Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer and the second most frequent cause of cancer-related deaths in the United States. The intestinal microbiota plays an integral role in host development and immunity and has been recognized as a key component in the progression of CRC, but the mechanistic roles of the microbiota in tumor progression are poorly understood. While CRC is thought to arise primarily from genetic mutations in the host, several species, including Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli have been linked to tumor progression. However, community-level processes including horizontal gene transfer and differences in microbiota composition between individuals have complicated rigorous identification of causal associations.
Working with the Subree lab, we are using chemically-, genetically-, and othotopically-induced CRC mouse models to study the role of the microbiota in tumor progression and resolve mechanistic relationships. We are using human microbiota associated mouse models to recolonize lab mice with intestinal microbiota from patients with colorectal cancer to demonstrate and characterize the role of whole microbial communities in cancer progression. We hope to develop personalized, fecal avatar mice that can be used to test chemo-, immuno-, and microbiota-therapeutic interventions as well as to identify diagnostic signatures among the microbiome.
In August 2018, we received funding for this work through the Chainbreaker mechanism from the Masonic Cancer Center.
Recent Publications
- Yuan C, Graham M, Staley C, Subramanian S. 2020. mSystems. Mucosal microbiota and metabolome along the intestinal tract reveal a location-specific relationship. doi:10.1128/mSystems.00055-20.