 to PhD graduate program students

 

Selected Publications
  1. Zhang J., Hu M., Teng Z., Tang Y. & Chen C. (2014) Synaptic and cognitive improvements by inhibition of 2-AG metabolism are through upregulation of microRNA-188-3p in a mouse model of Alzheimer’s disease.  Journal of Neuroscience (In press).
     
  2. Xu J. & Chen C. (2014) Endocannabinoids in synaptic plasticity and neuroprotection. Neuroscientist (In press) DOI: 10.1177/1073858414524632
     
  3. Chen R., Zhang J., Fan N., Teng Z., Wu Y., Yang H., Tang Y., Sun H., Song Y. & Chen C. (2013) Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.  Cell 155:1154-1165.
    (Featured and highlighted in Cell:http://www.elsevier.com/connect/preventing-marijuana-induced-memory-problems-with-OTC-painkillers;Science: http://news.sciencemag.org/brain-behavior/2013/11/painkillers-may-curb-memory-loss-medical-marijuana; Science Signaling: Snuffing Out Marijuana Inflammation. 6(304):ec291,2013: http://stke.sciencemag.org/cgi/content/abstract/6/304/ec291; Nature: Painkiller kills the bad effects of pot. 503(7477):440,2013: http://www.nature.com/nature/journal/v503/n7477/full/503440b.html; Nature Reviews Neuroscience: Memory: a boost for medical marijuana? 15(1): 2-3,2014: http://www.nature.com/nrn/journal/v15/n1/full/nrn3659.html; and covered by various news media)
  4. Chen R., Zhang J., Wu Y., Wang D., Feng G., Tang Y.P., Teng Z. & Chen C. (2012) Monoacylglycerol lipase is a therapeutic target for Alzheimer’s diseaseCell Reports 2:1329-1339 (Covered by various news media).
  5. He H., Mahnke A., Doyle S., Fan N., Wang C., Hall B., Tang Y.P., Inglis F., Chen C. & Erickson J.D. (2012) A neurodevelopmental role for VGLUT2 in pyramidal neuron maturation and spatial learningJournal of Neuroscience 32:15886-15901

  6. Pan W., Hsuchou H., Jayaram B., Khan R.S., Huang E.Y., Wu X., Chen C. & Kastin A.J. (2012) Leptin action on nonneuronal cells in the CNS: potential clinical applications.  Annals of the New York Academy of Sciences 1264:64-71.

  7. Xu J., Zhang J. & Chen C., (2012) Long-lasting potentiation of hippocampal synaptic transmission by direct cortical input is mediated via endocannabinoidsJournal of Physiology (Lond) 590:2305-2315.
     
  8. Du H., Chen X., Zhang J. & Chen C. (2011) Inhibition of COX-2 expression by endocannabinoid 2-arachidonoylglycerol is mediated by PPAR-gamma.  British Journal of Pharmacology (2011) 163:1533-1549.
     
  9. Chen X., Zhang J. & Chen C. (2011) Endocannabinoid 2-arachidonoylglycerol protects neurons against beta-amyloid insultsNeuroscience 178:159-168.
     
  10. Yu T., Li Z., Jia Z., Clapcote S.J., Liu C., Li S., Asrar S.,  Pao A., Chen R., Fan N., Carattini-Rivera S., Bechard A.R., Spring S., Henkelman R.M., Stoica G., Matsui S-I., Nowak N.J., Roder J.C., Chen C., Bradley A. & Yu Y.E.  (2010) A mouse model of Down Syndrome trisomic for all human chromosome 21 syntenic regionsHuman Molecular Genetics 19:2780–2791.
     
  11. Chen C. (2010) COX-2’s new role in inflammationNature Chemical Biology 6: 401-402.
     
  12. Xu J., Zhang J. & Chen C. (2010) Endocannabinoids differentially modulate long-term depression in rat hippocampal CA1 pyramidal neuronsPLoS ONE  5:e10306.
     
  13. Sang N., Zhang J. & Chen C.  (2010) Anandamide potentiation of miniature spontaneous excitatory synaptic transmission is mediated via IP3 pathwayNeurochemistry International  56:590-596.
     
  14. Fan N., Yang H., Zhang J. & Chen C. (2010) Reduced expression of glutamate receptors and phosphorylation of CREB are responsible for Δ9-THC-impaired hippocampal synaptic plasticity.  Journal of Neurochemistry 112:691-702.
     
  15. Grewal S., Defamie N., Zhang X., Gois S.D., Shawki A., Mackenzie B., Chen C., Varoqui H. & Erickson J.D. (2009) SNAT2 amino-acid transporter is regulated by osmolytes of the SLC6 GABA transporter subfamily and may play no role in delivering glutamine for spontaneous glutamatergic transmission.  Journal of Biological Chemistry  284:11224-11236.
     
