K.W. Michael Siu
PhD (Dalhousie University)
Research Areas: Proteomics and Mass Spectrometry
We are developing novel proteomics technologies and methodologies for rapid and comprehensive protein identification and sequencing. These are applied to chart the proteomes of selected organisms or specific tissues.
Mass Spectrometry. Modern mass spectrometry (MS) is the main tool used in proteomics. Research in mass spectrometry includes fundamental studies aimed at studying how protein and peptide ions are formed in the gas phase, examination of structures and energetics of these ions, developing new sequencing methodologies, and applying mass spectrometric techniques for rapid protein identification and characterization.
Separation Technologies. The proteome is a complex mixture of proteins. A prerequisite to mass spectrometric analysis of the proteome is high-resolution separation. Both comprehensive and selective separation strategies are under development. Selective methodologies are typically designed for isolating and concentrating low-abundance proteins that are often excluded or swarmed in comprehensive methods. Many low-abundance proteins play crucial roles in signal transduction, regulation and disease initiation.
Applications. Proteomics tools are being applied to identify protein markers in endometrial cancer; this is a project in collaboration with Dr. Terence J. Colgan, Mount Sinai Hospital, and Dr. Alexander D. Romaschin, Toronto General Hospital. The proteomes in the cilia and the nucleus of Tetrahymena thermophila are being examined in collaboration with Professor Ronald E. Pearlman; this has so far proven to be difficult as the Tetrahymena genome is unknown. Phosphorylation sites on myocyte enhancer factor proteins are being mapped in collaboration with Professor John C. McDermott. This has led to methodologies that increase sequencing coverage in MS analysis and selective enhancement of phosphopeptide recoveries in separation.
Selected Publications: Please visit www.chem.yorku.ca/profs/siu/ for a comprehensive listing and the complete papers in PDF format.
Structures of b and a Product Ions from the Fragmentation of Argentinated Peptides.
V. W.-M. Lee, H. Li, T.-C. Lau and K.W.M. Siu, J. Am. Chem. Soc., 120, 7302-7309 (1998).
Sequencing of Argentinated Peptides by means of Electrospray Tandem Mass Spectrometry.
I.K. Chu, X. Guo, T.-C. Lau and K.W.M. Siu, Anal. Chem., 71, 2364-2372 (1999).
Proton Migration and Tautomerism in Protonated Triglycine.
C.F. Rodriquez, A. Cunje, T. Shoeib, I.K. Chu, A.C. Hopkinson and K.W.M. Siu, J. Am. Chem. Soc., 123, 3006-3012 (2001).
Collision-Induced Dissociation of the Ag+-Proline Complex: Fragmentation Pathways and Reaction Mechanisms - A Synergy between Experiment and Theory.
T. Shoeib, A.C. Hopkinson and K.W.M. Siu, J. Phys. Chem. B, 105, 12399-12409 (2001).
Sequencing of Argentinated Peptides by means of Matrix-Assisted Laser Desorption/Ionization (MALDI) Tandem Mass Spectrometry.
I.K. Chu, D.M. Cox, X. Guo, I. Kireeva, T.-C. Lau, J.C. McDermott and K.W.M. Siu, Anal. Chem., published on the WWW, April 6, 2002.