个人简介

Shandong University, China - B.S. (1993) Dalian Institute of Chemical Physics, China - M.S. (1996) Washington University, St. Louis - Ph.D. (2001) Chemical Research in Toxicology Young Investigator Award, 2012 AAAS Fellow, 2011 ASMS Research Award, 2005

研究领域

Analytical Chemistry/Chemical Biology

Research in the Wang group is concentrated on two broadly defined areas, DNA damage/mutagenesis and proteomics. In the DNA damage and mutagenesis area, our laboratory has been using a multi-pronged approach, which encompasses mass spectrometry-based analytical chemistry, synthetic organic chemistry, biochemistry and molecular biology tools to understand, at the molecular level, how various DNA damage products are repaired, and how they perturb the efficiency and fidelity of flow of genetic information during DNA replication and transcription. The types of DNA damage that we have been working with include bulky DNA lesions induced by reactive oxygen species and, more recently, the carboxyalkylated DNA lesions induced by methylglyoxal (a byproduct of glycolysis) and metabolites of N-nitroso compounds formed endogenously or present in environmental pollutants. Students and postdocs working in this area are exposed to highly interdisciplinary training at the interface of chemistry and biology. In the proteomics area, we focus on three different aspects: Quantitative Proteomics. We employ Stable Isotope Labeling by Amino Acid in Cell Culture (SILAC) combined with LC-MS/MS to assess, at the global proteome level, the perturbation in expression of proteins in cells that are treated with anti-cancer drugs and environmental agents. The objectives for these studies are to unravel the mechanisms underlying the anti-neoplastic effects of the drugs and the cytotoxic effects of the environmental agents. Post-translational Modifications of Proteins. We employ mass spectrometry to identify novel post-translational modifications of cellular proteins and use molecular biology tools to assess the biological significances of these modifications. Functional Proteomics. We design chemical probes to selectively enrich and pull-down membrane and nucleotide-binding proteins from the entire proteome and examine how these subset of proteomes respond to extracellular stimulants. Students and postdocs working in this area have access to state-of-the-art instrumentation (including a Thermo LTQ Orbitrap Velos with nano-LC and an Agilent 6510 Q-TOF with chip-cube interface) in the group and are exposed to a variety of other experimental techniques including mammalian cell culture and molecular biology.

