Principal Investigator

Yun Wang
Chronic Pain and Its Psychiataic Comorbidity, Neural Development and Brain Disorders, Nerual Injury and Repair




Research Interests:

We are interested in neural signal transduction. We use multidisciplinary approaches, integrating molecular biology, genetics, neurobiology, biochemistry, imaging, electrophysiology and behavior(1) to identify key molecules and brain basis playing important roles in the development and maintenance of chronic pain and pain-related negative emotions. Chronic pain could be regarded as a kind of maladaptive memory usually accompanying with pain-related negative emotions. Our studies will provide important theoretical basis for elucidation of both the peripheral and central cerebral mechanisms of chronic pain and shed new insight in the development of clinical analgesics for chronic pain. (2) to explore signal transduction pathways in neural development, neural injury and repair, and the mechanisms of neurodegenerative disease. Neural development is a precisely regulated process and the abnormality of this process will result in a variety of neuropsychiatric disorders. Our studies focus on understanding the key mechanisms and molecules of regulation in neural development and neural repair, which provide possible therapies for related neuropsychiatric disorders.



Selected Publications:

1. Wang GQ*, Cen C*, Cao S*, Li C*, Wang N, Zhou Z, Liu XM, Xu Y, Tian NX, Zhang Y, Wang J, Wang LPCA and Wang YCA. Deactivation of excitatory neurons in the contralateral prelimbic cortex via Cdk5 promotes pain sensation and anxiety. Nature Communications, 2015 in press.

2. Zhang Y*, Wang N*, Su P, Lu J, Wang YCA. Disruption of dopamine D1 receptor phosphorylation at serine 421 attenuates cocaine-induced behaviors in mice. Neurosci Bull. 2014 Dec;30(6):1025-35.

3. Li Y*, Hu F*, Chen HJ*, Du YJ, Xie ZY, Zhang Y, Wang JCA, Wang YCA. LIMK-dependent actin polymerization in primary sensory neurons promotes the development of inflammatory heat hyperalgesia in rats. Sci Signal. 2014 Jun 24;7(331): ra61.

4. Wang N*, Su P*, Zhang Y*, Lu J*, Xing BM, Kang K, Li WQ, Wang YCA. Protein kinase D1-dependent phosphorylation of dopamine D1 receptor regulates cocaine-induced behavioral responses. Neuropsychopharmacol.  2014 Apr;39(5):1290-301.

5. Qi C*, Liu SM*, Qin R*, Zhang Y, Wang GQ, Shang, YF, Wang YCA and Liang JCA. Coordinated Regulation of Dendrite Arborization by Epigenetic Factors CDYL and EZH2. J Neurosci. 2014 Mar 26;34(13):4494-508. .

6. Li G, Wang YCA. Protein kinase D: a new player among the signaling proteins that regulate functions in the nervous system. Neurosci Bull. 2014 Jun;30(3):497-504.

7. Wang N*, Su P*, Zhang Y*, Lu J*, Xing BM, Kang K, Li WQ, Wang YCA. Protein kinase D1-dependent phosphorylation of dopamine D1 receptor regulates cocaine-induced behavioral responses. Neuropsychopharmacol. 2014 Apr;39(5):1290-301.

8. Xing BM*, Yang YR*, Du JX*, Chen HJ, Qi C, Huang ZH, Zhang YCA and Wang YCA. Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B.  J Neurosci. 2012 Oct 17;32(42):14709-21.

9. Zhu YB*, Kang K*, Zhang Y, Qi C, Li G, Yin DMCA and Wang YCA. PLD1 negatively regulates dendritic branching. J Neurosci. 2012 Jun 6;32 (23):7960-9.

10. Wang KWCA, Wang YCA. Negative modulation of NMDA receptor channel function by DREAM/calsenilin/KChIP3 provides neuroprotection?  Front Mol Neurosci. (Invited review) 2012 Mar 15;5:39.

11. Chen HJ*, Xie WY*, Hu F, Zhang Y, Wang J, Wang YCA. Disruption of δ-opioid receptor phosphorylation at Threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.  Neurosci Bull. 2012 Apr;28(2):182-92. 

