Automated detection and quantitation of gastric immune cells in a mouse model of H. pylori-driven preneoplastic progression21 OCTOBER 2021
8:00 AM – 9:00 AM PDT | 11:00 AM – 12:00 PM EDT | 4:00 PM – 5:00 PM BST
This webinar is ideal for infectious disease researchers, pathologists, attending physicians, image analysts, and others working in digital pathology.
Gastric cancer is the fourth-leading cause of cancer death worldwide. About 80% of cases are attributable to infection with the bacterium Helicobacter pylori (Hp). Untreated Hp infection causes lifelong stomach inflammation that does not eradicate the bacterium. In some individuals, stomach inflammation leads to preneoplastic progression, a series of sequential tissue changes including loss of gastric acid-producing parietal cells, metaplasia, dysplasia, and finally cancer. Whether and how Hp infection and associated inflammation can promote each stage of disease development is not well understood. In a mouse model, induction of a constitutively active Kras allele in the stomach recapitulates the same gastric preneoplastic progression seen in humans (loss of parietal cells followed by development of metaplasia and dysplasia). Sustained Hp infection plus active KRAS expression (Hp+KRAS+) led to greater immunopathology, altered T cell and macrophage polarization, increased cell proliferation, altered metaplasia marker expression, and accelerated dysplasia, compared to Hp-KRAS+ mice. These findings suggest that gastric inflammation and disease progression may differ between Hp+ vs. Hp– cases, which could have important therapeutic implications in humans.
Valerie O’Brien, PhD
Post-Doctoral Research Fellow
Fred Hutchinson Cancer Research Center
Valerie O’Brien received her Ph.D. in Molecular Microbiology and Microbial Pathogenesis from Washington University in St. Louis. She is currently investigating gastric cancer as a post-doctoral research fellow in the Salama lab at Fred Hutchinson Cancer Research Center. The vast majority of gastric cancers are attributable to stomach infection with the bacterium Helicobacter pylori(Hp), which elicits chronic inflammation that drives gastric pathology. However, the mechanism(s) through which chronic Hpinfection and associated inflammation lead to gastric cancer are not well understood. Dr. O’Brien’s work integrates a novel mouse model of gastric preneoplastic progression, bacterial genetics and studies of human samples to investigate mechanisms of Hp-driven inflammation and disease.
Paul Kong
Research Technologist
Fred Hutchinson Cancer Research Center
Paul has over 15 years of experience in anatomical pathology with an emphasis on immunohistochemistry, including stints at PhenoPath Laboratories as a research technologist and CRO lab supervisor and at Leica Biosystems as a Field Applications Specialist. Currently, he is a research technologist at Fred Hutchinson Cancer Research Center specializing in multiplex immunohistochemistry panel development, digital pathology, and Halo image analysis.