近期论文

查看导师新发文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Liang, Q.; Dexheimer, T.S.; Zhang, P.; Rosenthal, A.S.; Villamil, M.A.; You, C.; Zhang, Q.; Chen, J.; Sun, H.; Luci, D.K.; Yuan, B.; Simeonov, A.; Jadhav, A.; Xiao, H.; Wang, Y.; Maloney, D.J.*; Zhuang, Z. A selective USP1/UAF1 inhibitor links deubiquitination to DNA damage responses. Nat. Chem. Biol., 2014, 10, 298-304. Xiao, Y.; Guo, L.; Wang, Y.* A targeted quantitative proteomics strategy for global kinome profiling of cancer cells and tissues. Mol. Cell. Proteomics, 2014, 13, 1065-1075. Wang, P.; Williams, R.T.; Guerrero, C.R.; Ji, D.; Wang, Y.* Fragmentation of electrospray-produced deprotonated ions of oligodeoxyribonucleotides containing an alkylated or oxidized thymidine. J. Am. Soc. Mass Spectrom., 2014, 25, 1067-1076. Price, N.E.; Johnson, K.M.; Wang, J.; Fekry, M.I.; Wang, Y. and Gates, K.S.* Interstrand DNA-DNA cross-link formation between adenine residues and abasic sites in duplex DNA. J. Am. Chem. Soc. 2014, 136, 3483-3490. Guo, L.; Xiao, Y. and Wang, Y.* Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblast cells. Toxicol. Appl. Pharmacol., 2014, 277, 21-29. Amato, N.; Wang, Y.* Epimeric DNA lesions: Products from the improper chemical repair of 2-deoxyribose radicals. Chem. Res. Toxicol. 2014, 27, 470-479. Haque, M. M.; Sun, H.; Liu, S.; Wang, Y. and Peng, X.* Photo-switchable DNA interstrand cross-Link formation by a coumarin-modified nucleotide. Angew. Chem. Int. Ed., 2014, 53, 7001-7005. Prins, J.M.; Fu, L.; Guo, L. and Wang, Y.* Cd2+-induced alteration of global proteome of human skin fibroblast cells. J. Proteome Res., 2014, 13, 1677-1687. Zhai, Q.; Wang, P. and Wang, Y.* Cytotoxic and mutagenic properties of regioisomeric O2-, N3- and O4-ethylthymidines in bacterial cells. Carcinogenesis, 2014, 35, 2002-2006. Xiao, Y.; Guo, L. and Wang, Y.* Comprehensive characterization of SGTP-binding proteins by orthogonal quantitative SGTP-affinity profiling and SGTP/GTP competition assays. Anal. Chem., 2014, 86, 4550-4558. Ji, D.; Lin, K.; Song, J. and Wang, Y.* Effects of Tet-induced oxidation products of 5-methylcytosine on Dnmt1- and DNMT3a-mediated cytosine methylation. Mol. Biosyst., 2014, 10, 1749-1752. Cai, Q.; Fu, L.; Wang, Z.; Gan, N.; Dai, X. and Wang, Y.* a-N-methylation of damaged DNA-binding protein 2 (DDB2) and its function in nucleotide excision repair. J. Biol. Chem., 2014, 289, 16046-16056. Bullard, W.; da Rosa-Spiegler, J.L.; Liu, S.; Wang, Y. and Sabatini, R.* Identification of the glucosyltransferase that converts hydroxymethyluracil to base J in the trypanosomatid genome. J. Biol. Chem., 2014, 289, 20273-20282. Fu, L.; Guerrero, C.R.; Zhong, N.; Niedernhofer, L.J.; Pfeifer, G.P.; Xu, G.-L.; Wang, Y.* Tet-mediated formation of 5-hydroxymethylcytosine in RNA. J. Am. Chem. Soc., 2014, 136, 11582-11585. Ji, D. and Wang, Y.* Facile enzymatic synthesis of base J-containing oligodeoxyribonucleotides and an analysis of the impact of base J on DNA replication in cells. PLoS One, 2014, 9, e103335. Liu, S.; Ji, D.; Cliffe, L.; Bullard, W.; Sabatini, R. and Wang, Y.* Quantitative mass spectrometry-based analysis of β-D-glucosyl-5-hydroxymethyluracil in genomic DNA of Trypanosoma brucei. J. Am. Soc. Mass Spectrom., 2014, in press. Ji, D.; You, C.; Wang, P. and Wang, Y.* Effects of Tet-induced oxidation products of 5-methylcytosine on DNA replication in mammalian cells. Chem. Res. Toxicol., 2014, 27, 1304-1309. Zhai, Q.; Wang, P.; Cai, Q. and Wang, Y.* Syntheses and characterizations of the in-vivo replicative bypass and mutagenic properties of the minor-groove O2-alkylthymidine lesions. Nucleic Acids Res., 2014, in press. Xiao, Y. and Wang, Y.* Global discovery of protein kinases and other nucleotide-binding proteins by mass spectrometry. Mass Spectrom. Rev., 2014, in press. Zhang, F.; Paramasivam, M.; Cai, Q.; Dai, X.; Wang, P.; Lin, K.; S, J.; Seidman, M.M. and Wang, Y.* Arsenite binds to the RING finger domains of RNF20-RNF40 histone E3 ubiquitin ligase and inhibits DNA double-strand break repair. J. Am. Chem. Soc., 2014, 136, in press. Johnson, K.; Price, N.; Wang, J.; Fekry, M.; Dutta, S.; Seiner, D.; Wang, Y.; Gates, K. S.