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B.A. in Chemistry, 1960, St. Olaf College; M.S. in Biochemistry, 1963, University of Wisconsin; Ph.D. in Biochemistry, 1967, University of Wisconsin; Postdoctoral Fellow, 1967-1969, University of Minnesota.
Research
interests: aging and protein
damage from oxidative and nitrosative stress, protein antioxidant systems for reactive
species such as nitric oxide and oxygen radicals, cultured cells as models for
oxidative and nitrosative effects on proteins.
Dr. Thomas's research centers on
the vital role of reactive sulfhydryls (SH groups) as antioxidants and as sites
of irreversible protein damage in cultured cells and intact animals. Reactive
sulfhydryls are found on proteins located in all cellular compartments, and
they are also present on such low molecular weight materials such as
glutathione, cysteine, homocysteine, and coenzyme A. Sulfhydryls are vital to
cell survival, during stress produced by chemical toxicity, in reoxygenation of
transplanted or diseased tissues, and in radiation damage. It is now clear that
they are a vital link to understanding such diverse human diseases as HIV
infection, amyotrophic lateral sclerosis (Lou Gerhrig's disease), and aging.
Dr. Thomas's research has pioneered the study of protein
S-thiolation/dethiolation (reversible formation of disulfide adducts between
protein sulfhydryls and the sulfhydryl of glutathione). Information has been
obtained by modeling the process with pure proteins and studying its function
in intact cells. The crystal structure of the S-thiolated form of carbonic
anhydrase III has been determined. Work on the reductive reactions in cells
(dethiolation) showed that glutaredoxin is and essential part of this process.
Recent experiments have been targeted at understanding nitrosative stress and
protein S-nitrosylation as a component of protein sulfhydryl metabolism. In addition,
study of irreversible damage to protein sulfhydryls has 
produced
interesting results.
Current research
projects include (1) the role of oxygen radicals and nitric oxide in the
S-thiolation and S-nitrosylation of signal transduction proteins (as shown on
the right), and (2) the potential irreversible damage to protein sulfhydryls
that might occur during disease and/or aging when glutathione protection is
inadequate. Several new methods have been developed to study the irreversible
damage that accumulates in specific proteins such as carbonic anhydrase III,
creatine kinase, H-ras, and p53.
Selected Publications
Sun, X.Z., et al. (2003) Formation of disulfide bond in p53 correlates
with inhibition of DNA binding and tetramerization. Antioxid. Redox Signal.
5, 655-665.
Mallis, RJ., Hamann, MJ., Zhao, W., Zhang, T, Hendrich, S., and Thomas, JA . “Irreversible Thiol oxidation in Carbonic Anhydrase III: Protection by S-glutathiolation and Detection in Aging Rats.”, Biol.Chem., 383, 649-662 (2002) link
Thomas, J.A., and Mallis, R.J., "Aging and oxidation of Reactive Protein Sulfhydryls." Expt. Gerontology, 36, 1519-26 (2001). link
Hamann, M., Zhang, T., Hendrich, S., and Thomas, J.A., "A Method for Quantitation of Protein Sulfinic and Sulfonic Acid, Irreversibly Oxidized Protein Cysteine Sites in Cellular Proteins." In Methods in Enzymology, "Protein Sensors of Reactive Oxygen Species: Selenoproteins, Thioredoxin, Thiol Enzymes and Proteins." Ed. Lester Packer and Helmut Sies, Academic Press, Inc., Orlando FL., 348, 146-156 (2002). link
Thomas, J.A., Mallis, R., and Sies, H., "Protein S-thiolation, S-Nitrosylation, and Irreversible Sulfhydryl Oxidation: Roles in Redox Regulation." In Cellular Implications of Redox Signaling , Ed. Carlos Gitler and Avihai Danon, Imperial College Press, London. (August, 2003). pp141-174.