12. Zhang Y*, Su P*, Liang P, Liu T, Liu X, Liu XY, Zhang B, Han T, Zhu YB, Yin DM, Li JF, Zhou Z, Wang KW, Wang YCA. The DREAM protein negatively regulates the NMDA receptor through interaction with the NR1 subunit.  J Neurosci. 2010 Jun 2;30(22):7575-86.

13. Xie WY*, He Y*, Yang YR, Li YF, Kang K, Xing BM, Wang YCA. Disruption of cdk5- associated phosphorylation of residue threonine-161 of the delta opioid receptor: impaired receptor function and attenuated morphine antinociceptive tolerance. J Neurosci. 2009 Mar 18;29(11):3551-64.

14. Yin DM, Huang YH, Zhu YB, Wang YCA. Both the establishment and maintenance of neuronal polarity require the activity of protein kinase D in the Golgi apparatus. J Neurosci. 2008 Aug 27;28(35):8832-43..

15. Zhu HH*, Yang YR*, Zhang H, Han Y, Li YF, Zhang Y, Yin DM, He QH, Zhao ZQ, Blumberg PM, Han JS, Wang YCA. Interaction between protein kinase D1 and transient receptor potential V1 in primary sensory neurons is involved in heat hypersensitivity. Pain. 2008 Jul 31;137(3):574-88.

16. He Y, Li HL, Xie WY, Yang CZ, Yu AC, Wang YCA. The presence of active Cdk5 associated with p35 in astrocytes and its important role in process elongation of scratched astrocyte. Glia. 2007 Apr 15;55(6):573-83.

17. Yang YR, He Y, Zhang Y, Li Y, Li YF, Han Y, Zhu HH, Wang YCA. Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia. Pain. 2007 Jan; 127(1-2):109-20.

18. Wang YCA, Kedei N, Wang M, Wang QJ, Huppler AR, Toth A, Tran R, Blumberg PM. The interaction between PKCmu and vanilloid receptor type 1. J Biol Chem. 2004 Dec 17;279(51):53674-82.

19. Wang Y, Xie WY, He Y, Wang M, Yang YR, Zhang Y, Yin DM, Jordan-Sciutto KL, Han JS, Wang Y CA. Role of CDK5 in neuroprotection from serum deprivation by mu-opioid receptor agonist. Exp Neurol. 2006 Dec;202(2):313-23.

20. Wang YCA, Zhang Y, Wang W, Cao Y, Han JS. Effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception. Exp Neurol. 2005 Mar; 192 (1):156-62.

21. Sun RH, Wang HC, Wan Y, Jing Z, Luo F, Han JS, and Wang YCA. Suppression of neuropathic pain by peripheral electrical stimulation in rats: mu-opioid receptor and NMDA receptor implicated. Exp Neurol. 2004 May;187(1):23-9.

22. Wang YCA. The functional regulation of TRPV1 and its role in pain sensitization. Neurochem Res. 2008 Oct;33(10):2008-12. (review)

23. Li Y, Zhang Y, Han JS, Wang YCA. Distinct responses of DREAM to electroacupuncture stimulation with different frequency under physiological and inflammatory conditions in rats. Neurochem Res. 2008 Oct;33(10):2070-7.

24. Zhang Y, Li Y, Yang YR, Zhu HH, Han JS, Wang YCA. Distribution of downstream regulatory element antagonist modulator (DREAM) in rat spinal cord and upregulation of its expression during inflammatory pain. Neurochem Res. 2007 Sep;32(9):1592-9.

25. Wang Y, Toth A, Tran R, Szabo T, Welter JD, Blumberg PM, Lee J, Kang SU, Lim JO, Lee J.  High affinity partial agonists of vanilloid receptor. Mol Pharmacol. 2003 Aug;64(2):325-33.

