6104 Marsico Hall
Mechanisms underlying host:microbiota interactions in inflammation-associated digestive diseases
My primary research interest is to understand specific mechanisms by which inflammation-associated alterations to the gut microbiota influence neoplasia and tissue remodeling. My laboratory investigates how the functional capabilities and molecular features of resident microbes impact mucosal colonization, inflammatory bowel diseases (IBD), and inflammation-associated pathologies including fibrosis and tumorigenesis. The microbe we primarily focus on is adherent-invasive E. coli (AIEC), a pathovar linked to IBD and cancer. We are particularly interested in how E. coli-derived small molecules impact digestive disease. One metabolite of interest is colibactin, a genotoxin produced by some intestinal E. coli that we first described can induce DNA damage that promotes colorectal cancer. Another metabolite of interest is the siderophore yersiniabactin, which we have shown can induce microbiota-mediated fibrotic remodeling in the inflamed intestines.
Our approaches combine microbiology, immunology, genomics, bioinformatics, and gnotobiotic mouse models to identify inflammatory, pro-carcinogenic, and pro-fibrotic resident intestinal bacteria and define mechanisms by which these bacteria promote disease. The goal of this research is to define functional capabilities, microbial genes and pathways that are causally and mechanistically linked to human gastrointestinal disease. These studies will contribute essential knowledge required for the development of therapeutic tools to manipulate the intestinal microbiota and alleviate human digestive disease.