Grant: Operating Grant

The centrosome is the major microtubule-organizing center of animal cells. It is best known for its role in cell division (in forming the mitotic spindle) and in templating the formation of cell cilia critical for proliferation, differentiation, and development. Centrosome aberrations are implicated in a wide variety of diseases including cancer, and supernumerary centrosomes are a distinguishing feature of many cancer cells. In addition, ciliary defects can also mediate tumorigenesis and induce ciliary disorders such as polycystic kidney disease. Although centrosomes were identified over a hundred years ago, their molecular structure and composition are not fully understood, and the functions of many individual centrosomal components remain elusive. Our research focuses on one novel centrosomal protein, NPHP5, whose de-regulation is implicated in human ciliary disease and cancer. Through three specific aims, we will examine the function of NPHP5 at the molecular, cellular, and organismal level, and evaluate its contribution to disease. These study results will serve as an important step towards understanding the pathological mechanisms of centrosome dysfunction, and in guiding the development of novel diagnostic and therapeutic applications for diseased patients.