UNDERSTANDING THE ROLE OF BACTERIAL OUTER MEMBRANE AND SECRETED PROTEINS IN INFECTION, CELL SIGNALLING, AND INFLAMMATORY DISEASES.

More than 15% of carcinomas can be attributed to known infectious agents such as bacteria and viruses. We are working at the interface of bioinformatics, chemistry, and biology to determine the role of the bacterial infections in inflammatory disease such as cancer, with a focus on understanding the role of surface bound and secreted virulence factors.

Fusobacterium nucleatum is a Gram-negative bacterium that is significantly overrepresented in the colonic tissue of patients with colorectal cancer, and this bacterium has an abnormally high number of genes encoding for uncharacterized virulence factors, several which belong to a family known as Autotransporters. 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 or down-regulating the human immune system during infection. We will investigate if autotransporter adhesins and proteases could be triggering this inflammation in cancer.

We are creating new genetic, biochemical, and synthetic tools to elucidate the role of these uncharacterized proteins in inflammation and cancer.