Heterogeneity in the Epithelial-to-Mesenchymal Transition

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William L Hwang, William Freed-Pastor, Laurens Lambert, Tyler Jacks

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Unlike conventional cell culture, organoids (“mini-organs” grown in a dish) faithfully recapitulate many architectural and physiological features of the tissue they derive from and therefore represent a powerful model system. In this pancreatic organoid engineered to carry mutations in two of the most commonly perturbed genes in pancreatic cancer (Kras and Tp53), the attached image captures the ongoing transformation of pancreatic organoid cells from a less invasive state (green) to a more invasive state (red). The goal of this project is to elucidate the subset of genetic perturbations that are sufficient to confer certain complex phenotypes in pancreatic cancer.