Cell state transitions underlie cancer progression and the response to chemo- or molecularly-targeted therapy. As cancer cells evolve toward their most aggressive forms, their cellular differentiation status generally degrades, becoming more developmentally primitive. We have uncovered multiple roles for specific tumors suppressor genes that unlock cell state plasticity when inactivated. Understanding the molecular constraints on cell state transitions has the potential to identify strategies that can limit cell state transition as a mechanism of resistance and increase the durability of targeted therapies.

In this space, we use novel genetically engineered animal and tumor spheroid models to identify relevant cell state transitions and link these changes with alterations in the genetic and epigenetic landscape. Contact David to learn more about joining this team.