Apicomplexan parasites like Toxoplasma gondii inject hundreds of foreign components into the host cytosol that have sophisticated mechanisms of intersecting host signaling pathways and are required for parasite survival and virulence. This implies that there has been a along evolutionary history between parasites and mammalian hosts, including rodents and humans, and suggests that there ought to be innate immune sensors designed to detect the parasite directly and engage an immune response to the parasite. As a post doc in the Boothroyd lab I have identified NLRP1 as a sensor for Toxoplasma infection that limits parasite growth and dissemination in mice, rats and humans.
Toxoplasma is contracted by ingesting parasite cysts which invade the host in the small intestine. Interestingly, differences in immune response established early in infection may play a role in determining long term out come of disease. In addition to defining the molecular mechanisms of innate immune activation, I am looking at the relationship between parasite, commensal microbiota and the host immune system in determining health status during chronic infection.
As a graduate student I studied with Dr. Gregory Barton at UC Berkeley to determine how nucleic acid sensing Toll-like receptors (TLR7 and TLR9) discriminate between host- and pathogen-derived nucleic acids. The specificity for DNA and RNA come at the inherent risk of autoimmunity. To limit this cost, activation of TLR7 and TLR9 is limited to the endosomal compartments by a requirement for processing by endosomal proteases. We think that this limits potential for recognition of self-nucleic acids which are sometimes released by dying or damaged cells into the extracellular space, linking activation to compartments where freshly release nucleic acids from captured pathogens may be more abundant.
Honors & Awards
Outstanding Postdoctoral Mentor Award, Stanford Immunology (2011-2012)
Dennis and Marsha Dammerman Fellow, Damon Runyon Cancer Research Foundation (2011-2014)
Boards, Advisory Committees, Professional Organizations
Organizer, Symposium for Immunity and Pathogenesis (2012 - 2012)
Retreat Planning Committee, Microbiology and Immunology (2013 - Present)
Doctor of Philosophy, University of California Berkeley (2010)
John Boothroyd, Postdoctoral Faculty Sponsor