Key words: enteric bacteria, enterotoxigenic Bacteroides fragilis, biofilms, epidemiology, microbiome, colon cancer, colonic mucosal inflammation, IL-17
The Sears laboratory studies how the microbiota and specific bacteria induce colon carcinogenesis. We integrate studies in humans and mouse models (including germ-free mice) employing microbiology, bioinformatics and immunologic methods to seek to achieve our goals to understand disease mechanisms and to develop new approaches to disease prevention. We study the bacterium, enterotoxigenic Bacteroides fragilis (ETBF) as a model for inducing colon inflammation and carcinogenesis. Using in vivo murine models, we identified that ETBF contributes to colon tumorigenesis through secretion of BFT (B. fragilis toxin), activation of STAT3 and NF-κB as well as induction of mucosal IL-17. In humans, most colon cancer patients have evidence of ETBF colonization and nearly 50% of individuals with sporadic colon cancers as well as individuals with hereditary colon cancer display carcinogenic biofilms. Active projects in the laboratory include determining the epidemiology of colon biofilm formation in a 2000 person prospective colonoscopy cohort; understanding how biofilms form on mucosal surfaces and induce disease; addressing mechanisms by which bacterial virulence factors induce carcinogenic DNA alterations; defining which microbiota members or communities induce mucosal carcinogenesis and IL-17; and identifying how the colon microbiome and its members impact cancer immunotherapy responses in humans.
Publications and Interests: https://jhu.pure.elsevier.com/en/persons/cynthia-louise-sears