26. Wang Y, Szabo T, Welter JD, Toth A, Tran R, Lee J, Kang SU, Suh YG, Blumberg PM, Lee J.  High affinity antagonists of the vanilloid receptor. Mol Pharmacol. 2002 Oct;62(4):947-56.

27. Wang Y, Wang XM, Han JS. Discrimination between peptide and non-peptide opioid agonists on the transcription of opioid receptors in two cell lines. Life Sci. 2001 May 4;68(24):2731-40.

28. Chen ZW, Yang K, Wang YCA, Han JS. The metabolic evidence of synergistic interaction between DAMGO and DPDPE on undifferentiated SH-SY5Y cells. NeuroReport. 2001 Mar 26;12(4):845-9.

29. Chen ZW, Yang K, Wang YCA, Han JS. The metabolic evidence of synergistic effect between ohmefentanyl and [D-Pen2, D-Pen5] enkephalin on differentiated SH-SY5Y cells in humans. Neurosci Lett. 2001 Feb 9;298(3):199-202.

30. Sun R, Wang YCA, Zhao CS, Chang JK, Han JS. Changes in Brain content of   nocicepin/orphanin FQ and endomorphin 2 in a rat model of neuropathic pain. Neurosci Lett. 2001 Sep 21;311(1):13-6.

31. Huang C, Wang YCA, Chang JK, Han JS. Endomorphin and mu-opioid receptors in mouse brain mediate the analgesic effect induced by 2 Hz but not 100 Hz electroacupuncture stimulation. Neurosci Lett. 2000 Nov 24;294(3):159-62.

32. Wang Y, Huang C, Cao Y, Han JS. Repeated administration of low dose ketamine for the treatment of monoarthritic pain in rat. Life Sci. 2000 Jun 8;67(3):261-7.

33. Lazar J, Braun DC, Toth A, Wang Y, Pearce LV, Pavlyukovets VA, Blumberg PM, Garfield SH, Wincovitch S, Choi HK, Lee J. Kinetics of penetration influence the apparent potency of vanilloids on TRPV1. Mol Pharmacol. 2006 Apr;69(4):1166-73.

34. Zhang Y, Xiang B, Li YM, Wang Y, Wang X, Wang YN, Wu LL, Yu GY. Expression and characteristics of vanilloid receptor 1 in the rabbit submandibular gland. Biochem Biophys Res Commun. 2006 Jun 23;345(1):467-73.

35. Toth A, Wang Y, Kedei N, Tran R, Pearce LV, Kang SU, Jin MK, Choi HK, Lee J, Blumberg PM. Different vanilloid agonists cause different patterns of calcium response in CHO cells heterologously expressing rat TRPV1. Life Sci. 2005 May 6; 76(25):2921-32.

36. Lee J, Jin MK, Kang SU, Kim SY, Lee J, Shin M, Hwang J, Cho S, Choi YS, Choi HK, Kim SE, Suh YG, Lee YS, Kim YH, Ha HJ, Toth A, Pearce LV, Tran R, Szabo T, Welter JD, Lundberg DJ, Wang Y, Lazar J, Pavlyukovets VA, Morgan MA, Blumberg PM. Analysis of structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]-thiourea analogues as TRPV1 antagonists. Bioorg Med Chem Lett. 2005 Sep 15;15(18):4143-50.

37. Lee J, Kang SU, Kil MJ, Shin M, Lim JO, Choi HK, Jin MK, Kim SY, Kim SE, Lee YS, Min KH, Kim YH, Ha HJ, Tran R, Welter JD, Wang Y, Szabo T, Pearce LV, Lundberg DJ, Toth A, Pavlyukovets VA, Morgan MA, Blumberg PM. Analysis of structure-activity relationships for the 'A-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as TRPV1 antagonists. Bioorg Med Chem Lett. 2005 Sep 15;15(18):4136-42.

38. Lee J, Kang SU, Lim JO, Choi HK, Jin MK, Toth A, Pearce LV, Tran R, Wang Y, Szabo T, Blumberg PM. N-[4-(Methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: analysis of structure–activity relationships for the ‘C-Region’. Bioorg Med Chem. 2004 Jan 15;12(2):371-85.

