Research & Publications
We are interested in understanding the mechanism of action of proteins involved in cancer, inflammation, and infectious disease using a variety of techniques including structural biology, yeast and mouse genetics, high throughput screening, and signal transduction. For example, we determined the three-dimensional structure of human, murine, and herpesvirus-8 chemokines are now determining how these proteins interact with their G-protein coupled receptor to develop a therapeutic target for oncology. We have been using macrophage migration inhibitory factor (MIF) from various pathogens to develop vaccine. We used small molecule inhibitors and are studying using some of them as reagents for probing signaling and others as therapeutics in mouse models of autoimmunity, inflammation, or infectious diseases.
Specialized Terms: Cancer; Inflammation; Infectious disease; Structural Biology; Signaling pathways; Drug design; High throughput screening (HTPS)
Extensive Research Description
We are generally interested in understanding the biology, structure, mechanism of action, and pharmacology (inhibition) of proteins in physiology and pathophysiology. Our studies are multidisciplinary and include structural biology (X-ray crystallography or NMR), molecular dynamics, high throughput screening (HPTS) and/or inhibitor design, mutational analysis, the use of strains of yeast expressing functional chemokine receptors for signaling and HTPS, and Crispr/Cas mice as a model system for models of disease.
Specific projects include:
1. Chemokine-chemokine receptor (GPCR) structures
2. High throughput screening to identify small molecule agonists and antagonists of chemokines and their GPCR receptors
3. Yeast genetics to identify and quantitate chemokine-chemokine receptor interactions
4. Mechanism of receptor activation for macrophage migration inhibitory factor
5. Identification of the substrate of MIF and structure of MIF-ligand complexes
6. Study of antagonists receptors in disease models
7. Co-crystal structures of other protein-inhibitors complexes
Education; Immune System Diseases; Inflammation; Neoplasms; Parasitic Diseases; Pharmacology; Crystallography, X-Ray; Enzymes and Coenzymes; High-Throughput Screening Assays