个人简介
B. S. 1989-1993, Shandong University, China;
M. S. 1993-1996, Dalian Institute of Chemical Physics, Chinese Academy of Sciences;
Ph. D. 1997-2001, Department of Chemistry, Washington University in St. Louis (Advisors:Professors Michael L. Gross and John-Stephen A. Taylor);
Assistant Professor in Chemistry, 2001-2005, University of California Riverside;
Associate Professor in Chemistry, 2005-2008, University of California Riverside;
Professor in Chemistry, 2008-present, University of California Riverside;
Donald T. Sawyer Endowed Founder's Chair in Chemistry, 2016-present, University of California Riverside;
Director, Environmental Toxicology Graduate Program, 2008-present, University of California Riverside
研究领域
DNA Damage and Mutagenesis
In this research area, our laboratory has been using a multi-pronged approach, encompassing mass spectrometry-based analytical chemistry, synthetic organic chemistry, biochemistry, molecular biology, and genetic tools to achieve a comprehensive understanding about the occurrene, repair and biological endpoints of DNA damage products. We aim to understand, at the molecular level, how structurally defined DNA lesions 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 DNA lesions induced by reactive oxygen species and alkylating agents. Students and postdocs working in this area are exposed to highly interdisciplinary training at the interface of chemistry and biology.
Proteomics
Our laboratory is equipped with five state-of-the-art mass spectrometers, including two Orbitraps (a Q Exactive Plus and an LTQ Orbitrap Velos). We also have access to an Orbitrap Fusion in the Institute for Integrated Genome biology and a TSQ Vantage triple-quadrupole in the Analytical Chemistry Instrumentation Facility. By taking advantage of these instruments, our research program in proteomics encompasses several different areas. In one area, we develop targeted quantitative proteomic methods, relying on multiple-reaction monitoring and parallel-reaction monitoring, for interrogating the human kinome, small GTPase proteome as well as other nucleotide- and metabolite-binding proteomes. We also empoly SILAC-based interaction screening for uncovering novel nucleic acid recognition proteins. Moreover, we are interested in uncovering novel protein players involved in the post-translational modifications of proteins and post-transcriptional regulations of RNA and in unraveling the mechanisms underlying the antineoplastic effects of the drugs and the cytotoxic effects of the environmental agents.
Epigenetics
In this area, we are interested in all aspects of epigenetic regulation of gene expression, including DNA methylation, post-translational modifications of histone proteins, and post-transcriptional modifications of RNA. In the latter aspect, we develop high-throughput LC-MS/MS-based method to quantify the global levels of modified ribonucleosides in RNA. We also employ proteomic tools, along with genetic manipulations (siRNA, shRNA, and genomic editing using CRISPR-Cas9), to uncover novel proteins involved in deposition, removal and recongition of modified nucleosides in RNA.
近期论文
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A Targeted Quantitative Proteomic Approach for Probing Altered Protein Expression of Small GTPases Associated with Colorectal Cancer Metastasis Huang, M.; Wang, Y.* Anal. Chem. 2019, in press.
Targeted Quantitative Kinome Analysis Identifies PRPS2 as a Promoter for Colorectal Cancer Metastasis Miao, W.; Wang Y.* J.Proteome Res. 2019, in press.
Location analysis of 8-oxo-7,8-dihydroguanine in DNA by polymerase-mediated differential coding. Tang, F.; Liu, S.; Li, Q.Y.; Yuan, J.; Li, L.; Wang, Y.; Yuan, B.F.;* Feng, Y. Chem. Sci., 2019, in press.
Human DNA polymerase η has reverse transcriptase activity in cellular environments. Su, Y.; Ghodke, P.P.; Egli, M.; Li, L.; Wang, Y. and Guengerich, F.P.* J. Biol. Chem., 2019, in press.
Cytotoxic and mutagenic properties of C1' and C3'-epimeric lesions of 2'-deoxyribonucleosides in human cells.Du, H.; Wang, P.; Li, L.; Amato, N.; Wang Y.* ACS Chem. Biol. 2019, 14, 478-485
Imatinib-induced changes in protein expression and ATP-binding affinities of kinases in chronic myelocytic leukemia cells.Miao, W.; Guo, L.; Wang Y.* Anal. Chem. 2019, 91, 3209-3214.
