Chen

Zhou-Feng Chen, PhD

Director, Center for the Study of Itch

Professor of Anesthesiology, Psychiatry and Developmental Biology


  Email Zhou-Feng Chen, PhD


Biography

Dr. Zhou-Feng Chen received his B.S. degree in virology from Wuhan University in 1983 and his Ph.D. Degree in mouse genetics from University of Texas Health Science Center at Houston in 1994, under the supervision of Prof. Richard Behringer.  After completing a postdoctoral training in Prof. David Anderson’s lab at Caltech, he joined the department of Anesthesiology as an assistant professor at Washington University School of Medicine in 2000 and became a full professor in 2009.  His research focuses on understanding of neural circuits of itch and pain with a wide range of interests including neuronal GPCR signaling in itch, descending and modulation and coding logics of itch and pain.  His team identified the first itch-specific receptor Gastrin-releasing peptide receptor (GRPR) and neural circuits in the spinal cord.  These seminal discoveries have opened up an exciting new frontier for deciphering itch circuits and function.  Ongoing research program is centered on signaling and synaptic mechanisms of itch transmission from the skin to the brain and crosstalk between itch and pain. Genetic and molecular tools are being developed to mark and isolate itch neurons for molecular, electrophysiological, cellular and circuit analysis. Detailed elucidation of how GRPR and/or GRPR neurons receive, process and relay itch information may shed insights onto potential therapies for chronic itch.


Cross-Inhibition of NMBR and GRPR Signaling Maintains Normal Histaminergic Itch Transmission.

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. J Neurosci. 2014 Sep 10;34(37):12402-14. 

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Postnatal maintenance of the 5-Ht1a-Pet1 autoregulatory loop by serotonin in the raphe nuclei of the brainstem.

Kim JY, Kim A, Zhao ZQ, Liu XY, Chen ZF. Mol Brain. 2014;7(1):48.

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Dorsal Raphe Neurons Signal Reward through 5-HT and Glutamate.

Liu Z, Zhou J, Li Y, Hu F, Lu Y, Ma M, Feng Q, Zhang JE, Wang D, Zeng J, Bao J, Kim JY, Chen ZF, El Mestikawy S, Luo M. Neuron. 2014; 81(6):1360-74.

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B-type natriuretic peptide is neither itch-specific nor functions upstream of the GRP-GRPR signaling pathway

Liu XY, Wan L, Huo FQ, Barry DM, Li H, Zhao ZQ and Chen ZF. Mol Pain. 2014; 10:4

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Chronic itch development in sensory neurons requires BRAF signaling pathways

Zhao ZQ*, Huo FQ*, Jeffry J, Hampton L, Demehri S, Kim S, Liu XY, Barry DM, Wan L, Liu ZC, Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey,…

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Over-Expression of the Gastrin-Releasing Peptide in Cutaneous Nerve Fibers and its Receptor in Spinal Cord in Primates with Chronic Itch.

Nattkemper LA, Zhao ZQ, Nichols AJ, Papoiu AD, Shively CA, Chen ZF, Yosipovitch G. J Invest Dermatol. 2013 Oct;133(10):2489-92

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The transcription factor, Lmx1b, promotes a neuronal glutamate phenotype and suppresses a GABA one in the embryonic trigeminal brainstem complex.

Xiang CX, Zhang KH, Johnson R.L., Jacquin M.F. and Chen ZF. The transcription factor, Lmx1b, promotes a neuronal glutamate phenotype and suppresses a GABA one in the embryonic trigeminal…

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Unidirectional cross activation of GRPR by MOR1D uncouples itch and analgesia-induced by opioids.

Liu XY, Liu ZC, Sun YG, Ross M, Kim SI, Tsai FF, Li QF, Jeffry J, Kim JY, Loh HH, and Chen ZF. (2011) Unidirectional cross activation of GRPR by…

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Itch Signaling in the nervous system.

Jeffry J, Kim SI, and Chen ZF. (2011) Itch Signaling in the nervous system. Physiology  26(4):286-292. PMID: 21841076

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Molecular regulation of sexual preference revealed by genetic studies of 5-HT in the brains of male mice.

Liu Y, Jiang Y-A, Si YX, Kim JY, Chen ZF, and Rao Y. (2011) Molecular regulation of sexual preference revealed by  genetic studies of 5-HT in the brains of…

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VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch.

