Entamoeba histolytica is a protozoan infecting up to 10% of the human population and causing approximately 50 million cases of invasive colitis each year. Infection begins with the ingestion of the parasite1s cyst form, which transforms into the disease-causing ameboid trophozoite in the colon. Reconversion of trophozoites into the infective cyst completes the life cycle. Primarily, we study cyst formation at the protein and gene expression levels to identify cyst-inducing conditions and the parasite products which sense these conditions. Using a reptilian Entamoeba parasite, which readily encysts in vitro, we apply several approaches to isolate genes and their products which are expressed during cyst formation. We also explore culture conditions which induce excystation, and we are developing a DNA transfection system; both will permit a detailed study of gene expression during the complete parasite life cycle. We will use information from this model system to target future studies of therapies that will hopefully interrupt progression of the E. histolytica life cycle.

Another interest is a peculiar type of sialidase expressed by the parasite Trypanosoma cruzi. This enzyme can remove sialic acid from the terminal position of a glycoconjugate and reattach the sugar to another galactose-terminated carbohydrate molecule. The enzyme thus functions as a sialidase, similar to viral and bacterial enyzmes, and as a glycosyltransferase that uses preformed carbohydrate molecules as substrates. We are conducting structure and function studies of this trans-sialidase to map the enzymatic domain required for the unique sialic acid transferase function.