Faculty
Thomas J. Meade, PhD
Eileen M. Foell Professor of Cancer Research
Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering, and Radiology
PhD, Ohio State University
Email: tmeade@northwestern.edu
Phone: (847) 491-2481
Fax: (847) 491-3832
Room: Silverman Hall Room 2504
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: 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.
Selected Publications
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 January 3 (Epub ahead of print).
Kinetics and thermodynamics of an irreversible CO(III) Schiff base complex protein inhibitor with matrix metalloproteinase-2. Harney AS, Sole LB, and Meade TJ. Journal of Biological Inorganic Chemistry. 2012, in press.
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. 2011, in press.
In Vivo Inactivation of Core EMT Regulatory Targeted Co(III)Ebox Conjugate. Harney AS, LaBonne C, and Meade TJ. PLoS ONE. 2011, in press.
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. PMCID: PMC3148317
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. PMCID: PMC3097046
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.
Highly dispersible, superparamagnetic magnetite nanoflowers for magnetic resonance imaging. Hu F, MacRenaris KW, Waters EA, Schultz-Sikma EA, Eckermann AL, and Meade TJ. Chemical Communications. 2010;46(1):73-75.
Electrochemistry of redox-active self-assembled monolayers. Eckermann AL, Feld DJ, Shaw JA, and Meade TJ. Coordination Chemistry Reviews. 2010 August;254(15-16):1769-1802.
Molecular imaging of in vivo gene expression. Harney AS and Meade TJ. Future Medicinal Chemistry. 2010 March;2(3):503-519.
Gd(III)-Nanodiamond Conjugates for MRI Contrast Enhancement. Manus LM, Mastarone DJ, Waters EA, Zhang XQ, Schultz-Sikma EA, Macrenaris KW, Ho D, and Meade TJ. Nano Letters. 2010 February 10;10(2):484-489.
Chiral porphyrazine near-IR optical imaging agent exhibiting preferential tumor accumulation. Trivedi ER, Harney AS, Olive MB, Podgorski I, Moin K, Sloane BF, Barrett AGM, Meade TJ, and Hoffman BM. PNAS. 2010 January 26;107(4):1284-1288.
Ultrasmall, Water-Soluble Magnetite Nanoparticles with High Relaxivity for Magnetic Resonance Imaging. Hu F, MacRenaris KW, Waters EA, Liang T, Schultz-Sikma EA, Eckermann AE, and Meade TJ. Journal of Physical Chemistry C. 2009 December 10;113(49):20855-20860.
Multimodal Gadolinium-Enriched DNA-Gold Nanoparticle Conjugates for Cellular Imaging. Song Y, Xu X, MacRenaris KW, Zhang XQ, Mirkin CA, and Meade TJ. Angewandte Chemie Int Ed (English). 2009 November 16;48(48):9143-9147.
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, and Meade TJ. PNAS. 2009 August 18;106(33):13667-13672.
View all publications by Thomas J. Meade listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue.