WHAT WE DO
General description of lab outlook/philosophy
Dissection of Enteropathogenic/Enterohemorrhagic E. coli Interactions with Intestinal Epithelial Cells.
EPEC and EHEC continue to plague the developing world, with ~1 child dying every 30 seconds of infectious diarrheas caused by these organisms. There are no vaccines to prevent EPEC/EHEC infections, no robust animal models, and oral rehydration solutions (for EPEC) and antibiotic therapies (for EHEC) are not effective, or are contraindicated.
As a key virulence strategy, these pathogens manipulate epithelial cell signaling and function by delivering virulence ‘effector’ proteins into host cells via a type III secretion system. We have systematically characterized the roles of several effector proteins in EPEC/EHEC pathogenesis, and continue to study how these factors alter host cell function in a coordinated manner.
[graphic]
Novel strategies to interrogate host-pathogen interactions:
We are particularly excited about our recent work related to the use of iterative proteomic analysis, coupled with functional assays, to study host-pathogen interactions. Simply phrased, traditional approaches to understand host-pathogen interactions focus on one narrow aspect at a time, and subsequently try to fit these observations into the context of disease.
Our recent work, on the other hand, explores global changes using cutting-edge technologies and, in conjunction with traditional approaches, seeks to generate a comprehensive understanding of the disease process. To do this, we used phospho- proteomic analysis of EPEC-infected cells to define changes in host cell functions. From this broad perspective, we have been able to zero in on key pathways, such as the impact on host cell-cell junctions, that are perturbed during the course of an infection.
[graphic]
