个人简介

B.S. Haverford College, 1995 M.S. Johns Hopkins University, 1997 Ph.D. Johns Hopkins University, 2001 (Advisor: Prof. Ken Karlin) Postdoctoral Mayo Clinic, 2001-03 (Advisor: Prof. Frank Rusnak) Postdoctoral University of California – San Francisco, 2003-06 (Advisor: Prof. Paul Ortiz de Montellano)

研究领域

Inorganic Chemistry

Research projects in the Ghiladi group focus on the multiple roles of metal ions in biology and medicine, with the goals of elucidating enzyme pathways pertinent to disease states, understanding fundamental mechanisms of metalloenzymes involved in biocatalysis, investigating the limits of protein design and engineering, and the emergence of metallodrugs in pharmaceutical chemistry. We address each of these objectives using a highly interdisciplinary approach that is unique to the bioinorganic chemist. Namely, that enzymology, spectroscopy, molecular biology, synthetic inorganic chemistry, and protein biochemistry are all integral parts of the bigger picture of how metals interact with their environment in biological systems.

近期论文

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D. Barrios, J. D’Antonio, N. L. McCombs, J. Zhao, S. Franzen, A. Schmidt, L. Sombers, and R. A. Ghiladi "Peroxygenase and Oxidase Activities of Dehaloperoxidase-Hemoglobin from Amphitrite ornata" J. Am. Chem. Soc. 2014, 136, 7914-7925. R. Dumarieh, J. D’Antonio, A. Liang, T. Smirnova, D. A. Svistunenko, and R. A. Ghiladi "Tyrosyl Radicals in Dehaloperoxidase: How Nature Deals with Evolving an Oxygen Binding Globin to a Biologically-Relevant Peroxidase" J. Biol. Chem., 2013, 288, 33470–33482. J. Zhao, V. de Serrano, R. Dumarieh, R. A. Ghiladi, M. K. Thompson, and S. Franzen "The Role of the Distal Histidine in H2O2 Activation and Heme Protection in Both Peroxidase and Globin Functions" J. Phys. Chem. B, 2012, 116, 12065-12077. D. A. Svistunenko, J. Worrall, S. Chugh, S. Haigh, R. A. Ghiladi, and P. Nicholls "Ferric haem forms of Mycobacterium tuberculosis catalase-peroxidase probed by EPR spectroscopy: their stability and interplay with pH" Biochimie, 2012, 94, 1274-1280. B. L. Carpenter, E. Feese, H. Sadeghifar, D. S. Argyropoulos, and R. A. Ghiladi "Porphyrin-Cellulose Nanocrystals: A Photobactericidal Material that Exhibits Broad Spectrum Antimicrobial Activity" Photochem. Photobiol., 2012, 88, 527-536. R. A. Ghiladi, A. L. Rheingold, M. A. Siegler, and K. D. Karlin "Synthesis and characterization of new trinuclear copper complexes" Inorg. Chim. Acta, 2012, 389, 131-137. S. Franzen, K. Sasan, B. E. Sturgeon, B. J. Lyon, B. Batternberg, H. Gracz, R. Dumarieh, and R. A. Ghiladi "Non-Photochemical Base-Catalyzed Hydroxylation of 2,6-Dichloroquinone by H2O2 Occurs by a Radical Mechanism" J. Phys. Chem. B, 2012, 116, 1666-1676. S. Franzen, M. K. Thompson, and R. A. Ghiladi "The Dehaloperoxidase Paradox" Biochim. Biophys. Acta., 2012, 1824, 578-588. E. L. D’Antonio, J. D’Antonio, V. De Serrano, H. Gracz, M. K. Thompson, R. A. Ghiladi, E. F. Bowden, and S. Franzen "Functional Consequences of the Creation of an Asp-His-Fe Triad in a 3/3 Globin." Biochem., 2011, 50, 9664-9680. E. Feese, H. Sadeghifar, H. Gracz, D. S. Argyropoulos, and R. A. Ghiladi "Photobactericidal Porphyrin-Cellulose Nanocrystals: Synthesis, Characterization and Antimicrobial Properties" Biomacromolecules, 2011, 12, 3528-3539. J. D’Antonio and R. A. Ghiladi "Reactivity of Deoxy- and Oxyferrous Dehaloperoxidase B from Amphitrite ornata: Identification of Compound II and its Ferrous-Hydroperoxide Precursor" Biochem. 2011, 50, 5999-6011. M. K. Thompson, S. Franzen, R. A. Ghiladi, B. Reeder, and D. A. Svistunenko "Compound ES of Dehaloperoxidase Decays via Two Alternative Pathways Depending on the Conformation of the Distal Histidine" J. Am. Chem. Soc., 2010, 132, 17501-17510. J. D’Antonio, E. L. D’Antonio, M. K. Thompson, E. F. Bowden, S. Franzen, T. Smirnova, and R. A. Ghiladi "Spectroscopic and Mechanistic Investigations of Dehaloperoxidase B from Amphitrite ornata" Biochem. 2010, 49, 6600-6616. V. De Serrano, J. D’Antonio, S. Franzen, and R. A. Ghiladi "Structure of Dehaloperoxidase B at 1.58 Å Resolution and Structural Characterization of the A/B Dimer from Amphitrite ornata" Acta Cryst. 2010, D66, 529-538. C. E. Cade, A. C. Dlouhy, K. F. Medzihradszky, S. P. Salas-Castillo, and R. A. Ghiladi "Isoniazid-Resistance Conferring Mutations in Mycobacterium tuberculosis KatG: Catalase, Peroxidase, and INH-NADH Adduct Formation Activities" Protein Sci., 2010, 19, 458-474. E. Feese and R. A. Ghiladi "Highly Efficient Photodynamic Inactivation of Mycobacterium smegmatis" J. Antimicrob. Chemother., 2009, 64, 782-785. J. Feducia, R. Dumarieh, L. B. G. Gilvey, T. Smirnova, S. Franzen, and R. A. Ghiladi "Characterization of Dehaloperoxidase Compound ES and its Reactivity with Trihalophenols" Biochem., 2009, 48, 995-1005. D. Maiti, J. S. Woertink, R. A. Ghiladi, E. I. Solomon, and Karlin, K. D. "Molecular Oxygen and Sulfur Reactivity of a Cyclotriveratrylene Derived Trinuclear Copper(I) Complex" Inorg. Chem., 2009, 48, 8342-8356. R. A. Ghiladi, E. Chufan, D. del Río, E. I. Solomon, C. Krebs, B. H. Huynh, H.-w. Huang, P. Moënne-Loccoz, S. Kaderli, M. Honecker, A. D. Zuberbühler, L. Marzilli, R. J. Cotter, and K. D. Karlin "Further Insights into the Spectroscopic Properties, Electronic Structure and Kinetics of Formation of the Heme-Peroxo-Copper Complex [(F8TPP)FeIII-(O22–)-CuII(TMPA)]+" Inorg. Chem., 2007, 46, 3889-3902. R. A. Ghiladi, K. F. Medzihradszky, and P. R. Ortiz de Montellano "The Role of the Met-Tyr-Trp Crosslink in Mycobacterium tuberculosis Catalase-Peroxidase (KatG) as Revealed by KatG(M255I)" Biochem. 2005, 44, 15093-15105. R. A. Ghiladi, K. F. Medzihradszky, F. M. Rusnak, and P. R. Ortiz de Montellano "Correlation Between Isoniazid Resistance and Superoxide Reactivity in Mycobacterium tuberculosis KatG" J. Am. Chem. Soc. 2005, 127, 13428-13442.