Chen Lab / CV & Publications

Curriculum Vitae - Shiming Chen, Ph.D.

Address:

Washington University School of Medicine
Department of Ophthalmology and Visual Sciences
660 S. Euclid Ave. Campus Box 8096
St. Louis, MO 63110
(314) 747-4350 office
(314) 747-4351 laboratory
(314) 747-4211 fax
chen@vision.wustl.edu

Present Positions:
  • Associate Professor of Ophthalmology and Visual Sciences,
    Associate Professor of Molecular Biology and Pharmacology
  • Washington University School of Medicine, St. Louis, MO

Education:
1978-1982

B.S. Biology, Capital Normal University, Beijing, China
1982-1984

M.S. Biochemistry, Beijing Medical University, Beijing, China Mentor: Pei-Nan Liu
1986-1992

Ph.D. Biochemistry and Molecular Biology, State University of New York-Upstate Medical University, Syracuse, NY. Mentor: Robert W. West, Jr.
1992-1998

Post-doctoral fellow, Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD. Mentor: Donald J. Zack

Academic Positions:
1998-2005

Assistant Professor of Ophthalmology and Visual Sciences
Instructor of Molecular Biology and Pharmacology
Washington University School of Medicine, St. Louis, MO
2005-present

Associate Professor of Ophthalmology and Visual Sciences
Associate Professor of Molecular Biology and Pharmacology
Washington University School of Medicine, St. Louis, MO

Honors and Awards:
1998

The Albert L. Lehninger Prize for Postdoctoral Investigation, Johns Hopkins University School of Medicine, Baltimore, MD
1998

Career Development Award, Research to Prevent Blindness.
2003

Sybil B. Harrington Scholar Award, Research to Prevent Blindness.

Editorial Activities:
1998-present

Reviewer for Proc Natl Acad Sci USA, Human Molecular Genetics, Journal of Biological Chemistry, Gene, Neurobiology of Disease, Investigative Ophthalmology & Visual Science, Experimental Eye Research, and Molecular Vision.

Consulting / Advisory Experience:
1999-2004

Ad hoc reviewer for Foundation Fighting Blindness, Inc., USA and Welcome Trust, London, UK.
2005

Ad hoc reviewer, Panel for Career Development Grant Applications, NEI, NIH ZEY1VSN(05).
2006

Ad hoc reviewer, Panel for the Biology and Diseases of the Posterior Eye (BDPE, formerly VISC), NIH/CSR.

Professional Societies and Organizations:
  • American Association for the Advancement of Science (AAAS)
  • Association for Research in Vision and Ophthalmology (ARVO)
  • American society for Biochemistry and Molecular Biology (ASBMB)
  • Academic Woman's Network at Washington Univ Sch of Med.

Professional and Departmental Activities:
2004-present

Member, Animal Studies Committee, Washington University.
2004-present

Coordinator for vision science seminar series, Department of Ophthalmology and Visual Sciences (DOVS)
2006-present

Member, Faculty Search Committee, DOVS.

Selected Publications:

