David H. Thompson
Professor & University Faculty Scholar
Chemistry, College of Science
Phone: (765) 494-0386
B.S., Chemistry, University of Missouri-Columbia, 1978
B.A., Biology, University of Missouri-Columbia, 1978
Ph.D., Organic Chemistry, Colorado State University, 1984
Development of transiently-stable carrier systems for drug & gene delivery; supported membrane protein sensors for drug discovery; nanogel synthesis; 2D protein crystallization
Impact Statement & Explanation of Research:
1. Tissue-responsive carrier systems for drug and gene delivery. We are developing bioresponsive materials for drug and gene delivery. These materials are designed to promote fusion of the carrier with target cell membranes via metabolically-driven phase changes in the carrier system. Liposomes, diblock copolymer micelles, polyrotaxane:nucleic acid nanoparticles and lipoplex are used to deliver conventional chemotherapeutic agents, photodynamic agents, and water-soluble macromolecules (e.g., siRNA and plasmid DNA) upon degradation of strategically-placed vinyl ether bonds in the carrier.
2. Development of Supported Membrane Protein-Based Sensors for High-Throughput Screening. A supported lipid membrane sensor that will be capable of detecting the activity of carboxyl methyltransferase (MTase), an important target for anticancer drug discovery, is under development. Progress to date shows that we can orient the MTase with respect to the sensor surface, retain methyl transferase activity within ruggedized membranes, and detect MTase activity via fluorescence or interferometry techniques.
3. Crystallization of Proteins on Nanostructured Interfaces. We are developing methods that enable the crystallization of proteins on 1D & 2D template interfaces. A crucial material design goal is the discovery of interfaces that posses the proper balance of forces between strong adsorption and facile diffusion along the template. This has been achieved through the use of cyclodextrin-based monolayers and polyrotaxane rods that bind NTA:Ni2+:His-tag proteins via reversible host-guest interactions. We are studying how to control the site and rate of nucleation to enable the epitaxial growth of well-ordered crystals on the millimeter length scale.
List of Current Projects:
Development of an ICMT Supported Membrane Sensor
Bioresponsive Lipids for Intracellular Delivery
Polyrotaxane-Based Nanoparticles as Bioresponsive Nucleic Acid Vectors
Crystallization of His-tag Proteins on Nanostructured 1D & 2D Template Interfaces
Phi29 DNA-Packaging Motor for Nanomedicine
E. Kang, J.-w. Park, S. McClellan, J.-M. Kim, D. P. Holland, G. U. Lee, E. Franses, K. Park, D. H. Thompson, “Specific Adsorption of Histidine-Tagged Proteins on Silica Surfaces Modified with Ni2+:NTA-Derivatized Poly(ethylene glycol)”, Langmuir 2007 23, 6281-6288.
S. Loethen, J.-M. Kim, D. H. Thompson, “Biomedical Applications of Cyclodextrin-Based Polyrotaxanes”, Journal of Macromolecular Science C-Polymer Reviews 2007 47, 383-418.
D. H. Thompson, M. Zhou, J. Grey, H.-k. Kim, “Design, Synthesis and Performance of NTA-Modified Lipids as Templates for Histidine-Tagged Protein Crystallization”, Chemistry Letters 2007 36, 956-975.
G. Acharya, C.-L. Chang, D. Holland, D. H. Thompson, C. A. Savran, “Rapid Detection of S-Adenosyl Homocysteine Using Self-Assembled Optical Diffraction Gratings”, Angewandte Chemie, International Edition, 2008 47, 1051-1053.
G. Longo, D. H. Thompson, I. Szleifer, “Ligand-Receptor Interactions Between Surfaces: The Role of Binary Polymer Spacers”, Langmuir 2008 24, 10324-10333.
R. D. Wampler, D. J. Kissick, C. J. Dehen, E. J. Gualtieri, J. L. Grey, H.-F. Wang, D. H. Thompson, J.-X. Cheng, G. J. Simpson, “Selective Detection of Protein Crystals by Second Harmonic Microscopy”, Journal of the American Chemical Society 2008 130, 14076-14077.
J. A. Boomer, M. M. Qualls, H. D. Inerowicz, R. Haynes, G. V. Patri, J.-M. Kim, D. H. Thompson, “Cytoplasmic Delivery of Liposomal Contents Mediated by an Acid-Labile Cholesterol-Vinyl Ether-PEG Conjugate”, Bioconjugate Chemistry, in press.