Grant: Operating Grant

Epithelial cells are a fundamental building block of the human body and form a major component of most organs. Epithelial cells align like cobblestones to form sheets. These epithelial sheets can be shaped into a multitude of different forms during development that cover our body (the skin) or compose many organs such as the lungs, liver, pancreas, gut, blood vessels and many others. The significance of epithelial tissues to give the human and animal body its structure and to determine the physiology of many organs is reflected in the many diseases that are caused by defects in epithelial cells including approximately 80% of all human cancers. The ability of epithelial cells to form sheets is at the heart of the ability of epithelia to fulfill their divers functions. This ability of epithelial cells depends on the asymmetric structural organization of each individual cells that is referred to as apical basal polarity. Thus, each cobblestone has a front and a back end, and all front and back ends need to be aligned to form a functioning epithelial sheet. Our laboratory has investigated the genetic and molecular mechanisms that allow epithelial cells to build their apical basal polarity for over 20 years. We and many colleagues in this field have made great progress in understanding how this polarity comes about. However, many gaps in our understanding of this fundamental aspect of all animal life remain. We have recently made an exciting discovery that links two of the cellular machineries that are at the core of epithelial polarity. This applications request funding to fully explore this link, which will deepen our understanding of epithelial polarity, and therefore will enhance our ability to identify biomakers or therapeutic targets for diseases that are caused by defects in epithelial cell architecture.