MEMBRANE TRAFFIC AND CELL MOTILITY
The central focus of the laboratory is the development and use of new optical microscopy and biophysical techniques to study the properties of living cells. We use digital imaging devices, confocal microscopes, multiphoton microscopy, automated microscopy systems, and image processing computers to analyze processes occurring at specific sites within cells. Using these tools, we study the distribution and movement of various types of molecules in cells. We are interested both in the basic mechanisms regulating the movement of molecules through cells as well as the role that these processes play in specific diseases. Our studies of endocytic trafficking are aimed at developing a complete map and kinetic model for endocytic membrane traffic of receptors, ligands, and membrane lipid components. We use fluorescent tracers to follow the fates of specific molecules. For example, we have used naturally fluorescent sterols to see how cholesterol moves around in cells. We also use various biochemical and molecular biology techniques to test the role of specific proteins in directing membrane traffic in living cells. We are also studying disease-related endocytic processes such as the uptake of large lipoproteins by macrophages leading to atherosclerotic lesions and the interaction of cells with the proteins that form Alzheimer's disease plaques. Each of these uses variations of the basic endocytic processes that we have characterized.