Mallis, R.J., Buss, J.E., and Thomas, J.A., "Oxidative modification of H-RAS; S-thiolation and S-nitrosylation of reactive cysteines." Biochem. J. , 355, 145-153 (2001). link
Mallis, R.J., and Thomas, J.A., "Effect of S-Nitrosothiols on Cellular Glutathione and Reactive Protein Sulfhydryls." Arch. Biochem. Biophys., 383 , 60-69 (2000). link
Mallis, R.J., Poland, B.W., Chatterjee, T.K., Fisher, R.A., Darmawan, S., Honzatko, R.B., and Thomas, J.A., "Crystal Structure of S-Glutathiolated Carbonic Anhydrase III." FEBS Letters,482, 237-241 (2000). link
Wu, H.H., Thomas, J.A., and Momand, J., "p53 Protein Oxidation in Cultured Cells in Response to PDTC – A Novel Method for Relating the amount of p53 Oxidation in vivo to the Regulation of p53-responsive Genes." Biochem. J., 351, 87-93 (2000). link
Ji, Y., Akerboom, T. P. M., Sies, H., and Thomas, J.A., "S-Nitrosylation and S-Glutathiolation of Protein Sulfhydryls by S-Nitroso Glutathione." Arch. Biochem. Biophys. 362, 67-78 (1999) link
Y. Ji, T.P.M. Akerboom, H. Sies and J.A. Thomas, "Gel electrofocusing method for studying protein S-nitrosylation," in Methods in Enzymology, "Protein S-Nitrosylation," ed. Lester Packer, Academic Press, Inc., Orlando FL., 301, 145-151 (1999).
J.A. Thomas, "Oxidative stress, oxidant defense, and dietary constituents." In M.E. Shils, J.A. Olson, M. Shike, and A. C. Ross, eds., Modern Nutrition in Health and Disease, ninth edition, Lea and Febiger, Philadelphia, PA pp. 751-760 (1999).
cDNA sequence of rat liver carbonic anhydrase III, R.J. Mallis, C-H. Jung, T.K. Chatterjee, R.A. Fisher and J.A. Thomas, GenBank Accession no. AF037072. (1998)
J.N. Caamano, Z.Y. Ryoo, J.A. Thomas and C.R. Youngs, "B-MercaptoEthanol enhances blastocyst formation rate and cell number of bovine IVM/IVF embryos." Biol. Reproduction 55(5), 1179-1184 (1996).
C-H. Jung and J.A. Thomas, "S-glutathiolated hepatocyte proteins and insulin disulfides as substrates for reduction by glutaredoxin, thioredoxin, protein disulfide isomerase, and glutathione." Arch Biochem. Biophys.335, 61-72 (1996).
T. Seres, V. Ravichandran, T. Moreguchi, R. Kazuhito, J.A. Thomas and R.B. Johnston, Jr. "Protein S-thiolation and dethiolation during the respiratory burst in human monocytes: A reversible post-translational modification with potential for buffering the effects of oxidant stress." J. Immunol, 156, 1973-1980 (1996).
J.A. Thomas, B. Poland and R. Honzatko, "Perspectives: Protein sulfhydryls and their role in the antioxidant function of protein S-thiolation." Arch. Biochem. Biophys. 319, 1-9 (1995). link
J.A. Thomas, W. Zhao, S. Hendrich and P. Haddock, "Analysis of cells and tissues for S-thiolation of specific proteins" in Methods in Enzymology, "Biothiols," ed. Lester Packer, Academic Press, Inc., Orlando FL. 251 , 423-429 (1995).
J.A. Thomas, Y-C. Chai and C-H. Jung, "Protein S-thiolation and dethiolation" in Methods in Enzymology, "Oxygen Radicals in Biological Systems," Part C., ed. Lester Packer, Academic Press, Inc., Orlando FL., 233, 385-395 (1994).
Y-C. Chai, S.S. Ashraf, K. Rokutan, R.B. Johnston, Jr., and J.A. Thomas , "S-thiolation of individual human neutrophil proteins including actin by stimulation of the respiratory burst: Evidence against a role for glutathione disulfide." Arch. Biochem. Biophys. 310 264-272 (1994).
Y-C. Chai, S. Hendrich and J.A. Thomas, "Protein S-thiolation in hepatocytes stimulated by t-Butyl hydroperoxide, menadione, and neutrophils." Arch. Biochem. Biophys. 310, 273-281 (1994).
V. Ravichandran, R. Seres, T. Moriguchi, J.A. Thomas and R.B. Johnston, Jr., "S-thiolation of glyceraldehyde 3-phosphate dehydrogenase induced by the phagocytosis-associated respiratory burst in blood monocytes." J. Biol. Chem. 269, 25010-15015 (1994).
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