Role of the Tumor Micro-Environment in Cancer Development
Cervical cancer, a leading cause of cancer death in women worldwide, is controlled in developed countries through population-wide screening that offers unique opportunities to study cancer development. Cervical cancer is caused by human papillomavirus, in combination with additional genetic changes acquired during the long progression of papillomavirus-positive precancerous lesions into fully malignant tumors. Our recent studies reveal that the development and continuing survival of cervical cancers also depend on interactions between the tumor cells and surrounding noncancerous cells. Among other functions, these surrounding noncancerous, or stromal, cells appear to provide signals required for continuing tumor cell proliferation. Ongoing studies are using a range of imaging, gene expression, and computational approaches to determine the specific types of stromal cells involved, the nature of the molecular signals exchanged in both directions between tumor and stromal cells, and the consequences for tumor cell growth and invasiveness. The results have implications for prevention and diagnosis of and therapy for these and other cancers.
Novel Mini-Organelles for RNA Virus Genome Replication
Cells have DNA genomes, but most viruses store, replicate, and evolve their genes as RNA, with no natural DNA forms. We are studying this unique RNA-based lifestyle to better understand, prevent, and treat virus infections. We find that viruses replicate their RNA genomes by first dramatically rearranging cell membranes to create new mini-organelles that organize the factors and steps of RNA replication and protect them from host defense responses. Our recent studies of the underlying molecular mechanisms have revealed striking new features of these fascinating RNA replication machines as well as surprising roles of viral and cellular genes in their formation and function. This project combines molecular genetics, biochemistry, and advanced light and electron microscopy imaging to study the protein, RNA, and membrane interactions involved in these processes. Ongoing results are illuminating many new aspects of viral and cell biology, including functional and likely evolutionary links uniting multiple classes of viruses.