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.
Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent. MacRenaris KW, Ma Z, Krueger RL, Carney CE, and Meade TJ. Bioconjugate Chemistry. 2016 February 17;27(2):465-473.
Targeted delivery of gold nanoparticle contrast agents for reporting gene detection by magnetic resonance imaging. Vistain LF, Rotz MW, Rathore R, Preslar AT, and Meade TJ. Chemical Communications. 2016 January 4;52(1):160-163.
DNA–gadolinium–gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells. Nicholls FJ, Rotz MW, Ghuman H, MacRenaris KW, Meade TJ, and Modo M. Biomaterials. 2016 January;77:291-306.
Enabling non-invasive assessment of an engineered endothelium on ePTFE vascular grafts without increasing oxidative stress. Jiang B, Perrin L, Kats D, Meade T, and Ameer G. Biomaterials. 2015 November;69:110-120.
Tuning Cobalt(III) Schiff Base Complexes as Activated Protein Inhibitors. Heffern MC, Reichova V, Coomes JL, Harney AS, Bajema EA, and Meade TJ. Inorganic Chemistry. 2015 September 21;54(18):9066-9074.
Targeted Inhibition of Snail Activity in Breast Cancer Cells by Using a CoIII-Ebox Conjugate. Vistain LF, Yamamoto N, Rathore R, Cha P, and Meade TJ. ChemBioChem. 2015 September 21;16(14):2065-2072.
Water-soluble lipophilic MR contrast agents for cell membrane labeling. Carney CE, MacRenaris KW, and Meade TJ. Journal of Biological Inorganic Chemistry. 2015 September;20(6):971-977.
Multimeric Near IR-MR Contrast Agent for Multimodal In Vivo Imaging. Harrison VSR, Carney CE, MacRenaris KW, Waters EA, and Meade TJ. Journal of the American Chemical Society. 2015 July 22;137(28):9108-9116.
Nanodiscs as a Modular Platform for Multimodal MR-Optical Imaging. Carney CE, Lenov IL, Baker CJ, MacRenaris KW, Eckermann AL, Sligar SG, and Meade TJ. Bioconjugate Chemistry. 2015 May 20;26(5):899-905.
High Relaxivity Gd(III)-DNA Gold Nanostars: Investigation of Shape Effects on Proton Relaxation. Rotz MW, Culver KSB, Parigi G, MacRenaris KW, Luchinat C, Odom TW, and Meade TJ. ACS Nano. 2015 March 24;9(3):3385-3396.
Graphene Oxide Enhances Cellular Delivery of Hydrophilic Small Molecules by Co-incubation. Hung AH, Holbrook RJ, Rotz MW, Glasscock CJ, Mansukhani ND, MacRenaris KW, Manus LM, Duch MC, Dam KT, Hersam MC, and Meade TJ. ACS Nano. 2014 October 28;8(10):10168-10177.
A multimeric MR-optical contrast agent for multimodal imaging. Harrison VSR, Carney CE, MacRenaris KW, and Meade TJ. Chemical Communications. 2014 October 9;50(78):11469-11470.
Progesterone-Targeted Magnetic Resonance Imaging Probes. Townsend TR, Moyle-Heyrman G, Sukerkar PA, MacRenaris KW, Burdette JE, and Meade TJ. Bioconjugate Chemistry. 2014 August 20;25(8):1428-1437.
View all publications by Thomas J. Meade listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.