The Markham Lab investigates C. difficile bacterial toxin pathogenesis and the mechanisms of microbially influenced colorectal cancer tumorigenesis. Our long-term goal is to understand how changes in the human microbiome affect epithelial cell signaling events and inflammatory responses in colorectal cancer. Because our interests are grounded in defining microbiological and immunological mechanisms associated with tumorigenesis and cancer progression, the VI4 is an excellent fit for our program. We recently obtained a fundable impact score on an award from the Department of Veterans Affairs. The title of this proposal is “Gastrointestinal cell type-specific signaling and C. difficile toxin pathogenesis.” A second project has gained momentum and originated as part of the Vanderbilt Colon Molecular Atlas Project (ColonMAP). Our focus is to understand how the disrupted spatial organization of the gut microbiota known as invasive biofilm formation may accelerate colorectal cancer. We have recently obtained pilot funding from the VICC Gastrointestinal SPORE program to develop a novel single-cell RNA-sequencing technology. The method uses oligonucleotide barcodes conjugated to C. difficile toxins for determining how such toxins affect pro-tumorigenic transcriptional programs in the colon. These basic science research projects ideally will form the foundation for exciting opportunities to translate discoveries into therapeutic and diagnostic strategies.

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