Zhou-feng Chen, Ph.D.

Associate Professor of Anesthesiology
Washington University Pain Center
Basic Research Section

B.S. in Virology and Molecular Biology (1983)
Wuhan University, China

Ph.D. in Genetics (1994)
University of Texas Health Science Center, Houston

Postdoctoral training (1994-2000)
California Institute of Technology

chenz@wustl.edu

Chen Lab Web Page

Research in the Chen Lab is focused on the molecular mechanisms underlying the assembly of the spinal dorsal horn circuitry. The spinal dorsal horn is a pivotal center for integrating and relaying pain-sensing signals (nociceptive) from the periphery to the brain. We have shown that Drg11, a paired homeobox transcription factor, is important for the projection of cutaneous sensory afferents in the spinal cord and Drg11 knockout mice exhibited significantly reduced responses to noxious stimuli. To further understand the role of Drg11, we have identified several upstream regulators and downstream targets of Drg11. One of upstream genes is Lmx1b, a LIM homeobox-containing gene. Analysis of Lmx1b knockout mice revealed its essential role in the differentiation of dorsal horn cells and in the projections of nociceptive afferents. To complement the mouse knockout approach, we recently established a novel mouse in utero electroporation technique, which for the first time allows us to overexpress the genes in the dorsal spinal cord conveniently. In addition, we are using RNAi (RNA interference) technology, combined with in utero electroporation, to "knockdown" the genes of interest in the mouse dorsal spinal cord to assess their function.

Another area of focus is to identify the dorsal horn-specific genes by differential screening. A genome-wide microarray approach is being used to identify genes that may involve chronic pain and/or dorsal horn development. Cre/LoxP system is also being used to generate the dorsal spinal cord conditional knockouts. These molecular, cellular and genetic studies should not only gain insights into the fundamental mechanisms underlying the development of the dorsal spinal cord but also reveal potential sites of drug actions on central pain pathways and thus aid in the new pharmacological strategies for spinal cord injury and pain relief.

Zhao ZQ, Gao YJ, Sun YG, Zhao CS, Gereau RW. and Chen ZF . Opioid analgesia, morphine tolerance and morphine reward in mice lacking central serotonergic neurons. Proc. Natl. Acad. Sci. USA . 2007 104(36): 14519-24.

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

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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

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Wang CZ, Shi M, Yang LL, Yang RQ, Jacquin M, Chen ZF , and Ding YQ. Mesencephalic trigeminal nucleus development requires a paired homeodomain transcription factor, Drg11. Mol. Cell. Neurosci. 2007 35: 368-376.

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Guo C, Qiu HY, Huang Y, Chen HX, Yang RQ, Chen SD, Johnson R.L., Chen ZF, and Ding YQ. Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice. Development 2007, 134: 317-325

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Zhao, Z, Chiechio, S, Sun, Y, Zhang, K, Zhao, CS, Scott, M, Johnson, RL, Deneris, ES, Renner, KJ, Gereau, RW, and Chen, ZF (2007) Mice lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs. Journal of Neuroscience 27(22): 6045-6053.

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

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Zhao, Z.Q., Scott, M., Chiechio, S., Wang, J.-S., Renner, K.J., Gereau, R.W., Johnson, R.L., Deneris, E.S., and Chen, Z.F. (2006) Lmx1b is required for maintenance of central serotonergic neurons and mice lacking central serotonergic system show normal locomotor activity.  Journal of Neuroscience 26(49):12781-12788.

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Li MZ, Wang JS, Jiang DJ, Xiang CX, Wang FY, Zhang KH, Williams PR and Chen ZF (2006) Molecular mapping of developing dorsal horn-enriched genes by microarray and dorsal/ventral subtractive screening. Developmental Biology 292: 555-564.

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Erzurumlu RS, Chen ZF and Jacquin MF (2006) Molecular determinants of the face map development in the trigeminal brainstem. The Anatomical Record Part A 288A: 121-134.

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Wu LJ, Toyoda H, Zhao MG, Lee YS, Tang J, Ko S, Jia YG, Shum F Zerbinatti CV, Bu G, Wei F, Xu TL, Muglia L, Chen ZF, Auberson YP, Kaang BK and Zhuo M (2005) Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. The Journal of Neuroscience 25(48): 11107-11116.

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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 the spinal cord. Development 132: 2047-2056.

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Ding YQ, Xiang CX, and Chen ZF (2005) Generation and characterization of the PKCy-Cre Mouse Line. Genesis 43: 28-33.

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Dunston J, Reimschisel T, Ding YQ, Sweeney E, Johnson R, Chen ZF, and McIntosh I (2005) A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression.  European Jounal of Human Genetics 13(3): 330-5.

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Ren X, Ming G, Xie Y, Sun D, Zhao Z, Feng Z, Wang Q, Shim S, Chen ZF, Song H, Mei L and Xiong W. (2004) Focal adhesion kinase in netrin-1 signaling. Nature Neuroscience 7(11): 1204-12.

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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 cord. Development 131(15): 3693-3703.

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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 Neuroscience 23(19): 7246-54.

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Ding YQ, Marklund U, Yuan W, Yin J, Wegman L, Ericson J, Deneris E, Johnson RL, and Chen ZF (2003) Lmx1b is essential for the development of serotonergic neurons. Nature Neuroscience 6(9): 933-8.

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Wei F, Qiu CS, Kim SJ, Muglia L, Maas JW, Pineda VV, Xu HM, Chen ZF, Storm DR, Muglia LF, and Zhuo M (2002) Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases. Neuron 36(4): 713-26.

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Li YC, Kong J, Wei M, Chen ZF, Liu SQ,  and Cao, LP (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 110(2): 229-38.

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Chen ZF, Rebelo S, White F, Malmberg AB, Baba H, Lima D, Woolf CF, Basbaum AI, and Anderson DJ (2001) The paired homeodomain protein DRG11 is required for the projection of cutaneous sensory affernet fibers to the dorsal spinal cord. Neuron 31(1): 59-73.

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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. Nature Neuroscience 4(2): 164-9.

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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 Z, Bowers BJ, Boulter J, Wehner JM, Wehner JM, Lester HA (2001) Point mutant mice with hypersensitive (alpha) 4 nicotinic receptors show dopaminergic deficits and increased anxiety. Proc. Natl. Acad. Sci. USA 98:2786-91.

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Gunther T, Chen ZF, Kim J, Priemel M, Rueger JM, Amlin M, Moseley JM, Martin TJ, Anderson DJ, and Karsenty G (2000) Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature 409(6792): 199-203.

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