Thomas Meade / Professor / Chemistry / BMBCB / Neurobiology and Physiology / PhD, Ohio State University
tmeade@northwestern.edu
(847) 491-2481
(847) 491-7713
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Our research focuses on inorganic coordination chemistry for the study of molecular imaging of in vivo gene expression and intracellular messengers, transition metal enzyme inhibitors, and electronic biosensors. The design, synthesis and physical properties of transition metal and lanthanide coordination complexes are the foundation of our research efforts and can be divided into the three areas: Biological Molecular Imaging: We design and synthesize spectroscopic and magnetic probes that incorporate novel functionality for magnetic resonance and fluorescence in vivo microscopic imaging of biological systems. Particular emphasis is on answering questions about gene expression, nerve patterning, regulation of cell lineage, and DNA transfection. In order to understand how assemblies and patterns of cells in developing tissues originate from an initially homogeneous state we employ optical and magnetic resonance imaging (MRI) techniques that are enhanced by the development of contrast agents to understand these processes. The goal of this work is to develop new classes of biochemically activated contrast agents capable of reporting on the anatomical and physiological function of cellular processes in experimental animals.

Electron Transfer Mechanisms: We are investigating long-range electronic coupling through stacked, p-unsaturated systems such as DNA. Long-range intramolecular electron transfer in protein-protein complexes and modified proteins has been shown to take place over appreciable distances at biologically significant rates. Experiments have confirmed the free energy and distance dependent nature of this process as well as the importance of inner shell and solvent nuclear reorganization. A barrier to the further understanding of the factors that influence the mechanisms of long-range electron transfer is the development of an architecture capable of critically testing these properties. Our efforts are focused on understanding long-range electronic coupling interactions in DNA and biopolymers and the development of electronic biosensors.

Metal Complexes as Enzyme Inhibitors: The use of metals in medicine has grown impressively in recent years as the result of a greatly advanced understanding of the structures of biologically active metal complexes and metal-containing proteins. This area of research focuses on the interaction of inorganic therapeutic agents that can be specifically coupled to a biologically active site by cooperative redox-binding ligation. The strategy employs a series of transition metal complexes capable of irreversible inactivation of a selected enzymatic target and will be used in the development of new classes of therapeutic antitumor and antiviral agents. This work involves a two-pronged approach that is based on our ability to design site-specific ligands and then to fine tune the redox potentials of the reagent.

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Urbanczyk-Pearson, L.M, Meade, T.J., "Synthesis of a series of MRI Contrast Agents activated by ¾-Galactosidase." Nature Protocols, 2008, 3, 341-350.

Wang, P., Miller, J.E., Henling, L.M., Stern, C.H., Frank, N.L., Eckermann, A., Meade, T.J., "Synthesis and Characterization of Ruthenium and Rhenium Nucleosides." Inorg. Chem., 2007, 46,9853-9862.

Karfeild, L., Bull, S.R., Davis, N.E., Barron,A.E., Meade, T.J., "Use of a Genetically Engineered Protein for the Design of a Multivalent MRI Contrast Agent." Bioconjugate Chem. 2007, 18, 1697-1700.

Endres, P., Paunesku, T., Woloschak, G.E., Meade,T.J., "DNA-TiO2 Nanoconjugates Labeled with MR Contrast Agents." J. Am. Chem. Soc., 2007, 129, 15760-15761.

Urbanczyk-Pearson, L.M., Femia, F.J., Smith, J., Parigi, G., Eckermann, A.L., Duimstra, J.A., Luchinat, C., Meade, T.J., "Mechanistic Investigation of ¾-Galactosidase-Activated MR Contrast Agents." Inorg. Chem., 2008, 47, 56-68.

Frullano, Luca; Meade, T.J., "Multimodal MRI Contrast Agents." J. Biol. Inorg. Chem. 2007,12, 939-949.

Aslam, M.; Schultz, E.A., Sun,T., Meade, T.J., ;Dravid, P., "Synthesis of Amine-Stabilized Aqueous Colloidal Iron Oxide Nanoparticles." Crystal Growth & Design, 2007, 7, 471-475.

Major J.L., Parigi G., Luchinat, C., Meade T.J., "The synthesis and in vitro testing of a zinc-activated MRI contrast agent." Proc. Natl. Acad. Sci. USA, 2007, 104, 13881-13886.

Lee, J., Burdette, J. E., MacRenaris, K.W., Mustafi, D., Woodruff, T.K., Meade, T.J., "Rational Design, Synthesis, and Biological Evaluation of Progesterone-Modified MRI Contrast Agents." Chemistry & Biology 2007,14, 824-834.

Brekke, C.; Morgan, S. C.; Lowe, A. S.; Meade, T. J.; Price, J.; Williams, S. C. R.; Modo, M., The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry NMR Biomed. 2007, 20, (2), 77-89.

