|Steven A. Williams
Gates Professor of Biological Sciences, Smith College
Ph.D.: University of California at Davis
Molecular Biology of Human Parasitic Diseases/Genome Projects
Molecular biology research in my laboratory focuses on the nematode parasites that cause filarial disease in humans and animals. These parasites cause elephantiasis and African River Blindness in humans, and heartworm disease in dogs. Three major lines of research are currently being pursued in my laboratory: 1) As the director of the World Health Organization’s Filarial Genome Project, my laboratory is the center of this multinational project involving laboratories from Egypt, India, Uganda, Indonesia, the United States, and the United Kingdom. The main goals of this project are the identification, sequencing, and mapping of all the parasite’s genes in order to foster the development of new vaccine candidates and drug targets. 2) I also direct the Clark Foundation’s River Blindness Genome Project which has the same goals as the Filarial Genome Project. 3) Stage-specific, developmentally regulated gene expression.
Filarial parasites have an intriguing life cycle with five clear developmental stages. Some of these stages occur in the mammalian host and some occur in the insect vector that transmits the disease. We have developed cDNA libraries for all of these developmental stages and have identified numerous genes that are expressed in a stage-specific manner. Using immunohistochemistry and immunogold electron microscopy, we have also determined the precise localization of the proteins encoded by these genes. The genes and their encoded proteins that we are studying most intensely are a new class of antioxidants called thioredoxin peroxidases which appear to be the major proteins protecting the worm against host-induced free radical damage. Such knowledge will be extremely useful in the eventual identification of new vaccine candidates and drug targets to help eliminate these diseases.
Filarial Genomics: Gene Discovery and Gene Expression. S.A. Williams and S.J. Laney ; In: World Class Parasites: Volume 5, The Filaria. Ed. T.R. Klei and T.V. Rajan, Kluwer Academic Publishers, Boston, MA., p. 31-42, 2003.
Williams, S. A., S. J. Laney, M. Lizotte-Waniewski, L. Ann Bierwert and T. R. Unnasch (2002). "The river blindness genome project." Trends Parasitol 18(2): 86-90.
Kluber, S., T. Supali, S. A. Williams, E. Liebau and P. Fischer (2001). "Rapid PCR-based detection of Brugia malayi DNA from blood spots by DNA Detection Test Strips." Trans R Soc Trop Med Hyg 95(2): 169-70.
Bockarie, M. J., P. Fischer, S. A. Williams, P. A. Zimmerman, L. Griffin, M. P. Alpers and J. W. Kazura (2000). "Application of a polymerase chain reaction-ELISA to detect Wuchereria bancrofti in pools of wild-caught Anopheles punctulatus in a filariasis control area in Papua New Guinea." Am J Trop Med Hyg 62(3): 363-7.
Lizotte-Waniewski, M., W. Tawe, D. B. Guiliano, W. Lu, J. Liu, S. A. Williams and S. Lustigman (2000). "Identification of potential vaccine and drug target candidates by expressed sequence tag analysis and immunoscreening of Onchocerca volvulus larval cDNA libraries." Infect Immun 68(6): 3491-501.
Fischer, P., T. Supali, H. Wibowo, I. Bonow and S. A. Williams (2000). "Detection of DNA of nocturnally periodic Brugia malayi in night and day blood samples by a polymerase chain reaction-ELISA-based method using an internal control DNA." Am J Trop Med Hyg 62(2): 291-6.
Williams, S. A., M. R. Lizotte-Waniewski, J. Foster, D. Guiliano, J. Daub, A. L. Scott, B. Slatko and M. L. Blaxter (2000). "The filarial genome project: analysis of the nuclear, mitochondrial and endosymbiont genomes of Brugia malayi." Int J Parasitol 30(4): 411-9.
Williams, S.A., M.R. Lizotte-Waniewski, D. Guiliano, J. Daub, M.L. Blaxter, J. Foster, B. Slatko and A. L. Scott(2000)."The Nuclear, Mitochondrial and Endosymbiont Genome of Brugia malayi."Int. J. Parasitol., 30: 411-419
Unnasch, T.R. and S.A. Williams (2000)."The Genomes of Onchocerca volvulus."Int. J. Parasitol, 30: 543-552
Williams, S.A. and D.A. Johnston (1999)."Helminth Genome Analysis: the Current Status of the Filarial and Schistosome Genome Projects."Parasitology, 118: S19-S38
Williams, S.A. (1998)."Deep Within the Filarial Genome: an Update on the Progress of the Filarial Genome Project. The Filarial Genome Project:" Parasitology Today, 15: 219-224