The goal of this project is to define the downstream elements of polycystin signaling. We have defined a cilia dependent cyst activating (CDCA) phenotype downstream of loss of polycystins from epithelial cells with intact cilia. We are systematically identifying the molecular components and defining the respective mechanisms of action of the CDCA pathway.
Welcome to the Somlo lab
Research Objectives
- Our laboratory applies molecular genetic approaches to define the mechanisms underlying autosomal dominant polycystic kidney and liver diseases (ADPKD).
- Specifically, we seek to discover the signaling pathways controlled by polycystin-1 (Pkd1), polycystin-2 (Pkd2) and primary cilia that are responsible for the establishment and maintenance of the structure and function of the metanephric kidney and of bile ducts in the liver.
Projects
Molecular Modulators of Polycystin Signaling Polycystin Dependent Mechanisms of Tubular Plasticity We have used genetic engineering in mouse models to show that polycystic kidney disease can be reversed by re-expression of the respective Pkd gene. This reversibility has defined a remarkable plasticity in the adult mammalian kidney. We are now investigating the molecular pathways by which polycystin re-expression can revert polycystic kidneys to the noncystic state.
Structural Determinants of Polycystin Function We have established and extensive array of tools with which we are studying the disruption of normal polycystin function by pathogenic mutations.