  16.  Yang H., Zhang J., Breyer R.M. & Chen C. (2009) Altered hippocampal long-term synaptic plasticity in mice deficient in the PGE2 EP2 receptor. Journal of Neurochemistry  108: 295-304.
     
  17. Zhang J. & Chen C. (2008) Endocannabinoid 2-arachidonoylglycerol protects neurons by limiting COX-2 elevationJournal of Biological Chemistry 283: 22601–22611.
     
  18. Yang H. & Chen C.  (2008) COX-2 in synaptic signaling. Current Pharmaceutical Design  14: 1443-1451.
     
  19. Yang H., Zhang J., Andreasson K. & Chen C. (2008)COX-2 Oxidative metabolism of endocannabinoids augments hippocampal synaptic plasticityMolecular and Cellular Neuroscience  37: 682-695.
     
  20. Sang N., Zhang J. & Chen C. (2007) COX-2 oxidative metabolite of endocannabinoid 2-AG enhances excitatory glutamatergic synaptic transmission and induces neurotoxicity. Journal of Neurochemistry 102: 1966-1977.
     
  21. Sang N. & Chen C. (2006)  Lipid signaling and synaptic plasticityNeuroscientist  12: 425-434.
     
  22. Sang N., Zhang J. & Chen C. (2006) PGE2 glycerol ester, a COX-2 oxidative metabolite of 2-arachidonoyl glycerol, modulates inhibitory synaptic transmission in mouse hippocampal neuronsJournal of Physiology (Lond) 572: 735-745.
     
  23. Sang N., Zhang J., Marcheselli V., Bazan, N.G. & Chen C. (2005) Postsynaptically synthesized prostaglandin E2 modulates hippocampal synaptic transmission via a presynaptic PGE2 EP2 receptorJournal of Neuroscience  25: 9858-9870.
     
  24. Gois S.D., Schafer MK-H., Defamie N., Chen C, Ricci A, Weihe E, Varoqui H & Erickson JD.  (2005) Homeostatic scaling of vesicular glutamate and GABA transporters expression in rat neocortical circuitsJournal of Neuroscience  25:7121-7133.
     
  25. Zhu P., Genc A., Zhang X., Zhang J., Bazan N.G. & Chen C. (2005) Heterogeneous expression and regulation of PGE2 receptors in the hippocampus.   Journal of Neuroscience Research  81: 817-826.
     
  26. Chen C. & Bazan N.G.  (2005) Endogenous PGE2 regulates membrane excitability and synaptic transmission  in rat hippocampal CA1 pyramidal neuronsJournal of Neurophysiology  93: 929-941.
     
  27. Chen C.  (2004) ZD7288 inhibits postsynaptic glutamate receptor-mediated responses at hippocampal perforant path-granule cells synapses.   European Journal of Neuroscience 19: 643-649.
     
  28. McDermott C.M., LaHoste G.L., Chen C., Musto A., Bazan N.G. & Magee J.C. (2003) Sleep deprivation causes behavioral, synaptic and membrane excitability alterations in hippocampal neuronsJournal of Neuroscience  23: 9687-9695.
     
  29. Chen C., Magee J.C. & Bazan N.G., (2002)  Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticityJournal of Neurophysiology  87:2851-2857.
     
  30. Rodriguez de Turco E.B.R., Tang W., Topham M.K., Sakane F., Marcheselli V.L., Chen C., Taketomi A., Prescott S. & Bazan N.G.  (2001) Diacylglcerol kinase epsilon regulates suizure susceptibility and long-term potentiation through arachidonoyl-inositol lipid signalingProceedings of National Academy of Science USA 98: 4740-4745.
     
  31. Chen C., Magee J.C., Marcheselli V., Hardy M. & Bazan N.G. (2001) Attenuated long-term potentiation in hippocampal dentate gyrus neurons of mice deficient in the PAF receptorJournal of Neurophysiology  85: 384-390.
Additional Info

Current Funding   

Source: NIH-NINDS   R01NS076815 6/15/2012-3/31/2017

Title: Endocannabinoids in neurodegenerative diseases.

Role on Grant: PI. 

 

Source:  NIH-NIA  R21AG039669  4/1/2011-3/31/2013

Title: MAGL inhibition in prevention and treatment of Alzheimer’s disease.

Role on Grant: PI.

 

Source:   NIH-NINDS   R01NS054886   6/1/2007-11/30/2012

Title: Endocannabinoids in COX-2 mediated synaptic modification and neurotoxicity.

Role on Grant: PI.