Kalman Lab
Research Program

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The general goal of our laboratory is to understand how bacterial and viral pathogens interface with the host. We have focused on two mechanistic aspects of this interface: (i) the immunological detection and clearance of the infection, and (ii) host systems utilized by the pathogen to facilitate infection. Our work has focused on two pathogens: enteropathogenic E.coli (and the related enterohemmorhagic E. coli, the cause of "raw hamburger disease), and vaccinia virus (a relative of variola virus, the cause of smallpox). We have utilized a combination of experimental approaches including cell biology assays based on high resolution deconvolution microscopy, biochemical systems that permit reconstitution of cellular responses with cytoplasmic extracts in permeablized cells, mouse genetic systems that model human disease, and permit investigation of the immunological response to the pathogen, and a C. elegans model system which allows genetic dissection of both host and pathogen. A long-term goal of the laboratory is to develop approaches that will permit identification of agents useful in treating disease. There is considerable impetus for developing such agents to treat infections caused by bacterial and viral pathogens: development of resistance to antibiotic or other chemotherapies looms as perhaps the single most important public health concern confronting humans in the coming century. In this regard, our current efforts have led to the development and testing of novel inhibitors of pathogenic E.coli infections, which interfere with the interface between host and pathogen but not with bacterial growth. As such, these inhibitors will not easily engender development of drug resistance.

 

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