* On the formation and properties of interstrand DNA-DNA cross-links forged by reaction of an abasic site with the opposing guanine residue of 5’-CAp sequences in duplex DNA. J. Am. Chem. Soc., 2013, 135, 1015-1025. Williams, R.T.; Nalbandian, J.; Tu, A.; Wang, Y.* Nuclease digestion and mass spectrometric characterization of oligodeoxyribonucleotides containing 1,2-GpG, 1,2-ApG, and 1,3-GpXpG cisplatin intrastrand cross-links. Clin. Chim. Acta, 2013, 420, 160-170. Prins, J.M. and Wang, Y.* Quantitative proteomic analysis revealed N’-nitrosonornicotine-induced down-regulation of non-muscle myosin II and reduced cell migration in cultured human skin fibroblast cells. J. Proteome Res., 2013, 12, 1282-1288. Xiao, Y.; Guo, L.; Jiang, X.; Wang, Y.* Proteome-wide discovery and characterizations of nucleotide-binding proteins with affinity-labeled chemical probes. Anal. Chem., 2013, 85, 3198-3206. Chen, M.-L.; Shen, F.; Huang, W.; Qi-J.-H.; Wang, Y.; Feng, Y.-Q.*; Liu, S.-M.* and Yuan, B.-F.* Quantification of 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from hepatocellular carcinoma tissues by capillary hydrophilic-interaction liquid chromatography/quadrupole TOF mass spectrometry. Clin. Chem., 2013, 59, 824-832. Liu, S.; Wang, J.; Su, Y.; Guerrero, C.; Zeng, Y.; Mitra, D.; Brooks, P.J.; Fisher, D.E.; Song, H. and Wang, Y.* Quantitative assessment of Tet-induced oxidation products of 5-methylcytosine in cellular and tissue DNA. Nucleic Acids Res., 2013, 41, 6421-6429. Ghang, Y.J.; Schramm, M.P.; Zhang, F.; Acey, R.; David, C.; Wilson, E.; Wang, Y.; Cheng, Q. and Hooley, R. J.* Selective cavitand-mediated endocytosis of imaging agents. J. Am. Chem. Soc., 2013, 135, 7090-7093. Guo, L.; Xiao, Y. and Wang, Y.* Hexavalent chromium-induced alteration of proteomic landscape in human skin fibroblast cells. J. Proteome Res., 2013, 12, 3511-3518. Wen, L.; Chen, Z.; Zhang, F.; Cui, X.; Sun, W.; Geary, G.G.; Wang, Y.; Johnson, D.A.; Chien, S.*; Zhu, Y.* and Shyy, J. Y-J.* CaMKKb phosphorylation of SIRT1 in endothelium is athero-protective. Proc. Natl. Acad. Sci. USA, 2013, 110, E2420-E2427. Liu, S. and Wang, Y.* A Quantitative mass spectrometry-based approach for assessing the repair of 8-methoxypsoralen-induced DNA interstrand crosslink and monoadducts in mammalian cells. Anal. Chem., 2013, 85, 6732-6739. Xiao, Y.; Guo, L. and Wang, Y.* Isotope-coded ATP probe for quantitative affinity profiling of ATP-binding proteins. Anal. Chem., 2013, 82, 7478-7486. Dai, X.; Otake, K.; You, C.; Cai, Q.; Wang, Z.; Masumoto, H. and Wang, Y.* Identification and functional characterization of a-N-methylation of CENP-B. J. Proteome Res., 2013, 12, 4167-4175. You, C.; Swanson, A. L.; Dai, X.; Yuan, B.; Wang, J. and Wang, Y.* Translesion synthesis of 8,5’-cyclopurine-2’-deoxynucleosides in vitro and in human cells. J. Biol. Chem., 2013, 288, 28548-28556. Guerrero, C. R.; Wang, J. and Wang, Y.* Induction of 8,5’-cyclopurine-2’-deoxynucleosides in isolated DNA by Fenton-type reagents. Chem. Res. Toxicol., 2013, 26, 1361-1366. Huang, J.; Liu, S.; Bellani, M.; Thazhuthaveetil, A.K.; Ling, C.; de Winter, J.; Wang, Y.; Wang, W. and Seidman, M.M.* Faconi anemia protein M mediates replication traverse of DNA interstrand crosslinks. Mol. Cell, 2013, 52, 434-446. Xing, X.-W,; Liu, Y.-L.; Vargas, M.; Wang, Y.; Feng, Y.-Q.; Zhou, X.*; Yuan, B.-F.* Mutagenic and cytotoxic properties of oxidized products of 5-methylcytosine revealed by next-generation sequencing. PLoS ONE, 2013, 8, e72993. Zhang, F.; Fu, L. and Wang, Y.* 6-Thioguanine induces mitochondrial dysfunction and oxidative DNA damage in acute lymphoblastic leukemia cells. Mol. Cell. Proteomics, 2013, 12, 3803-3811. Ponts, N.; Fu, L.; Harris, E. Y.; Zhang, J.; Chung, D.-W. D.; Cervantes, M.C.; Prudhomme, J.; Atanasova-Penichon, V.; Zehraoui, E.; Bunnik, E.; Rodrigues, E.M.; Lonardi, S.; Hicks, G.R.; Wang, Y.; Le Roch, K.G.* Genome-scale discovery of DNA methylations in the human malaria parasite. Cell Host Microbe, 2013, 14, 696-706. Andersen, N.; Wang, P. and Wang, Y.* Replication across regioisomeric ethylated thymidine lesions by purified DNA polymerases. Chem. Res. Toxicol., 2013, 26, 1730-1738. Liu, S.; Dunwell, T.L.; Pfeifer, G.P.; Dunwell, J.D. and Wang, Y.* Detection of oxidation products of 5-methyl-2'-deoxycytidine in Arabidopsis DNA. PLoS ONE, 2013, 8, e84620.