Our research focuses on two aspects of human disease. First, we are interested in understanding the role phenotypic switching plays in yeast infections. In 1987, the white-opaque transition was identified in a strain of Candida albicans isolated in a blood stream infection. Recently, it was discovered that this phenotypic transition is an essential step in C. albicans mating, and unique signaling occurs between opaque and white cells. Opaque cells signal white cells to form a tissue (a biofilm), that facilitates mating between opaque cells. We are actively elucidating the molecular mechanisms that regulate this transition. Second, we are interested in the defects in motility and chemotaxis resulting in human disease. Using a combination of computer-assisted motion analysis techniques, fluorescence microscopy, and molecular genetic techniques, we are analyzing the interactions between the myosins, actin and the tumor suppressor PTEN in the cortical regulation of lateral pseudopod formation in the model system Dictyostelium discoideum. We are also interested in the role of calcium in motility and chemotaxis. We have begun to apply our findings to two human diseases, the Schwachman-Diamond Syndrome and the major genetic disease in man, polycystic kidney disease. We have recently identified a motility defect in the former and chemotaxis defects in the latter. We are pursuing the functions of the genes responsible for these deadly diseases..