Dual regulation of Arabidopsis AGO2 by arginine methylation. Hu, P.; Zhao, H.; Zhu, P.; Xiao, Y.; Miao, W.; Wang, Y. and Jin, H.* Nat. Commun. 2019, 10, 844.
Quantification of DNA lesions induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in mammalian cells. Guo, S.; Leng, J.; Tan, Y.; Price, N. E. and Wang, Y.* Chem. Res. Toxicol., 2019, in press.
DNA replication studies of N-nitroso compound-induced O6-alkyl-2'-deoxyguanosine lesions in Escherichia coli.Wang, P.; Leng, J. and Wang, Y.* J. Biol. Chem. 2019, 294, 3894-3908.
Targeted profiling of heat shock proteome in radioresistant breast cancer cells.Miao, W.; Fan, M. Huang, M.; Li, J.J. and Wang, Y.* Chem. Res. Toxicol., 2019, 32, 326-332.
Integrated genomic and proteomic analyses reveal novel mechanisms of the methyltransferase SETD2 in renal cell carcinoma development.Li, L.; Miao, W.; Huang, M.; Williams, P. and Wang, Y.* Mol. Cell. Proteomics, 2019, 18, 437-447.
Normalized retention time for targeted analysis of the DNA adductome. Cui, Y.; Wang, P.; Yu, Y.; Yuan, J. and Wang, Y.* Anal. Chem., 2018, 90, 14111-14115.
N6-methyladenine DNA Modification in Glioblastoma Xie Q.; Wu, T.P.; Gimple, R.C.; Li, Z.; Prager, B.C.; Wu, Q.; Yu, Y.; Wang, P.; Wang Y.; Gorkin, D.U.; Zhang, C.; Dowiak, A.V.; Lin, K.; Zeng, C.; Sui, Y.; Kim, L.J.Y.; Miller, T.E.; Jiang, L.; Lee, C.H.; Huang, Z.; Fang, X.; Zhai, K.; Mack, S.C.; Sander, M.; Bao, S.; Kerstetter-Fogle, A.E.; Sloan, A.E.; Xiao, A.Z.*; Rich, J.N.* Cell, 2018, 175, 1228-1243.
Role of small GTPases in acquired tamoxifen resistance in MCF-7 cells revealed by targeted, quantitative proteomic analysis. Huang, M. and Wang, Y.* Anal. Chem. 2018, 90, 14551-14560.
Targeted quantitative profiling of GTP-binding proteins in cancer cells using isotope-coded GTP probes. Cai, R.; Huang, M. and Wang, Y.* Anal. Chem. 2018, 90, 14339-14346.
Identification of helicase proteins as clients for HSP90. Miao, W.; Li, L. and Wang, Y.* Anal. Chem., 2018, 90, 11751-11755.
Bypassing a 8,5-cyclo-2'-deoxyadenosine lesion by human DNA polymerase &eta at the atomic resolution. Weng, P.; Gao, Y.; Gregory, M.T.; Wang, P.; Wang, Y.* and Yang, W.* Proc. Natl. Acad. Sci. USA, 2018, 115, 10660-10665.
Pyruvate kinase M2 regulates homologous recombination-mediated DNA double-strand break repair. Sizemore, S.; Zhang, M.; Cho, J.H.; Sizemore, G.; Hurwitz, B.; Kaur, B.; Lehman, N.; Ostrowski, M.; Robe, P.; Miao, W.; Wang, Y.; Chakravarti, A. and Xia, F.* Cell Res., 2018, 28, 1090-1102.
Cytotoxic and mutagenic properties of O6-alkyl-2'-deoxyguanosine lesions in Escherichia coli cells. Wang, P. and Wang, Y.* J. Biol. Chem., 2018, 293, 15033-15042.
A novel malic acid-enhanced method for analysis of 5-methyl-2'-deoxycytidine, 5-hydroxymethyl-2'-deoxycytidine, 5-methylcytidine and 5-hydroxymethylcytidine in human urine using hydrophilic interaction liquid chromatography-tandem mass spectrometry. Guo, C.*; Xie, C.; Chen, Q.; Cao, X.; Guo, M.; Zheng, S. and Wang, Y.* Anal. Chim. Acta, 2018, 1034, 110-118.