Cancer Prevention and Control
Area of Interest
The risk of colon cancer is 3-4x greater in individuals with chronic inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) affecting the colon. The reasons for this increased risk are not entirely clear, but may be due to inflammation-associated reactive oxygen species and epithelial proliferation. Therefore, the risk of colitis associated cancer may be reduced by effectively treating the inflammatory cascade.
Resident intestinal (non-pathogenic) bacteria contribute to the initiation of chronic colitis, but their role in the perpetuation of inflammation is less clear. Moreover, the effects of host inflammation on resident bacterial physiology and virulence are unknown. We hypothesize that resident intestinal bacteria dynamically respond to intestinal inflammation in a manner that perpetuates or worsens disease. For instance, bacterial antigens and adjuvants initiate intestinal inflammation, which in turn leads to the production of mediators including reactive oxygen species, inflammatory cells, and cytokines that consequently enhance the growth and virulence of the bacteria.
Exploring this hypothesis will enhance our understanding of the pathogenesis of inflammatory bowel diseases and colitis associated cancer.
Our lab focuses on the following main projects:
- Identification of inflammation-associated transcriptional responses in commensal intestinal bacteria during experimental colitis that impact the course of disease. We use a combination of gnotobiotic (defined microbial environment) technology in mice, molecular biology, bacterial mutagenesis, dietary interventions, microarrays, microbial RNA-Seq, and ex-vivo immune cell assays to identify bacterial genes that are differentially expressed during inflammation and mechanisms of how these genes affect host immune responses and colitis associated cancer.
- Characterize how experimental colitis impacts the genetic microevolution of commensal intestinal bacteria. We use gnotobiotic technology in mice, next generation bacterial genome sequencing, bacterial mutagenesis, high throughput bacterial phenotyping assays, and redox chemistry to identify genetic mutations that accumulate in bacteria during colitis, characterize their effect on protein function and bacterial physiology, and ultimately how mutations affect the growth and virulence of resident intestinal bacteria during experimental colitis.