Lagerström MC, Rogoz K, Abrahamsen B, Persson E, Reinius B, Nordenankar K, Ölund C, Simith C, Mendez JA, Chen ZF, Wood JN, Wallén-Mackenzie A, and Kullander K. (2010) VGLUT2-Dependent…

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The transcription factor, Lmx1b, is necessary for development of the principal trigeminal nucleus-based lemniscal pathway.

Xiang CX, Zhang K-H, Yin J, Arends JA, Erzurumlu RS, Jacquin MF, and Chen ZF. (2010) The transcription factor, Lmx1b, is necessary for development of the principal trigeminal nucleus-based…

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Sensory neuron-specific GPCRs Mrgprs are itch receptors mediating chloroquine-induced pruritus.

Liu Q, Tang Z, Surdenikova L, et al. Cell, 2009; 139: 1353-65.

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Cellular basis of itch sensation.

Sun YG*, Zhao ZQ*, Meng XL, Yin J, Liu XY, and Chen ZF. (2009) Cellular Basis of Itch Sensation. Science  325(5947): 1531-1534. (*equal contribution)   PMID: 19661382

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The c-kit signaling pathway is involved in the development of persistent pain.

Sun YG, Gracias NG, Drobish JK, Vasko MR, Gereau RW, and Chen ZF. (2009) The c-kit signaling pathway is involved in the development of persistent pain. Pain 144(1-2):178-186.  PMID:…

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REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells.

Jørgensen HF, Terry A, Beretta C, Pereira CF, Leleu M, Chen ZF, Kelly C, Merkenschlager M, and Fisher AG. (2009) REST selectively represses a subset of RE1-containing neuronal genes…

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Is REST required for ESC pluripotency.

Jørgensen HF, Chen ZF, Merkenschlager M, and Fisher AG. (2009) Is REST required for ESC pluripotency. Nature 457(7233): E4-E5.  PMID: 19242417

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Rest-Mediated regulation of extracellular matrix is crucial for neural development.

Sun Y-M, Cooper M, Finch S, Lin H-H, Chen ZF, Williams BP, and Buckley NJ. (2008) Rest-Mediated regulation of extracellular matrix is crucial for neural development. PLoS ONE 3(11):…

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Involvement of P311 in the affective, but not in the sensory component of pain.

Sun YG*, Gao YJ*, Zhao ZQ, Huang B, Yin J, Taylor GA, and Chen ZF. (2008) Involvement of P311 in the affective, but not in the sensory component of…

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In Drg11 knock-out mice, trigeminal cell death is extensive and does not account for failed brainstem patterning.

Jacquin MF, Joop JA. Xiang C, Shapiro LA, Ribak CE, and Chen ZF. (2008)  In Drg11 knock-out mice, trigeminal cell death is extensive and does not account for failed…

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Defects in breathing and thermoregulation in mice with near-complete absence of central serotonin neurons.

Hodges MR, Tattersall, GJ, Harris MB, McEvoy S, Richerson DN, Deneris ES, Johnson RL, Chen ZF, and Richerson GB. (2008) Defects in breathing and thermoregulation in mice with near-complete…

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Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward.

Zhao ZQ, Gao YJ, Sun YG, Zhao CS, Gereau RW., and Chen ZF. (2007) Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or…

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Gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord.

Sun YG, and Chen ZF. (2007) Gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature 448(7154): 700-703. PMID: 17653196

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Development of the mesencephalic trigeminal nucleus requires a paired homeodomain transcription factor, Drg11.

Wang CZ, Shi M, Yang LL, Yang RQ,Luo ZG, Jacquin MF, Chen ZF, and Ding YQ. (2007) Development of the mesencephalic trigeminal nucleus requires a paired homeodomain transcription factor,…

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Mice lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs.

Zhao ZQ, Chiechio S, Sun YG, Zhang KH, Zhao CS, Scott M, Johnson R., Deneris E., Renner K., Gereau RW., and Chen ZF.(2007) Mice lacking central serotonergic neurons show…

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Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice.

Guo C, Qiu HY, Huang Y, Chen HX, Yang RQ, Chen SD, Johnson R.L., Chen ZF, and Ding YQ. (2007) Lmx1b is essential for Fgf8 and Wnt1 expression in…

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Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system exhibit normal locomotor activity.

