Cell Polarity Signaling Driving Collective Cell Behavior

About This Grant

Project Summary This research program will uncover how epithelial cells coordinate their polarity, adhesion, and signaling to generate the collective cell behaviors that build and maintain tissues. Epithelial collectives are essential for normal organ development and repair, but these same programs are frequently hijacked during cancer progression to promote invasion, resistance to mechanical stress, and metastatic dissemination. A central focus of our lab in the next five years is to understand polarity signaling through the protein, Scribble, which regulates adhesion and Rho-family GTPase activity, and whose amplification or misregulation is common in human cancers. By integrating discoveries in Drosophila border cell migration with experiments in pancreatic organoid models, this project leverages the strengths of both systems: the genetic power and single-cell resolution of Drosophila, and the physiological relevance of mammalian organoids. Border cells provide an unparalleled system for dissecting leader–follower dynamics, enabling us to define how polarity signaling stabilizes adhesion and sculpts small GTPase activity in vivo. While, pancreatic organoids extend these findings into human-relevant contexts, allowing us to test how polarity regulates lumen formation, force generation, and morphogenesis under mechanical confinement. The long-term vision is to build a unified framework of how polarity signaling generates emergent epithelial behaviors across scales, from molecules to tissues. This work will advance basic biology by defining conserved principles of collective migration, adhesion, and growth, and will provide new conceptual models for how cancer cells exploit polarity pathways to adapt to stiff, fibrotic microenvironments. The