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Nicholas Markham, M.D., Ph.D.

  • Assistant Professor

Email

nick.markham@vumc.org
2213 Garland Ave (Langford)
10415-F MRBIV
Nashville, TN 37332

Nicholas Markham, M.D., Ph.D.

  • Assistant Professor

nick.markham@vumc.org

2213 Garland Ave (Langford)
10415-F MRBIV
Nashville, TN 37332

Profile

I am an Assistant Professor of Medicine in the Division of Gastroenterology at Vanderbilt University Medical Center, and I am grateful to be considered for an associate membership to the Vanderbilt-Ingram Cancer Center. My laboratory focuses on understanding interactions between the gut microbiome and colorectal cancer. As a Vanderbilt-trained gastroenterologist and cancer biologist, I have a broad scientific background and a firm commitment to developing this area of study for the benefit of patients. In graduate school, I used colorectal cancer as a model for studying cytoskeletal regulation through signaling by adhesion receptors and p120-catenin, a master regulator of adherens junctions. I continued investigating cytoskeletal dynamics during my postdoctoral fellowship co-mentored by Dr. Robert Coffey and Dr. Borden Lacy. My focus was on C. difficile infection because the toxins from this bacterium are glucoslytransferases that inhibit cytoskeletal maintenance. One project was investigating how the C. difficile toxins affect colonic stem cell growth factor signaling pathways during human infection. My preliminary data implicate the ErbB family of receptor tyrosine kinases as mediators of toxin-induced cell death. I developed the hypothesis that C. difficile toxin B (TcdB) elicits ErbB receptor phosphorylation and pathway activation to damage colonic stem and progenitor cells. I have established techniques for in vivo intrarectal instillation of purified recombinant TcdB and human colonoid culture to quantify ErbB signaling in the context of C. difficile infection. This work is currently funded by a Career Development Award from the Department of Veterans Affairs.

Drawing from my research background in C. difficile and colorectal cancer, I developed the hypothesis that prolonged exposure to C. difficile and subsequent colitis increases the risk of colon cancer formation. The relationship between C. difficile toxins, ErbB receptor tyrosine kinases, and colorectal cancer is an ongoing focus in our lab. I established a collaboration with Drs. Cindy Sears and Julia Drewes who study the disrupted spatial organization of the gut microbiota, known as invasive biofilm formation. Together, we have recently published data demonstrating how C. difficile isolated from human colorectal cancer accelerates tumorigenesis in genetically susceptible mice. My single-cell RNA-sequencing (scRNA-seq) analysis of mouse colonic tissue for that work led me to explore the integration of spatial transcriptomics and multiplex imaging. As a member of the NCI Human Tumor Atlas Network, I have applied this multi-omic approach with additional collaborations through a Trans-Network Project including Vanderbilt, Johns Hopkins, Stanford, and Washington University. This team is creating an atlas of human colorectal cancer. Ours is unique among the HTAN projects because of our specific attention to intra-tumor bacteria as a component of the tumor microenvironment. Together, the components of my research program and my clinical experience have coalesced into my passion for studying colorectal cancer and new opportunities to diagnosis and treat it.

Education

  • M.D., Vanderbilt University, Nashville, Tennessee (2014)
  • Ph.D., Vanderbilt University, Nashville, Tennessee (2012)
  • B.A., Colby College, Waterville, Maine (2004)
Postdoctoral Training
  • Fellowship, Vanderbilt University Medical Center (2020)

Research Emphasis

Research Description

Publications

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