Feb. 6 Seminar: Jose Onuchic, Rice University – Can Theory Help Cancer Biology?
4:00 – 5:00 pm – Pancoe Auditorium – Monday, Feb. 6
José Nelson Onuchic
Center for Theoretical Biological Physics and Departments of Physics and Astronomy, Chemistry, and Biosciences
Rice University, Houston, Texas
The Genetics and Biophysics of Epithelial-Mesenchymal Transition (EMT): Can Theory Help Cancer Biology?
Understanding epithelial-mesenchymal transitions during cancer metastasis remains a major challenge in modern biology. Thanks to the rapidly growing body of cell behavior observations and progress in mapping the key regulatory genetic networks associated with these decisions, it is now confirmed that the genetic network that regulates the epithelial-mesenchymal transitions is also able to create an epithelial-mesenchymal hybrid phenotype (E/M). These hybrid cells possess mixed epithelial and mesenchymal characteristics, enabling specialized capabilities such as collective cell migration. On the gene network level, it is now understood that the coexistence of and transitions between the different phenotypes are regulated by a decision unit composed of two highly interconnected chimeric modules: the miR-34/SNAI and the miR-200/ZEB mutual inhibition feedback circuits. A new tractable theoretical framework to model and decode the operating principles governing these decision units will be presented. This approach connects between the knowledge about intracellular pathways and observations of cellular behavior, and advances towards understanding the logic of cancer decision making. Finally we devise a mechanism-based theoretical model that links cell–cell communication via Notch-Delta-Jagged signaling with the regulation of EMT. We demonstrate that while both Notch-Delta and Notch-Jagged signaling can induce EMT in a population of cells, only Jagged-dominated Notch signaling, but not Delta-dominated signaling, can lead to the formation of clusters containing hybrid E/M cells.