Radical-Induced Protein Oxidation Using Biological Mass Spectrometry:
From Fundamental Studies, Instrumentation and Bioanalytical to Biomedical Applications
Our cross-disciplinary group is actively engaged in the fundamental, instrumental, and applied aspects of biological MS. We perform MS experiments and employ computational models to study the fundamental mechanisms, energetics, and kinetics of peptide radical ion formation and dissociation. Understanding the fragmentation of peptide radical ions forms the scientific basis underlying the establishment of gas phase peptide sequencing strategies, which are central to the emerging field of MS-based proteomics. Interdisciplinary research in our group focuses on the development of new instrumentation and techniques in liquid chromatography (LC)/MS for the analysis and characterization of biomolecules, metabolites, and their posttranslationally modified (PTM) products; it stems from the fundamental research and development of instrumentation. We have developed sensitive, efficient, and automated multidimensional LC/MS methodologies and tools for both qualitative and quantitative proteomics, glycomics, and metabolomics analyses of complex biological samples in order to unravel radical-induced biochemical mechanisms under oxidative stress of a large number of pathophysiological conditions, ranging from neurodegenerative disorders, stroke, and aging to pathogen–macrophage invasion processes. For more information, please visit
Biophysicals and Fundamental
Radicals of biomolecules are believed to play important roles in a variety of biological processes, including aging and Parkinson’s disease, but their biochemical mechanisms are understood quite poorly at the molecular level. Dissociations of radical peptides and proteins can occur through several important chemical processes, including fragmentation, isomerization, and electron, hydrogen atom, and proton transfer. Combinations of MS experiments and computational models have been used to examine the fundamental mechanisms, energetics, and kinetics of peptide radical ion chemistry.
Bioanalyticals and Next Generation
Mass Spectrometry Instrumentation:
We are actively
engaged in the development of new instrumentation and techniques for
the bioanalytical applications of liquid chromatography/mass
spectrometry. In collaboration with MDS-SCIEX and IONICS (Canada), we modify existing
mass spectrometric hardware to explore new avenues for proteomic,
glycomic, and metabolomic analyses. Our goals are to develop
sensitive, efficient, and novel mass spectrometric methodologies.
Biomedical Applications :
We are applying multidimensional LC/MS platforms, designed in-house, to the characterization of global and redox proteomic changes, with a particular emphasis on RNS-mediated modification of proteins, particularly 3-nitrotyrosine–containing proteins—a selective and irreversible PTM biomarker for radical-mediated protein oxidation and a hallmark of various diseases—and triggered downstream signaling pathways involving tyrosine phosphorylation. The biological conditions currently under investigation include stroke, neurodegenerative disorders, and pathogen–macrophage invasion processes.
analysis of endothelial cells
B: A novel metabolic
gene in sorghum and zebrafish embryos;
C: MRI image of DDD
(Degenerative Disc Disease);
D: MRI image of Macaca
brain (Degenerative disorder)
1. Zhao Y, Szeto SSW, Kong PW, Law CH, Li G, Quan Q, Zhang Z, Chu IK. Anal. Chem. 2014, in press.
2. Law CH, Kong PW, Szeto SSW, Li G, Quan Q, Zhang Z, Chu IK. Analyst. 2014, in press.
3. Quan Q, Song T, Hao Q, Siu CK, Chu IK. J. Am. Soc. Mass Spectrom. 2013, 24 (4), 554-562.
4. Kong PW, Hao Q, Lai CK, Siu CK, Chu IK, J. Am. Soc. Mass Spectrom. 2012, 23 (12), 2094-2101.
5. Song, T.; Hao, Q.; Law, C. H.; Siu, C. K.; Chu IK. J. Am. Soc. Mass Spectrom. 2012, 23 (2), 264-273.
6. Kong PW, Siu SO, Lee SMY, Lo C, Chu IK. J. Chromatogr. A 2011, 1218(23), 3681-3688.
7. Siu SO, Lam MPY, Lau E, Kong PW, Zhang J, Lee SMY, Chu IK. Proteomics. 2011, 11(11), 2308-2319.
8. Laskin J, Yang ZB, Song T, Lam CNW, Chu IK. J. Am, Chem. Soc. 2010, 132(45), 16006-16016.
9. Laskin J, Yang Z, Chu IK. J. Am. Chem. Soc. 2008, 130, 3218-3230.
10. Chu IK, Zhao J, Xu M, Siu SO, Hopkinson AC, Siu KWM. J. Am. Chem. Soc. 2008, 130, 7862-7872.
11. Laskin J, Futrell JH, Chu IK. J. Am. Chem. Soc. 2007, 129, 9598-9599.
12. Laskin J, Yang ZB, Lam C, Chu IK. Anal. Chem. 2007, 79, 6607-6614.
Invited book chapter and review article:
1. Lam MPY, Law CH, Quan Q, Zhao Y, Chu IK, Shotgun Proteomics: Methods and Protocols, Methods in Molecular Biology, 2014, vol.1156, 39-51
2. Chu IK, Laskin J, Formation of peptide radical ions through dissociative electron transfer in ternary metal-ligand-peptide complex. Eur. J. Mass Spectrom. 2011, 17 (6), 543-556.