Zhao ZQ, Scott M., Chiechio S, Wang JS, Renner K, Gereau RW., Johnson R., Deneris E., and Chen ZF. (2006) Lmx1b is required for maintenance of central serotonergic neurons…

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Involvement of DRG11 in the development of the primary afferent nociceptive system.

Rebelo S, Chen ZF, Anderson DJ, and Lima D. (2006) Involvement of DRG11 in the development of the primary afferent nociceptive system Mol. Cell. Neurosci. 33(3): 236-246. PMID: 16978876

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Molecular mapping of developing dorsal horn-enriched genes by microarray and dorsal/ventral subtractive screening.

Li MZ, Wang JS, Jiang DJ,  Xiang CX, Wang FY, Zhang KH, Williams R.P., and Chen ZF. (2006) Molecular mapping of developing dorsal horn-enriched genes by microarray and dorsal/ventral…

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Molecular determinants of the face map development in the trigeminal brainstem.

Erzurumlu RS, Chen ZF, and Jacquin MF.  (2006) Molecular determinants of the face map development in the trigeminal brainstem. Anat Rec.  288(2): 121-134. PMID: 16432893

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Transcriptional control of the serotonergic neuronal development.

Chen ZF and Ding YQ. Transcriptional control of the serotonergic neuronal development.(2006) In  "Transcription factors in nervous system" Thiel G (Ed.), Wiley-VCH , Weinheim, pp. 143-156.

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Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation.

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…

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Generation and characterization of the PKCγ-Cre mouse line.

Ding YQ, Xiang CX, and Chen ZF. (2005) Generation and characterization of the PKCγ-Cre mouse line. Genesis  43(1): 28-33. PMID: 16106361

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Ventral migration of early-born neurons requires DCC and is essential for the projections of primary afferents in the spinal cord.

Ding YQ, Kim JY, Xu YS, Rao Y, and Chen ZF. (2005) Ventral migration of early-born neurons requires DCC and is essential for the projections of primary afferents in…

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A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression.

Dunston JA, Reimschisel T, Ding YQ, Sweeney E, Johnson RL, Chen ZF, and McIntosh I. (2005) A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of…

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Focal adhesion kinase in netrin-1 signaling.

Ren XR, Ming GL, Xie Y, Hong Y, Sun DM, Zhao ZQ, Feng Z, Wang Q, Shim S, Chen ZF, Song HJ, Mei L, and Xiong WC. (2004) Focal…

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Lmx1b controls the differentiation and migration of the superficial dorsal horn neurons of the spinal cord.

Ding YQ, Yin J, Kania A, Zhao ZQ, Johnson RL, and Chen ZF. (2004) Lmx1b controls the differentiation and migration of the superficial dorsal horn neurons of  the spinal…

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Lmx1b is essential for the development of serotonergic neurons.

Ding YQ, Marklund U, Yuan W, Yin J, Wegman L, Ericson Johan, Deneris E, Johnson RL, and Chen ZF. (2003) Lmx1b is essential for the development of serotonergic neurons. Nat.…

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Formation of whisker-related principal sensory nucleus-based lemniscal pathway requires a paired homeodomain transcription factor, Drg11.

Ding YQ, Yin J, Xu HM, Jacquin MF, and Chen ZF. (2003) Formation of whisker-related principal sensory nucleus-based lemniscal pathway requires a paired homeodomain transcription factor, Drg11. J. Neurosci.…

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Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases.

Wei F, Qiu C, Kim SJ, Muglia L, Maas JW, Pineda VV, Xu HM, Chen ZF, Storm DR, Muglia LJ, and Zhuo M. (2002) Genetic elimination of behavioral sensitization…

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1,25-dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system.

Li YC, Kong J, Wei M, Chen ZF, Liu SQ, and Cao LP. (2002) 1,25-dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J. Clin Invest.  110(2):…

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The paired homeodomain protein DRG11 is required for the projection of cutaneous sensory afferent fibers to the dorsal spinal cord.

Chen ZF, Rebelo S, White F, Malmberg AB, Baba H, Lima D, Woolf CJ, Basbaum AI, and Anderson DJ. (2001) The paired homeodomain protein DRG11 is required for the…

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Point mutant mice with hypersensitive [alpha ] 4 nicotinic receptors show dopaminergic deficits and increased anxiety.

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…

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Genetic enhancement of inflammatory pain by forebrain NR2B overexpression.