39. Lee J, Kim SY, Lee J, Kang M, Kil MJ, Choi HK, Jin MK, Wang Y, Toth A, Pearce LV, Lundberg DJ, Tran R, Blumberg PM. Analysis of structure-activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism. Bioorg Med Chem. 2004 Jul 1;12(13):3411-20.

40. Lee J, Kang SU, Choi HK, Lee J, Lim JO, Kil MJ, Jin MK, Kim KP, Sung JH, Chung SJ, Ha HJ, Kim YH, Pearce LV, Tran R, Lundberg DJ, Wang Y, Toth A, Blumberg PM. Analysis of structure-activity relationships for the 'B-region' of N-(3-acyloxy-2-benzylpropyl)-N(')-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: discovery of an N-hydroxythiourea analogue with potent analgesic activity. Bioorg Med Chem Lett. 2004 May 3;14(9):2291-7.

41. Tang XQ, Wang Y, Huang ZH, Han JS, Wan Y. Adenovirus-mediated GDNF ameliorates corticospinal neuronal atrophy and motor function deficits in rats with spinal cord injury. NeuroReport. 2004 Mar 1;15(3):425-9.

42. Fang M, Wang Y, He QH, Sun YX, Deng LB, Wang XM, Han JS. Glial cell line-derived neurotrophic factor contributes to delayed inflammatory hyperalgesia in adjuvant rat pain model. Neuroscience. 2003;117(3):503-12.

43. Tóth A, Kedei N, Wang Y, Blumberg PM. Arachidonyl dopamine as a ligand for the vanilloid receptor VR1 of the rat. Life Sci. 2003 Jun 13;73(4):487-98.

44. Lee J, Lee J, Kang M, Shin M, Kim JM, Kang SU, Lim JO, Choi HK, Suh YG, Park HG, Oh U, Kim HD, Park YH, Ha HJ, Kim YH, Toth A, Wang Y, Tran R, Pearce LV, Lundberg DJ, Blumberg PM. N-(3-Acyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl] thiourea Analogues: Novel Potent and High Affinity Antagonists and Partial Antagonists of the Vanilloid Receptor. J Med Chem. 2003 Jul 3;46(14):3116-26.

45. Tóth A, Kedei N, Szabó T, Wang Y, Blumberg PM. Thapsigargin binds to and inhibits the cloned vanilloid receptor-1. Biochem Biophys Res Commun. 2002 May 3;293(2):777-82.

46. Huang C, Wang Y, Han JS, Wan Y. Characteristics of electroacupuncture-induced analgesia in mice: variation with strain, frequency, intensity and opioid involvement. Brain Res. 2002 Jul 26;945(1):20-5.

47. Tang XQ, Wang Y, Han JS, Wan Y. Adenovirus-mediated GDNF protects cultured motoneurons from glutamate injury. Neuroreport. 2001 Oct 8;12(14):3073-6.

48. Sun RQ, Zhao CS, Wang HJ, Jing Z, Wang W, Yang K, Wang Y, Chang JK, Han JS. Nocistatin, a peptide reversing acute and chronic morphine tolerance. Neuroreport. 2001 Jun 13;12(8):1789-92.

49. Fang M, Wang Y, Liu HX, Liu XS, Han JS. Decreased GDNF expression in dorsal spinal cord of unilateral arthritic rat. Neuroreport. 2000 Mar 20;11(4):737-41.

50. Zhao CS, Li BS, Zhao GY, Liu HX, Luo F, Wang Y, Tian JH, Chang JK, Han JS. Nocistatin reverses the effect of orphanin FQ/nociceptin in antagonizing morphine analgesia. Neuroreport. 1999 Feb 5;10(2):297-9.

51. Han Z, Jiang YH, Wan Y, Wang Y, Chang JK, Han JS. Endomorphin-1 mediates 2 Hz but not 100 Hz electroacupuncture analgesia in the rat. Neurosci Lett. 1999 Oct 22;274(2):75-8.



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