Molecular mechanisms of colorectal cancer development, with Prof. Alberto Martin PhD
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This episode features Prof. Alberto Martin from University of Toronto (Canada), speaking about the molecular mechanisms by which certain bacteria – namely, pks+ E. coli – influence colorectal cancer development. pks+ E. coli secretes a toxin that causes DNA damage; likely its purpose is to keep other microorganisms in check, but it appears to have the effect of promoting colorectal cancer. A low-fiber diet starves mucolytic bacteria, reducing the mucus layer in the gut and allowing pks+ E. coli to come into contact with the colonic epithelial cells, where they secrete the toxin that causes DNA damage. Gut inflammation also factors in, because these bacteria thrive in an inflammatory environment. Interestingly, in looking at the geographic distribution of this microorganism in people around the world, its presence correlates with colorectal cancer rates. Prof. Martin’s lab has clinical trials planned to explore this connection, and other groups are looking at therapies to reduce this microorganism in the gut.
Episode abbreviations and links:
- Paper on diet and pks+ E. coli interactions in colorectal cancer development: Dietary fibre counters the oncogenic potential of colibactin-producing Escherichia coli in colorectal cancer
- Paper showing a large proportion of bacterial isolates from IBD patients had DNA-damaging agents: Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
- Paper showing correlation of pks+ E. coli in the population and rates of cancer around the world: Geographical variation in the incidence of colorectal cancer and urinary tract cancer is associated with population exposure to colibactin-producing Escherichia coli
- Paper showing a distinct mutational signature in human cancer genomes, possibly arising from exposure to genotoxic pks+ E. coli: Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli
About Prof. Alberto Martin PhD:
Dr. Martin is a Professor and Sanofi Pasteur Chair in Human Immunology in the Department of Immunology at the University of Toronto. He completed his B.Sc. degree at McGill University, and his PhD degree in the Department of Immunology at the University of Toronto. He then pursued post-doctoral training at Albert Einstein College of Medicine in New York, U.S.A., with Dr. Matthew Scharff, focusing on characterizing the molecular mechanisms of antibody responses, specifically somatic hypermutation and class switch recombination, which are two processes that are central to the efficient neutralization of pathogens and toxins. In 2003, he was recruited as a faculty member to the Department of Immunology at the University of Toronto.
Dr. Martin’s research program is devoted to understanding the role of genes, their interaction with the environment, and their impact on immunity and pathological conditions, including cancer. His main interest is on antibody production, on how high-affinity antibodies are generated, and how antibodies of different classes are produced. Both of these processes are necessary for an efficient antibody response. Dr. Martin is also investigating the role of the gut microbiota in the etiology of colon cancer and has characterizing the role of diet in modulating the cancer causing effects of specific pathobionts. His lab is also investigating the role of a new gene and how it promotes inflammatory bowel disease (IBD). This work highlights the metabolic effects of the skeletal muscle in supporting a metabolically taxing inflammatory process such as IBD.
