My laboratory studies the pathogenesis of diseases caused by Shiga toxins, a family of genetically and functionally related protein toxins expressed by the enteric pathogens Shigella dysenteriae type 1 and select serotypes of Escherichia coli. Shiga toxin-producing E. coli have been in the news lately as ingestion of ground beef, spinach or well water contaminated with the toxin-producing organisms has resulted in widespread outbreaks of bloody diarrhea. Unfortunately, patients with these diarrheal diseases are at increased risk for developing life-threatening extra-intestinal complications including acute renal failure and neurological abnormalities. There are several research projects ongoing in the laboratory: (i) characterization of intracellular signaling pathways activated by Shiga toxins in macrophages leading to the increased expression of proinflammatory cytokines; (ii ) characterization of toxin- induced signaling pathways leading to apoptosis; (iii) examination of the roles of proinflammatory cytokines and apoptosis in pathogenesis using a murine model of Shiga toxin-induced renal damage; (iv) characterization of the global transcriptional response of human macrophages to Shiga toxins using microarray analysis; and (v) examination of the capacity of Shiga toxins to elicit the ER stress response.
