Cell-cell communication must be achieved with high fidelity to avoid catastrophes such as cancer. Our goal is to understand the detailed biochemical principles of cell-cell signaling, with an emphasis on how these biochemical reactions are organized in the spatial and temporal dimension. A major emphasis is on developmental signaling pathways orchestrated at the primary cilium, an antenna-like projection that functions as an important signaling center in both development and human disease.
The primary cilium is a dramatic example of spatial organization in the cell. Composed of more than a thousand proteins, this elaborate structure projects from the surface of most mammalian cells. Often only a few microns long, cilia are marvelously complex machines that play a central role in the efficient detection and interpretation of signals from the environment. Primary cilia coordinate multiple signaling pathways important for embryogenesis, organogenesis, and sensory function. Defects in cilia lead to human pathologies ranging from congenital anomalies to cystic disease and obesity. The diversity of these phenotypes is a testament to the pervasive importance of cilia in human physiology.
We use the hedgehog signaling pathway as an accessible model to decipher fundamental principles of ciliary signal transduction. We expect that insights gained in these studies will help elucidate the function of this mysterious organelle and open the doors to the development of cilia-targeted therapeutics.
We approach scientific problems by integrating bulk methods, such as biochemical reconstitution and protein purification, with single cell methods, such as microscopy using innovative optical and chemical probes.