Aslam, M.; Schultz, E. A.; Sun, T.; Meade, T.; Dravid, V. P., Synthesis of Amine-Stabilized Aqueous Colloidal Iron Oxide Nanoparticles Cryst. Growth Des. 2007, 7, (3), 471-475.

Frullano, L.; Tejerina, B.; Meade, T. J., Synthesis and Characterization of a Doxorubicin-Gd(III) Contrast Agent Conjugate: A New Approach toward Prodrug-Procontrast Complexes Inorg. Chem. 2006, 45, (21), 8489-8491.

Endres, P., J.; Macrenaris, K., W.; Vogt, S.; Allen, M., J.; Meade, T., J., Quantitative imaging of cell-permeable magnetic resonance contrast agents using x-ray fluorescence Mol. Imaging 2006, 5, (4), 485-97.

Duimstra, J. A.; Stern, C. L.; Meade, T. J., Magnetic and structural properties of a cyano-bridged 1D ruthenium(III)-nickel(II) coordination polymer Polyhedron 2006, 25, (14), 2705-2709

Frullano L, Tejerina B, Meade TJ. “Synthesis and characterization of a doxorubicin – Gd (III) contrast agent conjugate: A new approach toward prodrug-procontrast complexes.” Inorganic Chemistry, 2006: 45, 8489-8491.

Endres PJ, MacRenaris KW, Vogt S, Allen MJ. Meade TJ. “Cell Permeability of MR Contrast Agents Coupled to Cell Transport Vehicles." Mol. Img. 2006: 5, 485-497.

Duimstra JA, Stern CL, Meade TJ. “Magnetic and Structural Properties of a Cyano-Bridged 1- D Ruthenium(III)-Nickel(II) Coordination Polymer.” Polyhedron, 2006: 14, 2705-2709.

Bull, S. R.; Meade, T. J.; “Magnetic Resonance Imaging of Self-Assembled Biomaterial Scaffolds.” Bioconjugate Chemistry, 2005: Vol. 16 (6), 1343-1348.

Duimstra, J. A., Femia, F. J., Meade, T. J. ” A Gadolinium Chelate for Detection of -Glucuronidase: A Self-Immolative Approach.” J. Am. Chem. Soc., 2005: 127(37) 12847-12855. 

Lee, J., Zylka, M. J., Anderson, D. J., Burdette, J. E., Woodruff, T. K., Meade, T. J. “A Steroid-Conjugated Contrast Agent for Magnetic Resonance Imaging of Cell Signaling.” J. Am. Chem. Soc. (Communication), 2005: 127(38), 13164-13166.

Eckermann, A. L., Barker, K., Hartings, M., Ratner, M., Meade, T. J. "Synthesis and Electrochemical Characterization of a Transition Metal-Modified Ligand-Receptor Pair." J. Am. Chem. Soc., 2005: 127(34), 11880-11881.

Frank, N., Meade, T.J., “Donor-Acceptor Modification of Oligonucleotides with High and Low Potential Transition Metal Complexes.” Inorganic Chemistry, 2003, 42, 1039-1044.

Modo, M., Cash, D., Mellodew. K., Steven C.R. Williams. SCR., Fraser, S.E., Meade, T.J.,Price, J., Hodges, H., “Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging.” Neuroimage, 2002 17, 803-811.

Louie, A., Dumistra, J., Meade, T.J., "Mapping Gene Expression by MRI" in BRAIN MAPPING: The Methods, Elsevier Science (USA) (J. Mazziota, A. Toga ed). 2002, 819-828.

Li, W., Giacomo, P., Fragai, M., Luchinat, C., Meade, T.J., “Mechanistic Studies and NMR Structure of a Calcium Sensitive MR Contrast Agent.” Inorganic Chemistry, 2002, 41, 4018-4024.

Huber, M., Louie, A., Ahrens, E., Jacobs, R.E., Fraser, S.E., Meade, T.J., "In-vivo Visualization of Gene Expression by Magnetic Resonance Imaging." Nature Biotechnology, 2000, 18, 321-325.

Rack, J.R., Krider, E.K., Meade, T.J., "Spectroscopy and Electrochemistry of Ruthenium-Modified Nucleic Acids: Design of a Novel Metal-Binding Nucleoside." Journal of the American Chemical Society, 2000, 122, 6287-6288.

Louie, A., Meade, T.J., "Metal Complexes as Enzyme Inhibitors." Chemical Review, 1999, 99, 2711-2734

Li, W.H., Meade, T.J. "A Calcium Sensitive Magnetic Resonance Imaging Contrast Agent." Journal of the American Chemical Society, 1999, 121, 1413-1414.

View all publications by publications by Thomas J. Meade listed in the National Library of Medicine (PubMed).
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