  1. Deng G, Lu Y, Chen S, Miao J, Lu G, Li H, Cai H, Xu X, E Z, Liu P: Activated c-Ha-ras oncogene with a guanine to thymine transversion at the twelfth codon in a human stomach cancer cell line. Cancer Res 1987; 47:3195-3198.
  2. Chen S, Miao J, Cai H, Li H, Deng G, Liu P, Lu Y, Lu G, Xu X, E Z: Construction of the genomic library of the secondary transformants from human gastrocarcinoma cell line BGC-823 and molecular cloning of the transforming gene. Acta Genet Sinica 1987; 14:155-162. (Chinese with English abstract)
  3. West RW Jr, Chen S, Putz H, Bulter G, Banerjee M: GAL1-GAL10 divergent promoter region of Saccharomyces cerevisiae contains negative control elements in addition to functionally separate and possibly overlapping upstream activating sequences. Genes Develop 1987; 1:1181-1131.
  4. Finley RL, Chen S, Ma J, Byrne P, West RW Jr: Opposing regulatory functions of positive and negative control elements in UASG control transcription of the yeast GAL genes. Mol Cell Biol 1990; 10:5663-5670.
  5. Chen S, West RW Jr, Ma J, Johnson S, Gans H, Kruger B, Ma J: TSF3, a global regulatory protein that silences transcription of yeast GAL genes, also mediates repression by a2 repressor and is identical to SIN4. Mol Cell Biol 1993; 13:831-840.
  6. Chen S, West RW Jr, Ma J, Johnson S, Gans H, Woldehawariat G: TSF1 to TSF6, required for silencing the Saccharomyces cerevisiae GAL genes, are global regulatory genes. Genetics 1993; 134:701-716.
  7. Nie Z, Chen S, Kumar R, Zack DJ: RER, an evolutionarily conserved sequence upstream of the rhodopsin gene, has enhancer activity. J. Biol Chem 1996; 271:2667-2675.
  8. Chen S, Zack DJ: Ret 4, a positive acting rhodopsin regulatory element identified using a bovine retina in vitro transcription system. J Biol Chem 1996; 271:28549-28557.
  9. Kumar R, Chen S, Scheurer D, Wang Q-L, Dun E, Sung C-H, Rehemtulla A, Swaroop A, Adler R, Zack DJ: The bZIP transcription factor NRL stimulates rhodopsin promoter activity in primary retinal cell cultures. J Biol Chem 1996; 271:29612-29618.
  10. Chen S, Wang Q-L, Nie Z, Sun H, Lennon G, Copeland NG, Gilbert DJ, Jenkins NA, Zack DJ: Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 1997; 19:1017-1030.
  11. Swain PK, Chen S, Wang Q-L, Affatigato LM, Coats CL, Brady KD, Fishman GA, Jacobson SG, Swaroop A, Stone E, Sieving PA, Zack DJ: Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. Neuron 1997; 19:1329-1336.
  12. Li X, Chen S, Wang Q-L, Zack DJ, Snyder SH, Borjigin J: A pineal regulatory element (PIRE) mediates transactivation by the pineal/retina specific transcription factor, CRX. Proc Natl Acad Sci USA 1998; 95:1876-1881.
  13. Freund CL, Wang Q-L, Chen S, Muskat BL, Sheffield VC, Jacobson SG, McInnes RR, Zack DJ, Stone EM: De novo mutations in the CRX homeobox gene associated with Leber's congenital amaurosis. Nature Genetics 1998; 18:311-312.
  14. Swaroop A, Wang Q-L, Wu W, Cook J, Coats C, Xu S, Chen S, Zack DJ, Sieving PA: Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX:direct evidence for the involvement of CRX in the development of photoreceptor function. Hum Mol Genet. 1999; 8:299-305.
  15. Fei Y, Matragoon S, Smith SB, Overbeek PA, Chen S, Zack DJ, Liou GI: Functional dissection of the promoter of the interphotoreceptor retinoid-binding protein gene: the cone-rod-homeobox element is essential for photoreceptor-specific expression in vivo. J. Biochem (Tokyo) 1999;125:1189-1199.
  16. Chau K-Y, Chen S, Zack DJ, Ono SJ: Functional domains of the Cone rod homeobox (CRX) transcription factor. J. Biol. Chem. 2000; 275:37264-37270.
  17. Mitton KP, Swain PK, Chen S, Xu S, Zack DJ, and Swaroop A: The leucine zipper of Nrl interacts with the Crx-homeodomain: A possible mechanism of transcriptional synergy in rhodopsin regulation. J Biol Chem. 2000, 275:29794-29799.
  18. LaSpada AR, Fu YH, Sopher BL, Libby RT, Wang X, Li LY, Einum DD, Huang J, Possin DE, Smith AC, Martinez RA, Koszdin KL, Treuting PM, Ware CB, Hurley JB, Ptacek LJ, Chen S: Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron. 2001, 31:913-927. (Cover article)

