Area of Research

• Dr. Ralston's lab focuses on interactions between the microbial eukaryote Entamoeba histolytica and the human host. E. histolytica causes amoebiasis, a potentially lethal diarrheal disease in the developing world. The species was named "histolytica" (histo-: tissue; lytic-: dissolving) for its ability to injure host tissue. E. histolytica trophozoites ("amoebae") possess potent cell-killing activity that is likely to drive tissue damage, but the mechanism by which amoebae kills cells was previously unclear. We discovered that amoebae kill human cells via an unusual mechanism, in which they bite off and ingest human cell fragments that contain human cell membrane, cytoplasm, and organelles. We named this "amoebic trogocytosis" (trogo-:nibble). Trogocytosis provides a new paradigm for the pathogenesis of amoebiasis. As an unusual cell killing insult, it further provides a vehicle to uncover new host cell death and survival signaling. Unlike phagocytosis (phago-: devour), in which one cell "swallows" another, trogocytosis is poorly understood. However, there is an emerging appreciation that many eukaryotes take bites of membranes from other cells, sometimes together with intracellular contents, suggesting that this process is likely to be fundamental. Trogocytosis plays a role in signaling between immune cells, and intracellular bacteria stimulate host cell trogocytosis to promote their transfer from one cell to another. Other eukaryotic microbes use trogocytosis for cell killing, including the "brain-eating" amoeba, Naegleria fowleri. Therefore, trogocytosis might represent a conserved strategy for eukaryotic intercellular exchange that is exaggerated and exploited for cell killing by microbial pathogens. Our work is therefore broadly relevant to conserved mechanisms for eukaryotic cell-cell interaction.