研究领域

Analytical

We employ liquid chromatography-based bioanalytical techniques to probe bioinorganic chemistry-related mechanisms that take place in the mammalian bloodstream. In particular, we pursue three specific research goals. Firstly, we are interested in elucidating toxicologically relevant biotransformations of environmentally abundant toxic metals and metalloid compounds in the bloodstream since these reactions will fundamentally determine the toxic effect at the organ level. Since numerous toxicological studies have demonstrated that toxic metals and metalloid compounds (which are ingested via the diet and drinking water) can adversely affect the metabolism of simultaneously ingested essential elements, we aim to elucidate the underlying molecular mechanisms. To this end, we have structurally characterized two previously unknown metabolites which are formed in the mammalian bloodstream. The fact that these compounds contain As-Se and Hg-Se bonds implies that intestinally absorbed Hg2+ and H3AsO3 (arsenite) will adversely affect the metabolism of selenium. Hence, these metabolites are likely to play a fundamental role in the molecular mechanism underlying the chronic toxicity of Hg2+ and H3AsO3 (in humans. The second major thrust in our group is the application of a recently developed instrumental analytical technique, which is based on the hyphenation of size exclusion chromatography (SEC) with an inductively coupled plasma atomic emission spectrometer (ICP-AES), to directly analyze mammalian plasma for the contained Cu, Fe and Zn-containing metalloproteins. Since it is well known that certain human diseases are associated with increased or decreased plasma concentrations of certain metalloproteins (e.g. Wilson’s Disease patients have a greatly decreased concentration of the plasma Cu-metalloprotein ceruloplasmin), the potential of this technique to diagnose human diseases is currently being investigated. The third research direction focuses on the application of the developed SEC-ICP-AES technique to study the transport of biologically active metal/metalloid-containing compounds (e.g. toxic metals, metalloid compounds) in blood plasma in vitro. This is accomplished by the addition of the compound of interest to plasma and its subsequent analysis by SEC-ICP-AES. Monitoring the emission lines of the element of interest in addition to those of Cu, Fe, and Zn is used to gain insight into the fate of the compound of interest in the bloodstream.

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M. Sooriyaarachchi,* T.T. Morris* and J. Gailer. Advanced LC-analysis of human plasma for metallodrug metabolites. Drug Discov. Today: Technol., 16, 2015, e24-e30. T.T. Morris,* Y. Ruan, V.A. Lewis, A. Narendran and J. Gailer. Fortification of blood plasma from cancer patients with human serum albumin decreases the concentration of cisplatin-derived toxic hydrolysis products in vitro. Metallomis, 6, 2014, 2034-2041. M.A. Garcia-Sevilliano, T. Garcia-Barrea, F. Navarro, J. Gailer, J.L. Gomez-Ariza. Use of elemental and molecular-mass spectrometry to assess the toxicological effects of inorganic mercury in the mouse Mus musculus. Anal. Bioanal. Chem., 406, 2014, 5853-5865. M. Sooriyaarachchi,* J.L. Wedding, H.H. Harris and J. Gailer. Simultaneous observation of the metabolism of cisplatin and NAMI-A in human plasma in vitro by SEC-ICP-AES. J. Biol. Inorg. Chem., 19, 2014, 1049-1053. E.Z. Jahromi,* J. Gailer, I.J. Pickering and G.N. George. Structural characterization of Cd2+ complexes in solution with DMSA and DMPS. J. Inorg. Biochem., 136, 2014, 99-106. T.T. Morris,* J.L.A. Keir, S.J. Boshart, V.P. Lobanov, A.M.A. Ruhland and J. Gailer. Mobilization of Cd from human serum albumin by small molecular weight thiols. J. Chromatogr. B, 958, 2014, 16-21. M. Sooriyaarachchi,* A. Narendran, W.D. White and J. Gailer. Chemoprotection by D-methionine against cis-platin-induced side effects: Insight from in vitro studies using human plasma. Metallomics, 6, 2014, 532-541. M.T. Le,* M. Hassanin,* M. Mahadeo,* J. Gailer, and E.J. Prenner. Hg- and Cd-induced modulation of lipid packing and monolayer fluidity in biomimetic erythrocyte model systems. Chem. Phys. Lipids, 170-171, 2013, 46-54. J. Gailer. Metal Species in Biology: Bottom-Up and Top-Down LC Approaches in Applied Toxicological Research. ISRN Chromatography, Volume 2013, Article ID 801840, 21 pages. E.Z. Jahromi,* J. Gailer. Improved selectivity of ZnNa3DTPA vs. Na5DTPA to abstract Cd2+ from plasma proteins in vitro. Metallomics, 5, 2013, 615 - 618. M. Sooriyaarachchi,* A. Narendran, and J. Gailer. N-Acetyl-L-cysteine modulates the metabolism of cis-platin in human plasma in vitro(Front Cover). Metallomics, 5, 2013, 197-207. E.Z. Jahromi,* J. Gailer. In vitro assessment of chelating agents with regard to their abstraction efficiency of Cd2+ bound to plasma proteins. Metallomics, 4, 2012, 995-1003. M. Sooriyaarachchi,* A. Narendran, and J. Gailer. The effect of sodium thiosulfate on the metabolism of cis-platin in human plasma in vitro. Metallomics, 4, 2012, 960-967. J. Gailer. Probing the bioinorganic chemistry of toxic metals in the mammalian bloodstream to advance human health. J. Inorg. Biochem., 108, 2012, 128-132. J.D. Meers,* E.Z. Jahromi,* B. Heyne and J. Gailer. Improved RP-HPLC separation of Hg2+ and CH3Hg+ using a mixture of thiol-based mobile phase additives. J. Environ. Sci. Health., Part A, 47, 2012, 149-154. J.L. Gómez-Ariza, E.Z. Jahromi,* M. González-Fernández, T. García-Barrera and J. Gailer. Liquid chromatography-inductively coupled plasma-based metallomic approaches to probe health-relevant interactions between xenobiotics and mammalian organisms. Metallomics, 3, 2011, 566-577. S. Tuncel, F. Dumoulin, J. Gailer, M. Sooriyaarachchi,* D.Atilla, M. Durmus, D. Bouchou, H. Savoie, R.W. Boyle and V. Ahsen, A set of highly water-soluble tetraethyleneglycol-substituted Zn(II) phthalocyanines: synthesis, photochemical and photophysical properties, interaction with plasma proteins and in vitro phototoxicity (Front Cover). Dalton Trans., 40, 2011, 4067-4079. M. Sooriyaarachchi,* A. Narendran and J. Gailer, Comparative hydrolysis and plasma binding of cis-platin and carboplatin in human plasma in vitro (Front Cover). Metallomics, 3, 2011, 49-55. K.L. Pei,* M. Sooriyaarachchi,* D.A. Sherell, G.N. George and J. Gailer, Probing the coordination behavior of Hg2+, CH3Hg+, and Cd2+towards mixtures of two biological thiols by HPLC-ICP-AES. J. Inorg. Biochem., 105, 2011, 257-263.