Leonard B. Maggi, Jr., Ph.D.

Cancers arise from a cell’s inability to control not only proliferation (increase in cell number) but also growth (macromolecular synthesis). Increasing proliferation without a coinciding increase in cell growth would result in smaller and smaller daughter cells. The nucleolus, a subnuclear organelle, is the production site of the cell’s protein synthesis machinery, the ribosome. Historically thought of as a static subnuclear organelle, the nucleolus has recently been shown to be a dynamically important part of the cell governing growth. In addition to producing ribosomes, the nucleolus also houses several oncogenes and tumor suppressors which monitor pro-growth signals from the cell. We have shown one nucleolar oncogene, nucleophosmin, regulates ribosome biogenesis and its overexpression can transform immortalized cells. The nucleolar tumor suppressor, p19ARF (p14 in humans) regulates nucleolar function at multiple steps from rRNA transcription to export of ribosomal subunits. Mutations in nucleolar proteins as well as the pathways that signal to them can result in tumorigenesis. We are interested in understanding the regulation of nucleolar function and how alterations in nucleolar protein function can lead to tumorigenesis.