Our laboratory studies the role of the inflammatory response to specific bacterial and plant toxins including Shiga toxin, produced by the deadly E. coli pathogen O157:H7 and the select agent ricin. Our goals are to understand the specific pro-inflammatory signaling pathways activated by these toxins, and to assess whether targeting inflammation by the toxins can be used as a therapeutic strategy to treat and/or prevent disease by these deadly agents.
Shiga toxin
Shiga toxin producing Eshcerichia coli (STEC) is a major cause of food-borne disease and results in significant morbidity and mortality worldwide. Severe diseases caused by STEC include hemorrhagic colitis and the hemolytic uremic syndrome (HUS), which is the leading cause of kidney failure in children in the United States. Other than supportive care there are no approved therapies for HUS, and the mechanisms by which Shiga toxin promotes HUS is poorly understood.
Together with our collaborators, we have demonstrated that Shiga toxins induce inflammatory signaling at least in part through an innate pro-inflammatory signaling pathway termed the ribotoxic stress response (RSR). Our current research aims at identifying the signaling intermediaries of this pathway, and to determine whether blocking this stress response can be used as a strategy to treat and/or prevent HUS.
Ricin toxin
As with Shiga toxin, the plant toxin ricin induces the RSR. Ricin is a select agent and bioterror threat for which no specific therapies exist. Because ricin damages cells in a manner identical to that of Shiga toxin, we have been interested in applying the knowledge gained through Shiga toxin research to the development of therapies to treat ricin-mediated disease.
Additional Research
Our laboratory also studies changes in the intestinal ecosystem during disease, with the aim of understanding how changes in this ecosystem may contribute to and/or act as a prognostic indicator of disease. As the gut ecosystem is important to proper immune function and well-being, we are conducting studies to identify how probiotic organisms are able to modulate immune function.