Thomas J. Meade
Eileen M. Foell Professor of Cancer Research
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 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: Life processes are governed by an intricate orchestration of biochemical events. A goal of current research is to understand these processes in terms of molecular interactions and to develop molecular-based methods for control. Ligand-receptor thermodynamics, ligand trafficking, receptor-mediated cell response, and cell adhesion and migration are pertinent examples. The interactions between a small molecule and a large biomolecule are controlled by such forces as ionic contacts, hydrogen bonding, dipole-dipole alignment, van der Waal’s forces, and hydrophobic interactions. Electrochemistry of redox-modified monolayers is highly sensitive to these forces. Therefore we seek to use electrochemical methods to probe ligand-receptor interactions and to develop electronic protein biosensors.
Metal Complexes as Enzyme Inhibitors: The use of metals in medicine has grown impressively in recent years as the result of the enhanced 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 metal complex to mediate a specific interaction between the target protein and metal complex. 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 re-iterative approach to drug development where model compounds are tested in biological systems followed by chemical modification for further optimization of activity. This approach combines theoretical and experimental chemistry, molecular biology, developmental biology, biochemistry, and imaging.
Cobalt derivatives as promising therapeutic agents. Heffern MC, Yamamoto N, Holbrook RJ, Eckermann AL, and Meade TJ. Current Opinion in Chemical Biology. 2013 April;17(2):189-196.
Rational design of [Co(acacen)L2]+ inhibitors of protein function. Matosziuk LM, Holbrook RJ, Manus LM, Heffern MC, Ratner MA, and Meade TJ. Dalton Transactions. 2013 March;42(11):4002-4012.
Axial Ligand Exchange of N-heterocyclic Cobalt(III) Schiff Base Complexes: Molecular Structure and NMR Solution Dynamics. Manus LM, Holbrook RJ, Atesin TA, Heffern MC, Harney AS, Eckermann AL, and Meade TJ. Inorganic Chemistry. 2013 January 18;52(2):1069-1076.
Synapse-Binding Subpopulations of Aβ Oligomers Sensitive to Peptide Assembly Blockers and scFv Antibodies. Velasco PT, Heffern MC, Sebollela A, Popova IA, Lacor PN, Lee KB, Sun X, Tiano BN, Viola KL, Eckermann AL, Meade TJ, and Klein WL. ACS Chemical Neuroscience. 2012 November 21;3(11):972-981.
Kinetics and thermodynamics of irreversible inhibition of matrix metalloproteinase 2 by a Co(III) Schiff base complex. Harney AS, Sole LB, and Meade TJ. Journal of Biological Inorganic Chemistry. 2012 August;17(6):853-860.
Synthesis, Characterization, and in vitro Testing of a Bacteria-Targeted MR Contrast Agent. Matosziuk LM, Harney AS, MacRenaris KW, and Meade TJ. European Journal of Inorganic Chemistry. 2012 April;2012(12):2099-2107.
Targeted Inactivation of Snail Family EMT Regulatory Factors by a Co(III)-Ebox Conjugate. Harney AS, Meade TJ, and LaBonne C. PLoS ONE. 2012 February 29;7(2):e32318.
Specific Inhibition of the Transcription Factor Ci by a Cobalt(III) Schiff Base-DNA Conjugate. Hurtado RR, Harney AS, Heffern MC, Holbrook RJ, Holmgren RA, and Meade TJ. Molecular Pharmaceutics. 2012 February 6;9(2):325-333.
Synthesis and Biological Evaluation of Water-Soluble Progesterone-Conjugated Probes for Magnetic Resonance Imaging of Hormone Related Cancers. Sukerkar PA, MacRenaris KW, Townsend TR, Ahmed RA, Burdette JE, and Meade TJ. Bioconjugate Chemistry. 2011 November 16;22(11):2304-2316.
Three-Channel Spectrometer for Wide-Field Imaging of Anisotropic Plasmonic Nanoparticles. Sweeney CM, Nehl CL, Hasan W, Liang T, Eckermann AL, Meade TJ, and Odom TW. Journal of Physical Chemistry C. 2011 August 18;115(32):15933-15937.
A Steroid-Conjugated Magnetic Resonance Probe Enhances Contrast in Progesterone Receptor Expressing Organs and Tumors in Vivo. Sukerkar PA, MacRenaris KW, Meade TJ, and Burdette JE. Molecular Pharmaceutics. 2011 August 1;8(4):1390-1400.
Probing the Chemical Stability of Mixed Ferrites: Implications for Magnetic Resonance Contrast Agent Design. Schultz-Sikma EA, Joshi HM, Ma Q, MacRenaris KW, Eckermann AL, Dravid VP, and Meade TJ. Chemistry of Materials. 2011 May 24;23(10):2657-2664.
Polystyrene microsphere-ferritin conjugates: A robust phantom for correlation of relaxivity and size distribution. Sukerkar PA, Rezvi UG, MacRenaris KW, Patel PC, Wood JC, and Meade TJ. Magnetic Resonance in Medicine. 2011 February;65(2):522-530.
View all publications by Thomas J. Meade listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.