Leitlinien für Diagnostik und Therapie in der Neurologie Kopfschm erzen und andere Schm erzen Diagnostik und Therapie komplexer regionaler Schmerzsyndrome (CRPS) Entw icklungsstufe: S1 Stand: September 2012 AMWF-Registernum m er: 030/116 Univ.-Prof. Dr. Frank Birklein, Mainz Was gibt es Neues? Die klinischen Diagnosekriterien für das CRPS sind überprüft und von der internationalen Schmerzgesel schaft
Phs 398/2590 (rev. 06/09), biographical sketch format pageBIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES.
eRA COMMONS USER NAME (credential, e.g., agency login) chenzf EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) INSTITUTION AND LOCATION (if applicable) Wuhan University, China University of Texas Health Science Center, A. Personal Statement
My long-term interest is to understanding the molecular and cellular mechanisms of itch and pain sensations. Chronic itch is a major intractable clinical problem that is associated with a wide spectrum of skin diseases including atopic dermatitis, a very prevalent problem in children. My laboratory has identified the first itch-specific receptor, gastrin-releasing peptide receptor (GRPR), and neural circuits dedicated to the transmission of itch in the spinal cord. These findings have opened a new frontier for elucidating mechanisms of itch transmission from the skin to the brain as well as the relation between itch and pain. Our goal is to uncover novel targets for designing anti-itch therapy in the future. B. Positions and Honors
Professional Experience: 1983 – 1985 Practice Research Fellow, National Vaccine & Serum Institute, Beijing, China Assistant Research Fellow, National Vaccine & Serum Institute, Beijing, China Research Associate, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California Assistant Professor, Departments of Anesthesiology, Psychiatry and Developmental Biology, Washington University, St. Louis, Missouri Associate Professor, Departments of Anesthesiology, Psychiatry and Developmental Biology, Washington University, St. Louis, Missouri 2009 – present Professor, Departments of Anesthesiology, Psychiatry and Developmental Biology, Washington University, St. Louis, Missouri 2011 – present Director, Center for the Study of Itch, Washington University, St. Louis, Missouri Honors and Awards: 1986 State Education Committee Fellowship, China (to study abroad) John P. McGovern Award and First Place Winner, 11th Annual Graduate Student Research Symposium, GSBS, University of Texas Health Science Center at Houston Best Poster Award, Gordon Research Conference: Neural Development, Salve Regina University, and Newport, RI. 2010 Keynote speaker, Japanese biannual meeting on itch 2011 Founder and Director, Center for the Study of Itch Other experience and Professional memberships 2001- Member, The Society of Neuroscience 2001- Member, American Association for the Advancement of Science (AAAS) Ad Hoc reviewer for NIH study section ZRG1 IFCN-E, 2008; The NDPR study section, 2009. Ad Hoc reviewer for J. Clin Inv, Cell, Nature, Pain, Brain Res, Genesis, Development, Dev Dynam, Dev Biol, J. Neurosci, Trends Neurosci, Gene Dev, Eur J Neurosci, PNAS, ACTA Derm-Venereol, Exp Cell Res etc; Neuron, Nat Neurosci etc. International Reviewers for faculty performance, promotion and recruitment for various institutes including Institute of Neuroscience (China) and Peking-Tshinghua Center for life science (China) etc. C. Selected Peer-reviewed Publications (from more than 50 papers)
