Autotransporters are type V secreted proteins that can be presented on the surface of bacteria, or secreted after being cleaved from the outer membrane. They are the largest family of bacteria virulence factors, and most have been characterized as adhesins and proteases. Previous studies have shown these proteins to be responsible for invoking an inflammatory response during infection. We will investigate if autotransporter adhesins and proteases could be triggering this inflammation in cancer.

Serine and cysteine protease autotransporters are a key tool that Gram-negative bacteria use for survial and infection. We will take a chemical biology approach to develop inhibitors and probes to determine if inhibiting these proteins leads to altered epithelial invasion, and if this in turn leads to a decreased prevalance of Fusobacterium being associated with the progression of colorectal cancer. Simple scaffolds will be used to develop diverse libraries that can be screened and fine tuned for specific proteins within the family.

Bacteria upregulate numerous genes during infection, and these gene patterns can be specific for the tissue that is infected. While it is known which human genes are upregulated during infection with Fusobacterium, which genes are upregulated in the bacterium have not been studied. We will use RNA-SEQ technology to determine the gene expression patterns during infection of cultured human colonocytes, as well as mouse models of infection. This data will provide us with a list of genes that are crucial for bacterial invasion, which may lead us to discover specific pathways that produce proteins or metabolites that illicit an inflammatory response.