Wei F, Wang GD, Kerchner GA, Kim SJ, Xu HM, Chen ZF, and Zhuo M. (2001) Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Nat. Neurosci.  4(2): 164-169.…

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Genetic ablation of parathyroid glands by targeted mutation of Glial cells missing2 reveals an auxiliary source of parathyroid hormone secretion.

Gunther T*, Chen ZF*, Kim J, Priemel M, Rueger JM, Amling M, Moseley JM, Martin TJ, Anderson DJ, and Karsenty G. (2000) Genetic ablation of parathyroid glands by targeted…

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Symmetrical mutant phenotype of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development.

Gerety SS, Wang HU, Chen ZF, and Anderson DJ. (1999) Symmetrical mutant phenotype of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol. Cell  4(3):…

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NRSF/REST is required in vivo for repression of multiple neuronal target genes in both neural and non-neuronal tissues during embryogenesis.

Chen ZF, Paquette AJ, and Anderson DJ. (1998) NRSF/REST is required in vivo for repression of multiple neuronal target genes in both neural and non-neuronal tissues during embryogenesis. Nat.…

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Isolation and characterization of mammalian homologs of the Drosophila gene, glial cells missing.

Kim J, Jones BW, Zock C, Chen ZF, Wang H, Goodman CS, and Anderson DJ. (1998) Isolation and characterization of mammalian homologs of the Drosophila gene, glial cells missing.…

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Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4.

Wang HU, Chen ZF, and Anderson DJ. (1998) Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell   93(5): 741-753.  PMID:…

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Neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia.

Ma QF, Chen ZF, Barrantes IB, Pompa J, and Anderson DJ. (1998) Neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia. Neuron  20(3): 469-482.…

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Twist is required in head mesenchyme for cranial neural tube morphogenesis.

Chen ZF, and Behringer RR. (1995)  Twist is required in head mesenchyme for cranial neural tube morphogenesis. Genes Dev. 9(6): 686-699. PMID: 7729687

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New research explains why scratching makes you itch more

In a new study published in Neuron, Dr. Zhou-Feng Chen’s team explains why scratching may make you itch more.  Although the purpose of scratching is to produce pain to inhibit itch, the brain, when sensing pain signal, produces more serotonin to control pain.  Unexpectedly, Chen’s team found that serotonin also activates itch receptor called GRPR in the spinal cord to enhance itch transmission, resulting in more urge to scratch harder to inhibit itch; However, more serotonin release, while resulting in…

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New study uncovers a novel mechanism that maintains histaminergic itch.

In a new study, Chen’s lab has identified NMBR as a novel itch receptor for mediating histaminergic itch in the spinal cord.  Using a combination of pharmacological, behavioral and genetic approaches, the study delineates the respective roles for GRPR and NMBR in itch transmission.   The study reveals that NMB, an endogenous ligand for NMBR, exclusively activates NMBR, and additionally acts as a functional antagonist for GRPR.   In contrast, GRP, a cognate ligand for GRPR, activates both GRPR and NMBR in…

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New York Times Features Innovative Research at CSI

In a recent interview with The New York Times, Drs. Zhou-Feng Chen and Lynn Cornelius, talk about chronic itch as an unmet need and the clinical implication of the discovery of an itch-specific receptor called GRPR.

Read The New York Time article "Itching: more than deep-skin".

 

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A new study questions the existence of the BNP-NPRA-GRP-GRPR dedicated neuronal pathway for itch

A new study from Dr. Zhou-Feng Chen's laboratory shows that the BNP-NPRA signaling does not function upstream of the GRP-GRPR pathway. A NIH team recently proposed that B-type natriuretic peptide (BNP) but not GRP functions in pruriceptors, and BNP-NPRA acts upstream of the GRP-GRPR signaling pathway dedicated to itch (Reports, Science, May 24, 2013).  Chen's team provides comprehensive evidence supporting the notion that GRP is indeed an itch-specific peptide in pruriceptors. By contrast, BNP protein appears to be expressed in…

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Scientists unravel mechanisms in chronic itching

Anyone who has suffered through sleepless nights due to uncontrollable itching knows that not all itching is the same. New research at Washington University School of Medicine in St. Louis explains why.

Working in mice, the scientists have shown that chronic itching, which can occur in many medical conditions, from eczema and psoriasis to kidney failure and liver disease, is different from the fleeting urge to scratch a mosquito bite.

(Watch Youtube Video for this news)

That’s because chronic…

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