1. Chen ZF, Behringer RR: twist is required in head mesenchyme for cranial neural tube morphogenesis.
Genes Dev. 1995; 9:686-699
2. Ma Q, Chen ZF, del Barc Barrantes I, de la Pompa JL, Anderson DJ: neurogenin1 is essential for the
determination of neuronal precursors for proximal cranial sensory ganglia. Neuron 1998; 20:469-482
3. Wang HU, Chen ZF, Anderson DJ: Molecular distinction and angiogenic interaction between embryonic
arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 1998; 93:741-753
4. Chen ZF, Paquette AJ, Anderson DJ. NRSF/REST is required in vivo for repression of multiple neuronal
target genes in both neural and non-neuronal tissues during embryogenesis. Nat. Genet. 1998; 20:136-
5. Kin J, Jones BW, Zock C, Chen ZF, Wang H, Goodman CS, Anderson DJ: Isolation and characterization of
mammalian homologs of the Drosophila gene, glial cells missing. Proc. Natl. Acad. Sci. USA 1998;
6. Gerety SS, Wang HU, Chen ZF, Anderson DJ: Symmetrical mutant phenotype of th ereceptor EphB4 and
its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol. Cell 1999; 4:403-414
7. Chen ZF, Guenther T, Kin J, Prieme M, Rueger JM, Amling M, Moseley JM, Martin TJ, Anderson DJ,
Kensenty G: Genetic ablation of parathyroid glands by targeted mutation of Glial cells missing2 reveals an
auxiliary source of parathyroid hormone secretion. Nature 2000; 406:199-203
8. Wei F, Wang GD, Kerchner GA, Kim SJ, Xu HM, Chen ZF, Zhuo M: Genetic enhancement of
inflammatory pain by forebrain NR2B overexpression. Nat. Neurosci. 2001; 2:164-169
9. Labarca C, Schwarz J, Deshpande P, Schwarz S, Nowak MW, Fonck C, Nashmi R, Kofuji P, Dang H, Shi W, Fidan M, Khakh BS, Chen ZF, Bowers BJ, Boulter J, Wehner JM, Lester HA: Point mutant mice with
hypersensitive [alpha ] 4 nicotinic receptors show dopaminergic deficits and increased anxiety Proc. Natl.
Acad. Sci. USA 2001; 98:2786-2791
10. Chen ZF, Rebelo S, White F, Malmberg A, Baba B, Lima L, Woolf CJ, Basbaum AI, Anderson DJ: The
paired homeodomain protein DRG11 controls the projection of nociceptive sensory afferent fibers to the
dorsal spinal cord. Neuron 2001; 31:59-73
11. Wei F, Kim, SJ. Muglia. L, Maas. L, Pineda. VV, Xu. HM, Chen ZF, Storm DR, Muglia LJ and Zhuo M:
Elimination of inflammation related allodynia but not acute pain in mice lacking calmodulin stimulated
adenylyl cyclases. Neuron 2002; 36:713-726
12. Ding YQ, Yin J, Jacquin MF, and Chen ZF. Formation of whisker-related PrV-based lemniscal pathway
requires a paired homeodomain transcription factor, Drg11. J. Neurosci, 2003; 23:7426-7437
13. Ding YQ, Marklund U, Yuan W, Wegman L, Ericson J, Deneris E, Johnson RL, and Chen ZF. Lmx1b is
essential for the development of serotonergic neurons. Nat. Neurosci, 2003; 6:933-938
14. Ding YQ, Yin J, Artur K, Johnson RL, and Chen ZF. Lmx1b controls the differentiation and migration of the
superficial dorsal horn neurons of the spinal cord. Development 2004; 131:3693-703.
15. Ren XR, Ming GL, Xie Y, Hong Y, Sun DM, Zhao ZQ, Wang Q, Shim S, Chen ZF, Song HJ, Mei L and
Xiong WC. Focal adhesion kinase in netrin-1 signaling. Nat Naurosci. 2004. 7:1204-12.
16. Ding YQ, Kim JY, Rao Y, and Chen ZF. Ventral migration of early-born neurons requires Dcc and is
essential for the projections of primary afferents in the spinal cord. Development. 2005. 132: 2047-2056.
17. Wu LJ, Toyoda H, Zhao MG, Lee YS, Rang J, KO SW, Jia YH, Shum FWF, Zerbinatti CV, Bu G, Wei F, Xu TL, Muglia LJ, Chen ZF, Auberson YP, Kaang BK and Zhuo M. Upregulation of forebrain NMDA NR2B
receptors contributes to behavioral sensitization after inflammation. J. Neurosci. 2005, 25(48):11107-16.
