Haslam Lab Research

Bacterial toxins, by their very nature, are remarkably adept at exploiting host cell biology. Shiga toxin (Stx), the agent studied by our laboratory, is a good example. Shiga toxin is responsible for thousands of cases of hemorrhagic enteritis annually, and is the most common cause of hemolytic uremic syndrome, a potentially fatal illness that predominantly affects young children.

Our laboratory is interested in the intracellular trafficking of shiga toxin within host cells. Using a genetic screen for molecules involved in toxin trafficking, we isolated the cDNA for a novel ER-localized chaperone, which we named HEDJ. We found that shiga toxin is capable of transport across the ER membrane after interaction with HEDJ. Apparently, shiga toxin “pretends” to be a misfolded host protein in order to exploit HEDJ and and the “ER quality-control pathway” to gain access to the cytoplasm. We are currently investigating the role of HEDJ and other chaperones in normal cellular biology as well as toxin trafficking.

More recently, we have undertaken a 'chemical genomics' approach to studying the toxin transport pathway. Using a high throughput screen developed in our laboratory, we are identifying small molecule inhibitors of Stx, ricin, and cholera toxin transport. These compounds are used as tools to dissect the toxin transport pathway and may show promise as potential therapeutic agents against these toxins.

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