2022-09-06T10:50:17+08:002019-12-03|
Contact Information
Research Team
Name Position Office Phone Email
Wenfei PANPhD Student (Lab Representative)yb87628@um.edu.mo
Lingfeng TANGPhD Student
Chengjian FANPhD Student
Xinyu MIAOPhD Student
Education
PhD Department of Chemistry and Biochemistry, University of California San Diego, USA (2011)
MSc Department of Chemistry and Biochemistry, University of California San Diego, USA (2008)
BSc Department of Chemistry and Biochemistry, University of California San Diego, USA (2005)
Positions
08/2022 – Present Associate Professor, Faculty of Health Sciences, University of Macau
08/2016 – 08/2022 Assistant Professor, Faculty of Health Sciences, University of Macau
09/2015 – 08/2016 Visiting Assistant Professor, Faculty of Health Sciences, University of Macau
03/2015 – 08/2015 Visiting Scientist, Department of Chemistry and Biochemistry, University of California San Diego, USA
09/2012 – 03/2015 Postdoc Research Fellow, Department of Biological Sciences, Columbia University, New York, USA
07/2011 – 09/2012 Postdoc Research Fellow, Department of Chemistry and Biochemistry, University of California San Diego, USA
Research Interests
In this laboratory we use our knowledge and experience in the area of biochemistry, structural biology, cellular and molecular biology to study the functions and mechanisms of important molecules focusing on their biological functions. The major focus of the current research involves understanding the signal transduction mediated by the nuclear factor kappaB (NF-kB) and IkB proteins. The mammalian Rel/NF-kB family of transcription factors plays a critical role in diverse physiological processes including the immune response, inflammation, cell proliferation and survival. A wide variety of signals activate NF-kB driven gene expression through different NF-kB signaling pathways in a stimulus- and cell type-dependent manner. Due to the diverse regulatory mechanisms acting on NF-kB, the signal dependent activation of NF-kB remains a challenging area of research. Using both biochemical and structural approaches, we will determine how post-translational modifications, e.g. phosphorylation, affect NF-kB:IkB:DNA complex formation, binding specificity, and target gene expression.
Representative Publications
  1. Lin, G. W., Xu, C. G., Chen, K., Huang, H. Q., Chen, J. P., Song, B., Chan, J. K. C., Li, W. Y., Liu, W. P., Shih, L. Y., Chuang, W. Y., Kim, W. S., Tan, W., Peng, R. J., Laurensia, Y., Cheah, D. M. Z., Huang, D. C., Cheng, C. L., Su, Y.-J., Tan, S. Y., Ng, S. B., Tang, T. P. L., Han, K. D., Wang, V.Y., Jia, W. H., Pei, Z., Li, Y. J., Gao, S., Shi, Y. Y., Hu, Z. B., Zhang, F., Zhang, B., Zeng, Y. X., Shen, H. B., He, L., Ong, C. K., Lim, S. T., Chanock, S., Kwong, Y. L., Lin, D., Rothman, N., Khor, C. C., Lan, Q., and Bei, J. X. Genetic Risk of Extranodal Natural Killer T-Cell Lymphoma: A Genome-Wide Association Study in Multiple Populations. Lancet Oncol. 2020, 21 (2), 306-316. DOI: https://doi.org/10.1016/S1470-2045(19)30799-5
  2. Mulero, M.C.*, Wang, V.Y.*, Huxford, T, Ghosh, G. Genome reading by the NF-κB transcription factors. Nucleic Acids Res2019, 47(19), 9967-9989. DOI: https://doi.org/10.1093/nar/gkz739 (Co-first author)
  3. Kwasnik, A.*, Wang, V.Y.*,Krzyszton, M., Gozdek, A., Zakrzewska-Placzek, M., Stepniak, K., Poznanski, J., Tong, L., and Kufel, J., Arabidopsis DXO1 links RNA turnover and chloroplast function independently of its enzymatic activity. Nucleic Acids Res2019, 47(9), 4751-4764. http://doi.org/10.1093/nar/gkz100 (Co-first author)
  4. Meng, Y., Ren, Z., Xu, F., Zhou, X., Song, C., Wang, V.Y.,Liu, W., Lu, L., Thomson, J.A., Chen, G. Nicotinamide Promotes Cell Survival and Differentiation as Kinase Inhibitor in Human Pluripotent Stem Cells. Stem Cell Reports. 2018, 11(6):1347-1356.
