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Christian Schöneich Ph.D.
Professor and Chair
Departments: Pharmaceutical Chemistry
Office: 236C Simons
Email: schoneic@ku.edu
Phone: (785) 864-4880
Fax: (785) 864-5736

Educational Background:

Diplom, 1987, Free University Berlin (Germany)
Ph.D., 1990, Technical University Berlin (Germany)

Research Group:

  • Gary Gerstenecker: Graduate Student
  • Giridhan Gokulrangan: Post-Doctoral Researcher
  • Asha Hewarathna: Graduate Student
  • Geetha Hewawasam: Graduate Student
  • Sung Jung Hong: Graduate Student
  • Xiaobao Li: Post-Doctoral Researcher
  • Olivier Mozziconacci: Postdoctoral Researcher
  • Victor Sharov: Research Assistant Professor
  • Maria Thorson: Graduate Student
  • Dremina Yelena: Research Assistant Professor

Research Interests:

Mechanisms of free radical reactions, protein stability, anticancer agents

Professor Schöneich's research focuses on the oxidative post-translational modification of proteins in vitro and in vivo. These are generally carried out by reactive oxygen species and/or reactive nitrogen species. In vivo, such oxidative modifications accompany physiological disorders associated with biological aging or disease. While major scientific advances have been made through the sequencing of the human genome, it has been recognized that in many cases only the detailed characterization and quantification of the protein complement (the "proteome") will lead to an accurate understanding of human disease and aging. Moreover, in addition to quantification of the expression levels of certain proteins a detailed map of their post-translational modifications is necessary. Such research is carried out in our group. We are using state-of-the-art analytical proteomics and tandem mass spectrometry techniques to characterize post-translationally modified proteins in tissue. Experiments involve two-dimensional gel--electrophoresis and two-dimensional HPLC separations, coupled to MALDI-TOF or electrospray ionization mass spectrometry analysis on either Q-TOF2 or ion trap instrumentation. We are currently involved in the building of an interdisciplinary "Proteomics Center" at the University of Kansas, which, by Fall 2004, will be equipped with the newest generations of MALDI-TOF/TOF, MALDI-QqTOF and linear ion trap instruments. For the quantification of distinct post-translational modifications, we are designing specific labeling chemistries, which allow the targeted enrichment of specifically modified peptides from complex biological samples. For example, we have recently characterized specific S-glutathiolated sequences of a membrane protein, the sarco/endoplasmic reticulum Ca-ATPase, as a result of exposure to the biological messenger nitric oxide (NO). An additional focus of our research is to understand the actual mechanisms of oxidation, and the effect of protein structure on these reactions. In vivo, only selected proteins suffer oxidative modifications, which may be the result of chemical selectivity, protein structure, the rates of protein turnover, and/or specific protein-protein interactions.

In vitro, i.e. in pharmaceutical formulations, protein oxidation presents an important stability problem. We are interested to generate a database which relates oxidation sensitivity to specific structural elements of proteins. With such a database at hand, we can potentially predict the stability of new protein products, facilitating pharmaceutical development. To achieve such a database, we are studying oxidative protein stability for proteins in (a) solution, (b) in polymeric matrices, and (c) in the solid state.

Current Research Projects:

 
 

Maria Thorson: Schöneich Lab Group

Proteomics tools (fluorescent tags) for the detection of post-translational protein modifications were developed

The mechanisms of protein oxidation in vivo and in vitro are being examined with this new technology
 
 
 
 

Gary Gerstenecker: Schöneich Lab Group

Differential gel electrophoresis

HPLC-MS/MS analysis

FTICR-Mass spectrometry
 
 

Publications:

S.J. Hong, G. Gokulrangan and Ch. Schöneich, "Proteomic analysis of age-dependent nitration of rat cardiac proteins by solution isoelectric focusing coupled to nano-HPLC tandem mass spectrometry". Exp. Gerontol. 2007, 42, 639-651.

K. Bobrowski, G.L. Hug, D. Pogocki, B. Marciniak and Ch. Schöneich, "Stabilization of sulfide radical cations through complexation with the peptide bond: mechanisms relevant to oxidation of proteins containing multiple methionine residues". J. Phys. Chem. B 2007, 111, 9608-9620.

