Current Research

Our research interests focus on the combination of analytical technologies (mass spectrometry, liquid chromatography, and ion mobility) with biological chemistry in order to address problems in protein and carbohydrate structure and function.  The majority of our projects revolve around the analysis of protein-reactive oxygen species products.  We develop and apply methods that utilize reactive oxygen species (most notably hydroxyl radicals) to label the surfaces of proteins, protein-protein complexes, and protein-carbohydrate complexes.  Changes in surface labeling as measured by mass spectrometry reflect changes in the accessibility of different parts of the protein.  We have used this technology to determine the protein-protein and protein-carbohydrate interaction interfaces, as well as to develop models for the oligomerization process of large chemokine multimers.  We also study the chemistry and structural consequences of protein-reactive oxygen species reactions in conditions of oxidative stress, both as pathological events in human cells and as defense mechanisms in the immune response against invading pathogens.  For example, we are developing methods for identifying and characterizing proteins in H. pylori (the bacterium that causes most peptic ulcers) that are damaged by reactive oxygen species during the host's immune response, as well as characterizing the repair of these proteins by the bacterium's innate repair mechanisms.  Other projects include the development of methods to characterize the structure of sulfated glycosaminoglycan oligosaccharides within complex mixtures, a task that is made more difficult by the fragile nature of the sulfation modification and the presence of a large number of isomeric forms of the sugar that differ only by the site(s) of sulfation.  Major analytical instrumentation located within our group include a hybrid linear ion trap-FTICR mass spectrometer, a quadrupole-travelling wave ion mobility-time of flight mass spectrometer, and HPLC and nanoUPLC systems.  These tools, along with strong collaborations with other groups both at UGA and in the larger research community, allow us to address some of the more difficult problems in bioanalytical chemistry through integration of biological chemistry and multiple analytical platforms.

Selected Publications

Mahawar, M. ; Tran, V. ; Sharp, J. S. ; Maier, R. J. Synergistic Roles of Helicobacter pylori Methionine Sulfoxide Reductase and GroEL in Repairing Oxidant-damaged Catalase. Journal of Biological Chemistry 2011, 286, 19159-19169.
Pomin, V. H. ; Sharp, J. S. ; Li, X. Y. ; Wang, L. C. ; Prestegard, J. H. Characterization of Glycosaminoglycans by (15)N NMR Spectroscopy and in Vivo Isotopic Labeling. Analytical Chemistry 2010, 82, 4078-4088.
Bern, M. ; Saladino, J. ; Sharp, J. S. Conversion of methionine into homocysteic acid in heavily oxidized proteomics samples. Rapid Communications in Mass Spectrometry 2010, 24, 768-772.
Saladino, J. ; Liu, M. ; Live, D. ; Sharp, J. S. Aliphatic Peptidyl Hydroperoxides as a Source of Secondary Oxidation in Hydroxyl Radical Protein Footprinting. Journal of the American Society for Mass Spectrometry 2009, 20, 1123-1126.
Gau, B. C. ; Sharp, J. S. ; Rempel, D. L. ; Gross, M. L. Fast Photochemical Oxidation of Protein Footprints Faster than Protein Unfolding. Analytical Chemistry 2009, 81, 6563-6571.
Watson, C. ; Janik, I. ; Zhuang, T. ; Charvatova, O. ; Woods, R. J. ; Sharp, J. S. Pulsed Electron Beam Water Radiolysis for Submicrosecond Hydroxyl Radical Protein Footprinting. Analytical Chemistry 2009, 81, 2496-2505.
Charvátová, O. ; Foley, B. L. ; Bern, M. W. ; Sharp, J. S. ; Orlando, R. ; Woods, R. J. Quantifying Protein Interface Footprinting by Hydroxyl Radical Oxidation and Molecular Dynamics Simulation: Application to Galectin-1. Journal of the American Society for Mass Spectrometry 2008, 19, 1692-1705.