    This article was selected for a Preview in the same issue of Neuron: Orr HT, "Qs in the nucleus" Neuron 2001, 31: 875-876.
  19. Mani SS, Batni S, Whitaker L, Chen S, Engbretson G, Knox BE: Xenopus rhodopsin promoter. Identification of immediate upstream sequences necessary for high level, rod-specific transcription. J Biol Chem 2001, 276:36557-36565.
  20. Ma GC, Wang TM, Su CY, Wang YL, Chen S and Tsai HJ: Retina-specific cis-elements and binding nuclear proteins of carp rhodopsin gene. FEBS Lett 2001, 508:265-271.
  21. *Chen S, Wang QL, X u S, Li LY, Liu I, Wang Y, and Zack DJ: Functional Analysis of Cone-Rod Homeobox (CRX) Mutations Associated with Retinal Dystrophy. Hum Mol Genet. 2002, 11:873-884.
    * Corresponding author.
  22. Dunaief JL, King A, Esumi N, Eagen M, Dentchev T, Sung C-H, Chen S and Zack DJ: Protein Phosphatase 1 binds strongly to the retinoblastoma protein but not to p107 or p130 in vitro and in vivo. Curr. Eye Res. 2002, 24:392-6.
  23. Wang X, Xu S, Rivolta C, Li LY, Peng G-H, Swain PK, Sung C-H, Swaroop A, Berson EL, Dryja TP, Chen S: Barrier-to-autointegration factor (Baf) interacts with the cone-rod homeobox (Crx) and represses its transactivation function. J Biol Chem. 2002, 277:43288-43300.
  24. Yoo S-Y, Pennesi ME, Weeber EJ, Xu B, Atkinson R, Chen S, Armstrong DL, Wu SM, Sweatt JD, and Zoghbi HY: SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity. Neuron 2003, 37:383-401.
  25. *Chen S, Peng G, Wang X, Smith AC, Grote SK, Sopher BL and La Spada AR: Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization. Hum Mol Genet. 2004, 13:53-67.
    *Corresponding author. (Cover article)
  26. Pittler SJ, Zhang Y, Chen S, Mears AJ, Zack DJ, Ren Z, Swain PK, Yao S, Swaroop A and White JB: Functional analysis of the rod photoreceptor cGMP phosphodiesterase alpha -subunit gene promoter: Nrl and Crx are required for full transcriptional activity. J. Biol. Chem. 2004, 279:19800-19807.
  27. Wang Q-L, Chen S, Esumi N, Swain PK, Haines HS, Peng G, Melia MB, McIntosh I, Heckenlively JR, Jacobson SG, Stone EM, Swaroop A and Zack DJ: QRX, a novel homeobox gene, modulates photoreceptor gene expression. Hum Mol Genet. 2004, 13:1025-1040.
  28. Rhee, KD, Goureau O, Chen S and Yang X-J: Cytokine-induced STAT3 activation in photoreceptor precursors regulates rod differentiation in the developing mouse retina. J. Neuroscience. 2004, 24:9779-9788.
  29. Peng G-H, O, Ahmad F, Liu J and Chen S: The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Hum Mol Genet. 2005, 14:747-764.
  30. Lerner LE, Peng G-H, Gribanova YE, Chen S, and Farber DB: Multiple Photoreceptor-Restricted Genes are Selectively Activated by the Sp4 Transcription Factor that Synergizes with CRX. J. Biol. Chem. 2005, 280:20642-20650.
  31. *Palhan V, *Chen S, Peng G-H, Tjernberg A, Chait BT, Fan Y, Gamper, AM, La Spada AR and Roeder RG: Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc Natl Acad Sci USA. 2005, 102:8472-8477.
    *These authors contributed equally to this work.
  32. Peng G-H and Chen S: Chromatin immunoprecipitation identifies photoreceptor transcription factor targets in mouse models of retinal degeneration: new findings and challenges. Visual Neuroscience. 2005, 22:575-586.
  33. Dorval KM, Bobechko BP, Fujieda H, Chen S, Zack DJ and Bremner R: Chx10 targets a subset of photoreceptor genes. J. Biol. Chem. 281:744-751, 2006.
  34. Hennig AK, Peng G-H and Chen S: Regulation of photoreceptor gene expression by Crx-associated transcription factor network. Brain Res. 2007, in press. 10.1016/j.brainres.2007.06.036 PMID: 17662965
  35. Peng G-H and Chen S: Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation. Hum. Mol. Genet. 2007, in press. PMID: 17656371

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