K. Bobrowski, G.L. Hug, D. Pogocki, B. Marciniak and Ch. Schöneich, "Sulfur radical cation-peptide bond complex in the one-electron oxidation of S-methylglutathione". J. Am. Chem. Soc. 2007, 129, 9236-9245.

G. Gokulrangan, A. Zaidi, M.L. Michaelis, and Ch. Schöneich, "Proteomic analysis of protein nitration in rat cerebellum: effect of biological aging". J. Neurochem. 2007, 100, 1494-1504.

Ch. Schöneich and V.S. Sharov, "Mass spectrometry of protein modifications by reactive oxygen and nitrogen species". Free Radic. Biol. Med. 2006, 41, 1507-1520.

E.S. Dremina, V.S. Sharov and Ch. Schöneich, "Displacement of SERCA from SR caveolae-related domains by anti-apoptotic protein Bcl-2: a possible mechanism for SERCA inactivation". Biochemistry 45, 175-184 (2006).

J. Kanski, S.J. Hong and Ch. Schöneich, "Proteomic analysis of protein nitration in aging skeletal muscle and identification of nitrotyrosine-containing sequences in vivo by nanoelectrospray ionization tandem mass spectrometry". J. Biol. Chem. 280, 24261-24266 (2005).

E.S. Dremina, V.S. Sharov and Ch. Schöneich, "Protein tyrosine nitration in rat brain is associated with raft proteins, flotillin-1 and alpha-tubulin: effect of biological aging. J. Neurochem. 93, 1262-1271 (2005).

T. Adachi, R.M. Weisbrod, D.R. Pimentel, J. Ying, V.S. Sharov, Ch. Schöneich and Cohen, "S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide. A mechanism targeted by oxidants in vascular disease”. Nature Medicine 10, 1200-1207 (2004).

E. Dremina, V. Sharov, K. Kumar, A. Zaidi, E.K. Michaelis and C. Schöneich, "Anti-apoptotic protein Bcl-2 interacts with and destabilizes the sarcoplasmic/endoplasmic reticulum Ca-ATPase", Biochem. J. 383, 361-370(2004).

H.K. Khor, M.T. Fisher and C. Schöneich, "Potential role of methionine sulfoxide in the inactivation of the chaperone GroEL by hypochlorous acid (HOCl) and peroxynitrite (ONOO-)", J. Biol. Chem. 279, 19486-19493 (2004).

J. Kanski, M.A. Alterman and C. Schöneich, "Proteomic identification of age-dependent protein nitration in rat skeletal muscle", Free Radical Biol. Med. 35, 1229-1239 (2003).

C. Schöneich, D. Pogocki, G.L. Hug and K. Bobrowski, "Free radical reactions of methionine in peptides: mechanisms relevant to beta-amyloid oxidation and Alzheimer's disease", J. Am. Chem. Soc. 125, 13700-13713 (2003).

T. Nauser and C. Schöneich, "Thiyl Radicals Abstract Hydrogen Atoms from the (alpha)C-H Bonds in Model Peptides: Absolute Rate Constants and Effect of Amino Acid Structure," J. Am. Chem. Soc., 125: 2042–2043 (2003).

V. S. Sharov, N. A. Galeva, T. V. Knyushko, D. J. Bigelow, T. D. Williams and C. Schöneich, "Two-dimensional separation of the membrane protein sarcoplasmic reticulum Ca-ATPase for high-performance liquid chromatography-tandem mass spectrometry analysis of posttranslational protein modifications," Anal. Biochem., 308: 328–335 (2002).

C. Schöneich, "Redox processes of methionine relevant to beta-amyloid oxidation and Alzheimer's disease," Arch. Biochem. Biophys., 397: 370–376 (2002).

C. Schöneich and T. D. Williams, "Cu(II)-catalyzed oxidation of beta-amyloid peptide targets His13 and His14 over His6: Detection of 2-Oxo-histidine by HPLC-MS/MS," Chem. Res. Toxicol., 15: 717–722 (2002).

D. Pogocki and C. Schöneich, "Redox properties of Met(35) in neurotoxic beta-amyloid peptide. A molecular modeling study," Chem. Res. Toxicol., 15: 408–418 (2002).

S. W. Hovorka, H. Biesiada, T. D. Williams, A. Huhmer and C. Schöneich, "High sensitivity of Zn2+ insulin to metal-catalyzed oxidation: detection of 2-oxo-histidine by tandem mass spectrometry," Pharm. Res., 19: 530–537 (2002).