University of Virginia Health System

William A. Petri, Jr., M.D., Ph.D.

M.D., Ph.D. Microbiology, University of Virginia 

Research Interests

Entamoeba histolytica is a parasite that destroys host immune cells via contact-dependent cytolysis. No vaccine is available to prevent the approximately 50 million illnesses and 100,000 deaths annually from amebiasis. My laboratory has established at a molecular level the parasite's mechanisms of adherence to, and invasion through, the colonic epithelium. This has included the identification and purification of the amebic galactose-specific adherence lectin. This lectin is absolutely required for the contact-dependent killing of host cells for which the organism is named. We have identified colonic mucin glycoproteins as its ligand, and showed that the lectin is a protective antigen in an animal model of amebiasis. The 170 kDa and 35 kDa lectin subunits have been sequenced and expressed, and the active carbohydrate recognition site identified. We are beginning to decipher the process by which the parasite kills the host, demonstrating a bcl-2 - independent apoptotic death pathway activated in the host at the level of caspase 3. The recent development of DNA transfection and expression systems for the parasite by my lab has enabled a reverse genetic approach to the study of amebic killing of the host. Currently our group is concentrating on the study of novel aspects of transcriptional control of lectin gene expression, the identification of domains of the lectin involved in adherence and cell killing, and the application of this information to mucosal vaccine design. These laboratory-based studies are complemented by field studies in Bangladesh, where we are investigating the human immune response to E. histolytica, and identifying strain-associated differences in E. histolytica virulence.