Dr. Hui Zhang
Assistant Professor, Pathology
Protein modification is one of the key mechanisms that governs the diverse protein structure and function, and plays a significant role in the development of many diseases such as cancer. Unfortunately, the dynamic nature of protein modification remains uncharacterized, which is one of the major bottlenecks to biochemical research.
My primary research goal is to study protein modification on the proteome scale and the effects of modification on protein function and disease progression. For the past few years, my research has been focused on developing high-throughput technologies to isolate and identify two of the most abundant protein modifications - phosphorylation and glycosylation. One technology enables capturing and identification of modified peptides using affinity chromatography. To do so, I have developed a group of antibodies reactive against a variety of protein modification sites, such as phosphorylation, nitration, acetylation, and substrates of a specific modification enzyme, etc. Among those, phospho-specific antibodies have enabled isolation of a large number of phosphorylated peptides that can be subsequently identified by tandem mass spectrometry. The second technology enables capturing glycopeptides using solid phase extraction, which has become a powerful tool to analyze glycoproteins on cell surface and in body fluids. Thus far, thousands of novel glycosylation sites have been identified from different tissues using this novel glycopeptide capture technology; this significantly expends the limited number of experimentally identified glycosylation sites prior to the new technology. These methods are highly sensitive, holding a strong promise for discovering low abundance disease marker proteins in tissue, plasma or other body fluids.
Currently, we are applying these proteomics technologies to determine protein modifications associated with cancer for early detection and monitoring therapeutic effects as well as developing novel methods to study protein modifications that will have major implications for human health.
Tian, Y., Zhou, Y., Elliott, S., Aebersold, R., and Zhang. H. Solid-phase extraction of N-linked glycopeptides. Nature Protocols (2007) 2: 334.
Zhang, H., Liu, A. Y., Loriaux, P., Wollscheid, B., Zhou, Y., Watts, J. D., and Aebersold, R. Mass spectrometric detection of tissue-derived proteins in blood. Molecular & Cellular Proteomics (2007) 6: 64.
Zhang, H., Loriaux, P., Eng, J., Campbell, D., Keller, A., Moss, P., Bonneau, R., Zhang, N., Zhou, Y., Wollscheid, B., Cooke, K., Yi, E. C, Lee, H, Peskind, E. R., Zhang, J., Smith, R. D., and Aebersold, R. UniPep, a database for human N-linked glycosites: A Resource for Biomarker Discovery. Genome Biology (2006) 7: R73.
Zhang, H., Li, X. J., Martin, D. B., and Aebersold, R. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature Biotechnology (2003) 21:660.
Zhang, H., Zha, X., Tan, Y., Hornbeck, P. V., Mastrangelo, A. J., Alessi, D. R., Polakiewicz, R. D., and Comb, M. J. Phosphoprotein analysis using antibodies broadly reactive against phosphorylated motifs. Journal of Biological Chemistry (2002) 277:39379.