  5. Mulero, M.C., Shahabi, S., Ko, M.S., Schiffer, J.M., Huang, D-B., Wang, V.Y.,Amaro, R.E., Huxford, T., Ghosh, G. Protein Cofactors Are Essential for High-Affinity DNA Binding by the Nuclear Factor κB RelA Subunit. Biochemistry2018, 57(20):2943-2957. DOI:10.1021/acs.biochem.8b00158.
  6. Mulero, M.C., Huang, D-B., Nguyen, H.T., Wang, V.Y.,Li, Y., Biswas, T., Ghosh, G. DNA-binding affinity and transcriptional activity of the RelA homodimer of nuclear factor κB are not correlated. J Mol Biol. 2017, 292(46):18821-18830. DOI:10.1074/jbc.M117.813980.
  7. Wang, V.Y., Li Y., Kim, D., Zhong, X.Y., Ghassemian, M., and Ghosh, G. Bcl3 Phosphorylation by Akt, Erk2 and IKK1 is Required for Its Activation. Mol Cell2017, 67(1), 1-14. DOI: https://doi.org/10.1016/j.molcel.2017.06.011.
  8. Fusco, A.J., Mazumder, A., Wang, V.Y.,Tao, Z., Ware, C., and Ghosh, G. The NF-κB subunit RelB controls p100 processing by competing with the kinases NIK and IKK1 for binding to p100. Sci Signal2016, 9(447):ra96. DOI: 10.1126/scisignal.aad9413.
  9. Sansó, M., Levin, RS., Lipp JJ, Wang, V.Y., Greifenberg, AK., Quezada, EM., Ali, A., Ghosh, A., Larochelle, S., Rana, TM., Geyer, M., Tong, L., Shokat, KM., Fisher, RP. P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates. Genes Dev.2016, 30(1), 117-131.
  10. Wang, V.Y., Jiao, X., Kiledjian, M., and Tong, L. Structural and biochemical studies of the distinct activity profiles of Rai1 enzymes. Nucleic Acids Res2015, 43(13), 6596-6606.
  11. Wang, V.Y.,Huang, W., Asagiri, M., Spann, N., Hoffmann, A., Glass, C., and Ghosh, G. The transcriptional specificity of NF-kB Dimers is coded within the kB DNA Response elements. Cell Rep. 2012, 2(4), 824-839.
  12. Ghosh, G., Wang, V.Y.,Huang, D-B., and Fusco, A.J. NF-kB Regulation: Lessons from Structures. Immunological Rev2012, 246, 36-58.
  13. Fusco, A.J., Huang, D-B., Miller, D., Wang, V.Y.,Vu, D., and Ghosh, G. NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes. EMBO Rep2009, 10, 152-159.
  14. Moorthy, A.K., Huang, D-B., Wang, V.Y.,Vu, D., and Ghosh, G. X-ray structure of a NFkappaB p50/RelB/DNA complex reveals assembly of multiple dimers on tandem kappaB sites. J Mol Biol. 2007, 373, 723-734.
  15. Moorthy, A.K., Savinova, O.V., Ho, J.Q., Wang, V.Y., Vu, D., and Ghosh, G. The 20S proteasome processes NF-kappaB1 p105 into p50 in a translation-independent manner. EMBO J2006, 25, 1945-1956.
Research Grants
PI, Macau Giant Panda Fund: “Giant Panda Dental Clinical Application and Research Project”
09/2019 – 09/2022 PI, Mechanistic Study of NFkappaB and Oncoprotein Bcl3 in Transcriptional Regulation (FDCT 0104/2019/A2)
PI, FDCT 0025/2019/PS
01/2019 – 12/2021 PI, Investigation of IκB:NF-κB:DNA Ternary Complex (MYRG2018-00093-FHS)
Co-PI, MYRG2018-00091-ICMS
PI, FDCT 025/2017/P
02/2017 – 02/2019 PI, Investigation of how the NF-κB signaling family binding to κB modules correlates with target gene transcriptional activity (SRG2016-00084-FHS)
02/2016 – 07/2019 PI, Structural and Functional Studies of Transcription Factor NF-kB Subunit p52 and Oncoprotein Bcl3 (FDCT 023/2016/A1)