Primary AppointmentMedicine- Infectious Diseases and International Health
Division of Infectious Diseases
Charlottesville, VA 22908
Immune mechanisms of defense against enteric (diarrheal) infections
William A. Petri, Jr., M.D., Ph.D. studies immunology and molecular pathogenesis of enteric infections and their consequences. The scope of research includes molecular parasitology of Entamoeba, innate immune host defense against Clostridium difficile, and in Bangladesh acquired immunity to Cryptosporidium. We study infections in mouse models, in humans (including clinical trials) and at the lab bench. AMEBIASIS: Focusing on amebic colitis, his lab identified the Gal/GalNAc-binding lectin of the parasite Entamoeba histolytica that mediates contact-dependent killing of host cells. Cell biologic studies of adherence, apoptosis and endocytosis of human cells by the parasite are active areas of investigation. This work is supported by an R01 to Dr. Petri from the NIH. DNA transformation of the parasite was pioneered in the lab, and is used to study molecular pathogenesis. Clinically, the group has developed FDA-approved antigen-detection tests that allow sensitive and specific diagnosis of amebiasis. Current work is focused on the mechanism of Entamoeba killing of host cells by a unique process called trogocytosis (Ralston KD et al, Nature (2014) 508:526) and the development of an amebiasis vaccine in partnership with the Infectious Diseases Research Institute of Seattle (Abhyankar M et al. Vaccine 35 (2017) 916). C. DIFFICILE: The innate immune response to Clostridium difficile colitis is a new area of investigation. Also supported by a separate R01 to Dr. Petri from the NIH, his lab has discovered that eosinophils protect from C. difficile in both mice (Buonomo EL et al., Cell Reports 2016, 16:1-12) and humans (Kulaylat AS et al., JAMA Surg. doi:10.1001/jamasurg.2018.3174.) Understanding how eosinophils protect, and why inflammasome activation by toxin activation of TLR2 causes death (Cowardin CA et al. Nature Microbiology 2016, doi:10.1038/nmicrobiol.2016.108) are current ares of focus. CRYPTOSPORIDIOSIS: The acquired immune response to Cryptosporidium hominis in children growing up in the urban slums of Bangladesh is a third area of investigation. Supported by another NIH R01 grant, the focus of this research is the role of mucosal immunity in defense, including identification of parasite proteins recognized by IgA and by immune T cells (Steiner KL et al Clin Infect Dis. 2018 Apr 20. doi: 10.1093/cid/ciy310). 19 graduate students have received the PhD degree under Dr. Petri?s mentorship all of whom continue in science, and 25 postdoctoral fellows. Eleven graduates of the lab have received K career development awards from the NIH, and nine have received their own independent R01. Currently there are five graduate students three postdoctoral fellows and 6 faculty conducting research in the Petri group.