18. Zhao ZQ, Scott M., Chiechio S, Wang JS, Renner K, Gereau R., Johnson R., Deneris E., and Chen ZF
Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic
system exhibit normal locomotor activity. J. Neurosci. 2006, 26: 12781-88.
19. Zhao ZQ, Chiechio S, Sun YG, Zhang KH, Zhao CS, Scott M, Johnson R., Deneris E., Renner K., Gereau RW. and Chen ZF Mice lacking central serotonergic neurons show enhanced inflammatory pain and an
impaired analgesic response to antidepressant drugs. J. Neurosci. 2007 27: 6045-6053
20. Sun YG, and Chen ZF. Gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord.
Nature 2007 448: 700-703 (This paper has received numerous international media coverage and
highlighted by Faculty of 1000, Nature and Science)
21. Zhao ZQ, Gao YJ, Sun YG, Zhao CS, Gereau RW. and Chen ZF. Central serotonergic neurons are
differentially required for opioid analgesia but not for morphine tolerance or morphine reward. Proc. Natl.
Acad. Sci. USA. 2007 104(36): 14519-24.
22. Jacquin MF, Joop JA. Xiang C, Shapiro LA, Ribak CE and Chen ZF. In Drg11 knockout mice, trigeminal
cell death is extensive, apoptotic and does not account for failed brainstem patterning. J. Neurosci. 2008
23. Hodges MR, Tattersall, GJ, Harris MB, McEvoy S, Richerson DN, Deneris ES, Johnson RL, Chen ZF,
Richerson GB. Defects in breathing and thermoregulation after genetic deletion of central serotonin
neurons. J. Neurosci. 2008 28: 2495-2505.
24. Sun YG, Gracias NG, Drobish J, Vasko MR, Gereau RW and Chen ZF. The c-kit signaling pathway is
required for the development of persistent pain. Pain, 144:178-186, 2009.
25. Sun YG, Zhao ZQ, Meng XL, Yin J and Chen ZF. Cellular basis of itch sensation. Science 325: 1531-
1534, 2009. This paper has received numerous international media coverage and highlighted by Faculty of 1000, Science and Nature) 26. Liu Q, Tang ZX, Surdenikova L, Kim SI, Patel KN, Kim A, Ru F, Guan Y, Weng H-J, Geng YX, Undem BJ, Kollarik M, Chen ZF, Anderson DJ and Dong XZ. Sensory neuron-specific GPCRs Mrgprs are itch
receptors mediating chloroquine-induced pruritus. Cell, 139(7): 1353-1365, 2009.
27. Lagerström MC, Rogoz K, Abrahamsen B Persson E, Reinius B, Nordenankar K, Ölund C, Smith C, Mendez JA, Chen ZF, Wood, JN, Mackenzie AW and Kullander K. VGLUT2 dependent sensory neurons in
the TRPV1 population regulate pain and itch. Neuron 68(3): 529-542, 2010.
28. Liu Y, Jiang Y-A, Si YX, Kim JY, Chen ZF and Rao Y. Molecular Regulation of Sexual Preference
Revealed by Genetic Studies of 5-HT in the Brain of Male Mice. Nature 472(7341): 95-99, 2011.
29. Liu XY, Liu ZC, Sun YG, Ross M, Kim SI, Tsai FF, Li QF, Jeffry J, Kim JY, Loh HH and Chen ZF.
Unidirectional cross activation of GRPR by MOR1D uncouples itch and analgesia-induced by opioids. Cell
147(2): 447-458, 2011 (This paper was highlighted by Cell with a preview, and by Nature's research highlight and Science's editor choice, and has been featured by Faculty of 1000)
30. Zhao ZQ, Huo FQ, Jeffry J, Hapmton L, Demehri S, Kim S, Liu XY, Barry DM, Wan L, Liu
ZC, Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey JF, Zhong J and Chen ZF.
