Professor, Allergy and Infectious Dis.
University of Washington
Our lab is engaged in the study of molecular biology and cellular immunology of infectious diseases, with particular interests in drug discovery, pathogenesis and protective antigens for vaccines. Towards drug discovery, we study the protozoan pathogens that cause Chagas' disease (Trypanosoma cruzi), African sleeping sickness (Trypanosoma brucei), leishmaniasis, and malaria. We use structure-based drug design, targeting enzymes of glycolysis and protein prenylation, to help find new compounds that are active against these protozoan parasites. We use molecular techniques such as genetic deletions (knock outs) and structure-activity correlations to test our hypothesis that these enzymes are good drug targets. We have developed high-throughput techniques for testing the activity of these compounds against mammalian forms of these parasites in vitro. We also have developed rodent models for testing the activity of these compounds in vivo. These studies are performed in collaboration with Wim Hol (Dept. of Biochemistry), Mike Gelb (Dept. of Chemistry), and Fred Buckner (Medicine/Infectious Diseases).
With Sheila Lukehart and Arturo Centurion-Lara (Medicine/Infectious Diseases), we are studying a polymorphic gene family of Treponema pallidum that appears to encode surface-displaced proteins. These proteins may form an antigenic variation family that may allow T. pallidum to escape the immune response and are likely to be integral in syphilis pathogenesis.
With Caroline Cameron (Medicine/Infectious Diseases) and Sheila Lukehart, we are attempting to clone genes of Treponema pallidum, whose products encode opsonic antigens. Such antigens could form the basis of a vaccine for syphilis, and indeed, immunization with several of these have been shown to be protective in the rabbit T. pallidum challenge model.