个人简介

University of Chicago, Illinois, B.S., 1966, Chemistry University of Wisconsin, Madison, Ph.D., 1971, Organic Chemistry (J. A. Berson) Thesis: "Part I: Thermal Unimolecular Carbomethoxyl Migrations; Part II: Approaches to the Study of the Stereochemistry of Vicinal Free Radical Elimination" University of Wisconsin, Madison, Postdoctoral Research Associate, 1970-71, Bioorganic Chemistry (C. J. Sih) Indiana University, Bloomington, Postdoctoral Research Associate, 1971-73, Homogeneous Catalysis (J. K. Kochi)

研究领域

Biochemistry/Chemical Biology/Medicinal Chemistry/Organic Chemistry/Bio-Organic Chemistry/Cellular Biology/Molecular Biology/Natural Products/Pharmacology/Synthesis

The objectives of the group are to understand the role of lipid oxidation in disease, to develop new diagnostic tools for identifying individuals at risk and assessing the efficacy of therapeutic interventions, and to provide a molecular basis for the design of new drugs and strategies for the prevention or treatment of oxidative injury. Dr. Salomon did undergraduate studies at the University of Chicago, graduate and postdoctoral studies at the University of Wisconsin, and further postdoctoral studies at Indiana University. In 1973 he joined the faculty of Case Western Reserve University where he is the Charles Fredrick Mabery Professor of Research in Chemistry. The group's research, built on a foundation of physical and synthetic organic chemistry, bridges chemistry, biology, and medicine. Previous accomplishments and continuing interest focus on the biologically important chemistry of lipids. Discovery of naturally occurring molecules and their biologically important chemistry guided by prior total synthesis of targets identified by mechanistic considerations This unconventional approach was especially effective for the discoveries of levuglandins and isolevuglandins, oxidized lipids that are so extraordinarily reactive that isolating them from biological sources has not been possible. Mechanistic elucidation of lipid oxidative pathways and the reactions of oxidized lipids with biological nucleophiles such as proteins and DNA The reactions of oxidized lipids, such as levuglandins, with proteins and DNA are often toxic events that may contribute to disease processes. Investigation of the influences of biological environments such as membranes and lipoprotein particles, on lipid oxidation and the chemistry of oxidized lipids Compartmentalization and the lipophilic-hydrophilic dichotomy are pervasive characteristics of biological systems. Detection and structural characterization of disease-related lipid-based oxidative modifications of proteins with immunological, mass spectroscopic, and chromatographic tools The exquisite sensitivity and structural selectivity of antibodies are well-suited for detecting posttranslational lipid-based modifications of proteins in biological systems, such as retina. Mass spectroscopic techniques provide an abundance of structural information that allows microscale characterization of the protein targets of lipid-based oxidative modification. Clinical investigation of the involvement of lipid oxidation in disease, such as atherosclerosis Protein adducts of certain lipid oxidation products, e. g., isolevuglandins, provide a dosimeter for oxidative stress that is more closely correlated with cardiovascular disease than are classical risk factors, e. g., total serum cholesterol or LDL cholesterol levels. Protein-bound carboxyethylpyrroles (CEPs) are docosahexaenoate-derived oxidative modifications that are grossly elevated in the retinas of individuals with age-related macular degeneration and in melanoma. Design, synthesis, and evaluation of new medicinal agents Lipophilic histidine-containing nucleophiles that intercept and detoxify electrophilic lipid oxidation products are potentially useful competitive inhibitors of lipid-based oxidative protein modification. Such an antielectrophile defense may complement the well-known antioxidant defenses. Lipophilic analogues are potentially useful inhibitors of receptor-mediated, e.g., CD-36, cellular resopnses to certain oxidized phospholipids.