Chronic itch development in sensory neurons requires BRAF signaling pathways. J. Clin
Invest. 123 (11), 4769-4780, 2013.
31. Liu ZX, Zhou JF, Li Y, Hu F, Lu Y, Ma M, Feng QR, Zhang J, Wang DQ, Zeng JW, Bao
JH, Kim JY, Chen ZF, Mestikawy S and L MM. Dorsal Raphe Neurons Signal Reward
through 5-HT and Glutamate. Neuron. 81(6): 1360-74, 2014
32. Zhao ZQ, Wan L, Liu XY, Huo FQ, Li H, Barry DM, Krieger S, Kim S, Liu ZC, Xu J,
Rogers BE, Li YQ, Chen ZF. Cross-Inhibition of NMBR and GRPR Signaling Maintains
Normal Histaminergic Itch Transmission. J Neurosci. 2014 Sep 10;34(37):12402-14.
33. Zhao ZQ, Liu XY, Jeffry J, Karunarathne WK, Li JL, Munanairi A, Zhou XY, Li H, Sun YG, Wan L, Wu ZY,
Kim S, Huo FQ, Mo P, Barry DM, Zhang CK, Kim JY, Gautam N, Renner KJ, Li YQ and Chen ZF.
Descending Control of Itch Transmission by the Serotonergic System via 5-HT1A-Facilitated GRP-GRPR
Signaling. Neuron. 2014 Nov 19 84(4):821-834. (This paper has received numerous world-wide media
coverage, including NBC nightly news, highlighted by Neuron as a video abstract and ABC etc).
34. Barry DMD, Li H, Liu XY, Shen KF, Liu XT, Wu ZY, Munanairi A, Chen XJ, Yin J, Sun
YG, Li YQ, Chen ZF. Critical Evaluation of the Expression of Gastrin Releasing Peptide
in Dorsal Root Ganglia and Spinal Cord Mol Pain 2016
35. Kim S, Barry, DM, Liu XY, Yin SJ, Karunarathne, WK, Munanairi A, Meng QT, Cheng W,
Mo P, Wan L, Yin J, Liu SB, Zhao ZQ, Gautam N., Zheng J, Chen, ZF. Facilitation
of TRPV4 by TRPV1 is required for itch transmission in sensory neurons. Science
Signaling 2016 (in revision)
D. Research Support
Ongoing Research Support
RO1 1R01AR056318-06 4/01/14-3/31/19
NIH/NIAMS Molecular mechanisms of the itch sensation in the spinal cord
R56 AR064294-01A1 9/15/14-6/30/16
NIH/NIAMS A novel approach to identify the mediators in chronic itch
R21 NS088861-01A1 2/1/2015 - 2/28/2017
NIH/NINDS The role of PKA in GRPR desensitization
R01NS094344 9/01/2015 - 06/30/2020
NIH/NINDS Understanding mechanisms that block GRPR-mediated chronic itch
R01 DA037261-01A1 10/01/2015 – 9/30/2020
NIH/NIDA Mechanism of desensitization of MOR1D-GRPR crosstalk
F. U.S. PATENT
US patent 7,939,071. 2011, "Artery- and vein-specific proteins and uses therefor", Inventors: Hai Wang, Zhou- Feng Chen, and David.J. Anderson. US patent 082267, 2008, "Compositions and methods for treating pruritus", Inventors: Zhou-Feng Chen and US patent 560,620, 2013"composition and methods for reducing opioid-induced pruritis", Inventors: Zhou-Feng Chen and Xianyu Liu
BOEHRINGER MANNHEIM / R-BIOPHARMEnzymatic BioAnalysis / Food Analysis UV-methodfor the determination of urea and ammonia in foodstuffs andother materials and for the determination of nitrogen after For in vitro use only Store at 2-8° C Kjeldahl-digestion (see pt. 12.2)Cat. No. 10 542 946 035Test-Combination for approx. 25 determinations each