Wesley C. Van Voorhis MD/PhD

Wesley C. Van Voorhis MD/PhD
Associate Professor;
Adjunct Associate Professor
Email: click here
Phone: (206) 543-0821

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.

Drug Development for Trypanosoma cruzi infections.

Cameron CE, Castro C, Lukehart SA, Van Voorhis WC. Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subsp. pallidum Tp92. J Infect Dis 181:1401-13, 2000.

Buckner FS, Eastman RT, Nepomuceno-Silva JL, Speelmon EC, Myler PJ, Van Voorhis WC, Yokoyama K. Cloning, heterologous expression, and
substrate specificities of protein farnesyltransferases from Trypanosoma cruzi and Leishmania major. Mol Biochem Parasitol 122:181-8, 2002.

Morgan CA, Molini BJ, Lukehart SA, Van Voorhis WC. Segregation of B and T cell epitopes of Treponema pallidum repeat protein K to variable
and conserved regions during experimental syphilis infection. J Immunol 169:952-7, 2002.

Gelb MH, Van Voorhis WC, Buckner FS, Yokoyama K, Eastman R, Carpenter EP, Panethymitaki C, Brown KA, Smith DF. Protein farnesyl and N-myristoyl transferases: piggy-back medicinal chemistry targets for the development of antitrypanosomatid and antimalarial therapeutics. Mol Biochem Parasitol 126:155-63, 2003.