Laboratory of Growth Control and Cancer Research

Growth is fundamental to development, yet remarkably little is known about the mechanisms that control organ size. How do cells know when to stop dividing after an organ has reached its proper size, and how do injured organs regenerate damaged or missing parts? We are using the fruit fly Drosophila as a genetic model system and vertebrate cell culture systems to address these questions and to discover signaling pathways that regulate growth, regeneration and the development of cancer. We translate the knowledge gained in Drosophila to vertebrate systems where we address questions of growth control and cancer in cell culture systems that mimic in vivo situations, such as two- and three-dimensional hydrogel cultures. The combination of the powerful genetic tools available in Drosophila with novel and complex mammalian experimental cellular systems provides a superb platform in which to discover and study the signaling mechanisms governing organ growth control, regeneration and cancer cell evolution. Through genome-wide genetic screens in Drosophila we discovered a novel growth control pathway, the “Hippo pathway”. Animals carrying mutations in hippo develop severely overgrown structures and have tumorous overgrowths. Strikingly, the Hippo pathway is highly conserved in vertebrates where it also regulates growth and is often mutant in cancer. We are currently using several genetic screening strategies such as a genome-wide transgenic RNAi library and chemical mutagenesis to screen for upstream regulator of the Hippo pathway.

We currently focus on three main topics:

1) How mechanical forces regulate cellular behavior and the Hippo pathway.

2) The regulation of cell competition and the role of the Hippo pathway therein.

3) The role of the Hippo pathway in cancer cell dormancy. These three projects are highly related and interconnected and aim at understanding the extracellular signals that regulate the Hippo pathway and how Hippo signaling and other pathways are normally involved in growth control and regeneration and how misregulation of the Hippo pathway leads to cancer.