Nicholas O. Markham, M.D., Ph.D
Assistant Professor of Medicine, Assistant Professor of Pathology, Microbiology, & Immunology Division of Gastroenterology, Hepatology, & Nutrition Staff Physician, TVHS-Veterans Affairs, Nashville
Dr. Markham is a newly appointed Assistant Professor of Medicine in the Division of Gastroenterology, Hepatology, and Nutrition with a secondary appointment in the Department of Pathology, Microbiology, and Immunology. He is a Staff Physician at the Nashville VA in Gastroenterology. His basic science laboratory is investigating the mechanistic relationships between colonic microbes and host cells. He uses in vivo approaches spanning mouse models of gastrointestinal infections to colorectal cancer and 3-dimensional human organoid tissue culture to understand how keystone bacterial species dysregulate host epithelial cell homeostasis. Specifically, these endeavors have developed from his post-doctoral fellowship with Dr. Borden Lacy and Dr. Robert Coffey in a project focused on determining how C. difficile toxin B (TcdB) transactivates colonic growth factor signaling pathways during pathogenesis. His preliminary data are the foundation for his current VA Career Development Award. The long-term goal is to reveal targets for therapeutic or preventive strategies that interdict C. difficile pathogenesis.
Dr. Markham has collaborated with Dr. Cindy Sears and Dr. Julia Drewes of Johns Hopkins University to investigate the role of C. difficile in colorectal cancer tumorigenesis. This work was borne out of the Vanderbilt Epithelial Biology Center and its NCI-funded Colon Molecular Atlas Project (ColonMAP). Together, their work shows C. difficile is a component of pro-tumorigenic mucosal biofilms found directly overlaying human colorectal tumors. Furthermore, in genetically susceptible mouse models, toxigenic C. difficile strains accelerate tumorigenesis. Using high-dimensional, multi-omic approaches, their work provides insight into the emerging importance of the gut microbiota in colorectal cancer, and potentially early onset disease.