Viswanathan Laboratory Research Interests
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.
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 mitochondrial homeostasis and host cell-cell junctions, that are perturbed during the course of an infection.
