A holistic view and understanding of a complex biological system demands comprehensive qualitative and quantitative information of proteins, the products of genes that define cellular functions. Unfortunately, traditional biochemical methods do not easily deliver such information with high speed, superior resolution, and sufficient accuracy, creating a major bottleneck for the biomedical research discovery process. My laboratory is interested in developing mass spectrometry-based proteomics technologies to address this challenge. Our approach is targeted studies of functional sub-proteomes using integrated, novel technologies involving biochemistry, protein chemistry, synthetic organic chemistry, and mass spectrometry-based proteomics methods. Our methods offer advantages compared with traditional proteomics approaches with higher sensitivity and wider dynamic range. Ultimate goal of our technology development research is to provide powerful methods that allow to efficiently generate information for high-resolution molecular description and characterization of a complex cellular system.
Technology development
New technologies are the ultimate source from which innovative biology springs. A novel, powerful method enables the researcher to efficiently carry out studies in systems not amenable to conventional techniques. Thus, development of novel methods is of paramount importance for biology to evolute and access to these technologies is essential to scientists who seek to be at the forefront of their fields. For this reason, we are developing cutting-edge functional proteomics technologies in the following areas:
1. Sensitive mass spectrometry methods for protein identification, quantification, and mapping modification sites; 2. Novel proteomics technologies for detection, isolation, and quantification of post-translational modifications, including phosphorylation, lipid modification, and glycosylation; 3. Isolation and quantification of integral plasma membrane proteins; 4. Dissection of protein-protein interactions for elucidating signal transduction pathways and network regulations.
Biological applications of proteomics technologies
We use these powerful proteomics technologies in conjunction with biochemistry to study systems biology that have major implications for human health and are not amenable to conventional methods. Representative research projects are:
1.Identification of overexpressed cancer-cell surface proteins for anti-tumor drug design; 2.Construction of blueprints for protein phosphorylation and lipid modifications; 3.Characterization of signal transduction pathways and network regulations by dissection of protein-protein interactions. 4.Molecular characterization of O-GlcNAc modifications and its role in diabetics; 5.Identification of down-stream protein targets for farnesyltransferase inhibitors currently under clinical trials.
RESEARCH INTERESTS
Functional Proteomics
Biological Mass Spectrometry
Phosphoproteomics
Systems biology
RECENT PUBLICATIONS
Kwon, S. W., Kim, S. C., Jaunbergs, J., Falck, J. R. & Zhao, Y., "Selective-enrichment of thiophosphorylated polypeptides as a tool for the analysis of protein phosphorylation." Molecular and Cellular Proteomics, 2:242-247, 2003
Zhao, Y., Zhang, W., Kho, Y., and Zhao, Y., "Efficient proteomics analysis of integral plasma membrane proteins," Analytical Chemistry, 76:1817-1823, 2004
Zhao, Y., Kwon, S. W., Anselmo, A., Kau, K., and White, M. A., "Broad-spectrum identification of cellular SUMO substrate proteins" J Biol Chem, 279:20999-21002., 2004
Kho, Y., Deb, B., Jiang, C., Kim, S. C., Cheng, J., Kwon, S. W., Tamanoi, F., Falck, J., and Zhao, Y, "Tagging-via-Substrate (TAS) technology for detection and proteomics analysis of farnesylated proteins" Proc Natl Acad Sci U S A, In press 2004
SIGNIFICANT PUBLICATIONS
Kwon, S. W., Kim, S. C., Jaunbergs, J., Falck, J. R. & Zhao, Y., "Selective-enrichment of thiophosphorylated polypeptides as a tool for the analysis of protein phosphorylation" Molecular and Cellular Proteomics, 2:242-247, 2003
Zhao, Y., Zhang, W., Kho, Y., and Zhao, Y., "Efficient proteomics analysis of integral plasma membrane proteins" Analytical Chemistry, 76:1817-1823, 2004
Zhao, Y., Kwon, S. W., Anselmo, A., Kau, K., and White, M. A., "Broad-spectrum identification of cellular SUMO substrate proteins" J Biol Chem, 279:20999-21002, 2004
Kho, Y., Deb, B., Jiang, C., Kim, S. C., Cheng, J., Kwon, S. W., Tamanoi, F., Falck, J., and Zhao, Y., "Tagging-via-Substrate (TAS) technology for detection and proteomics analysis of farnesylated proteins" Proc Natl Acad Sci U S A, In press 2004
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