近期论文

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"Infiltration of proinflammatory M1 macrophages into the outer retina precedes damage in a mouse model of age-related macular degeneration", Cruz-Guilloty, 1. F., Saeed, A. M. Echegaray, J. J., Duffort, S., Ballmick, A., Tan, Y., Betancourt, M., Viteri, E., Ramkhellawan, G. C., Ewald, E., Feuer, W., Huang, D., Wen, R., Hong, L., Wang, H., Laird, J. M., Sene, A., Apte, R. S., Salomon, R. G., Hollyfield, J. G. and Perez, V. L. , Int J Inflam 2013, "Posttranslational modification by an isolevuglandin diminishes activity of the mitochondrial cytochrome P450 27A1" Charvet, C. D., Laird, J., Xu, Y., Salomon, R. G. and Pikuleva, I. A. J Lipid Res 2013, 54, 1421-9. [Abstract] "Engagement of platelet toll-like receptor 9 by novel endogenous ligands promotes platelet hyperreactivity and thrombosis" Panigrahi, 1. S., Ma, Y., Hong, L., Gao, D., West, X. Z., Salomon, R. G., Byzova, T. V. and Podrez, E. A. Circ Res 2013, 112, 103-12. [Abstract] "Metabolomics and mass isotopomer analysis as a strategy for pathway discovery: Pyrrolyl and cyclopentenyl derivatives of the pro-drug of abuse, levulinate" Harris, S. R., Zhang, G., Sadhukhan, S., Wang, H., Shi, C., Puchowicz, M. A., Anderson, V. E., Salomon, R. G., Tochtrop, G. P., Brunengraber, H. Chem Res Toxicol 2013, 26, 213-20. [Abstract] "Structural Identification and Cardiovascular Activities of Oxidized Phospholipids" Salomon, R. G. Circ. Res 2012, 111, 930-946. [Abstract] "NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components"Doyle, S. L., Campbell, M., Ozaki, E., Salomon, R. G., Mori, A., Kenna, P. F., Farrar, G. J., Kiang, A. S., Humphries, M. M., Lavelle, E. C., O'Neill, L. A., Hollyfield, J. G., and Humphries, P. , Nature Med, 2012 [Abstract] "Fragmentation of β-Hydroxy Hydroperoxides" Gu, X.; Zhang, W.; Salomon, R. G.. J Org Chem 2012, 77, 1554-9. [Abstract] "Fragmentation of a Linoleate-derived γ-Hydroperoxy-α,β-unsaturated Epoxide to γ-Hydroxy- and γ-Oxo-alkenals Involves a Unique Pseudo Symmetrical Diepoxycarbinyl Radical" Gu, X., Salomon, R.G., Free Rad Biol Med, 2012, 52, 601-6. [Abstract] "Discovery of Carboxyethylpyrroles (CEPs): Critical Insights into AMD, Autism, Cancer, and Wound Healing from Basic Research on the Chemistry of Oxidized Phospholipids" Salomon, R. G.; Hong, L.; Hollyfield, J. G., Chem Res Toxicol 2011, 24, 1803-16. [Abstract] "Critical Insights into Cardiovascular Disease from Basic Research on the Oxidation of Phospholipids: The g-Hydroxyalkenal Phospholipid Hypothesis" Salomon, R. G.; Gu, X., Chem Res Toxicol 2011, 24, 1791-802. [Abstract] "Isolevuglandins and mitochondrial enzymes in the retina: mass spectrometry detection of post-translational modification of Sterol-metabolizing CYP27A1" Charvet, C., Liao, W. L., Heo, G. Y., Laird, J., Salomon, R. G., Turko, I. V. and Pikuleva, I. A. J Biol Chem 2011, 286, 20413–22. [Abstract] "An 1O2 Route to γ-Hydroxyalkenal Phospholipids by Vitamin E Induced Fragmentation of Hydroperoxydiene-derived Endoperoxides" Gu, X., Choi, J., Li, W., Chen, X., Laird, J., and Salomon, R.G. Chem Res Toxicol. 2011, 24,1080-93. [Abstract] "Lysophosphatidylcholine is Generated by Spontaneous Deacylation of Oxidized Phospholipids" Choi, J., Zhang, W., Gu, X., Chen, X., Hong, L., Laird, J. M. and Salomon, R. G. Chem Res Toxicol. 2011, 24, 111-8. [Abstract] "An efficient synthesis of γ-hydroxy-a,ß-unsaturated aldehydic esters of 2-lysophosphatidylcholine" Choi, J., Laird, J. M. and Salomon, R. G. Bioorg Med Chem. 2011, 19, 580-587. [Abstract]