Faculty

Our research focuses on applying state-of-the-art mass spectrometric techniques to the following areas: 1) identification and characterization of protein posttranslational modifications; 2) mapping macromolecular contact surfaces; and 3) exploration of the gas-phase fragmentation behavior of various biomolecules following ion-electron interactions. A major goal is to excel in both analytical technique development and biologically relevant problem solving.

Electron Capture dissociation (ECD) is a recently developed fragmentation technique for gas-phase peptide and protein ions. ECD can cleave backbone bonds with retention of weakly-bound posttranslational modifications, thereby allowing their localization while simultaneously resulting in amino acid sequence information. By contrast, the main dissociation pathways in slow-heating techniques, such as infrared multiphoton dissociation (IRMPD), are loss of and cleavage within modifications. IRMPD can therefore identify the presence of modifications, and provide complementary structural information. We incorporate ECD and IRMPD into the field of proteomics to specifically target modified proteins at low (fmol) levels.

Solution-phase hydrogen/deuterium exchange in combination with mass spectrometric detection of proteolytic peptides is a valuable tool for characterization of protein-protein interactions. The exchange rates of amide hydrogens at contact surfaces generally slow down several orders of magnitude compared to hydrogens accessible to the solvent. We utilize the ultrahigh resolution (m/Delta mFWHM of several million) and ppm mass accuracy of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to improve peptide assignment, protein sequence coverage, and mass increase measurements. We also apply this technology to characterize protein-nucleic acid and protein-carbohydrate interactions, and explore the possibility of employing ECD to increase structural resolution.

Finally, we are interested in extending the radical ion chemistry of ECD and other techniques based on ion-electron interactions to structural characterization of a larger variety of biological molecules, such as oligonucleotides and oligosaccharides. Fragmentation patterns of both positive and negative ions are investigated, and should provide insights for a deeper understanding of these processes.

Awards

National Science Foundation Career Award, 2005
Eli Lilly Analytical Chemistry Award, 2005
American Society for Mass Spectrometry Research Award, 2005
Elisabeth Caroline Crosby Research Award, University of Michigan, 2004
Searle Scholar Award, 2004
Swedish Foundation for International Cooperation in Research and Higher Education (STINT) Postdoctoral Fellow

Representative Publications

1. Kweon, H.K. and Hakansson, K., "Selective Zirconium Dioxide-Based Enrichment of Phosphorylated Peptides for Mass Spectrometric Analysis", Anal. Chem., 2006, 78, 1743.

2. Adamson, J.T. and Hakansson, K., "Infrared Multiphoton Dissociation and Electron Capture Dissociation of High Mannose-Type Glycopeptides", J. Proteome Res., 2006, 5, 493.

3. Kweon, H.K. and Hakansson, K., "Site-Specific Amide Hydrogen Exchange in Melittin Probed by Electron Capture Dissociation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry", Analyst, 2006, 131, 275.

4. Yang, J., Mo, J., Adamson, J.T. and Hakansson, K., "Characterization of Oligodeoxynucleotides by Electron Detachment Dissociation Fourier Transform Ion Cyclotron Resonance Mass Spectrometry", Anal. Chem., 2005, 77, 1876.

5. Schultz, K.N. and Hakansson, K., "Rapid Electron Capture Dissociation of Mass-Selectivity Accumnulated Oligonucleotide Dications", Int. J. Mass Spectrom., 2004, 234, 123.