Faculty
Thomas Meade, PhD
Professor
Chemistry, BMBCB, Neurobiology and Physiology
PhD, Ohio State University
Email: tmeade@northwestern.edu
Phone: (847) 491-2481
Fax: (847) 491-7713
Room: Tech. Rm L110
Research Interests
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.
Selected Publications
Targeted inhibition of Snail family zinc finger transcription factors by oligonucleotide-Co(III) Schiff base conjugate. Harney AS, Lee J, Manus LM, Wang P, Ballweg DM, LaBonne C, Meade TJ. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13667-72. Epub 2009 Aug 3.
Cell-permeable MR contrast agents with increased intracellular retention. Endres PJ, MacRenaris KW, Vogt S, Meade TJ. Bioconjug Chem. 2008 Oct;19(10):2049-59. Epub 2008 Sep 20.
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.
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.
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.
View publications by Thomas J. Meade listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue