DiMaio Lab Research
Our research focuses on the papillomaviruses and polyomaviruses, small DNA viruses that transform cells in culture and play an important role in several forms of human cancer and other diseases. Our current studies aim to determine at the molecular level how viral oncogenes transform cells and cause cancer and how these viruses use cellular machinery to enter cells.
- The laboratory is studying the mechanism of action of the smallest known naturally occurring oncoprotein, the 44-amino acid E5 protein expressed by bovine papillomavirus. We showed that the BPV E5 protein binds and activates the PDGF receptor tyrosine kinase in a ligand-independent manner. Further studies of this interaction will provide new insight into signal transduction, protein-protein interactions, and the control of cell proliferation.
Artificial Small Transmembrane Proteins as Novel Agents to Modulate Cell Behavior and Study Protein-protein InteractionsBased on our analysis of the BPV E5 protein, we devised a genetic approach to construct and identify small transmembrane proteins that can alter cell behavior. We have isolated artificial proteins that can transform cells to tumorigenicity, induce red blood cell formation, or confer resistance to HIV infection. We have also isolated the simplest expressed proteins ever described.
- Entry of tumor viruses into cells is the first step in viral-mediated tumorigenesis. Virus entry is a complex, multi-step process that requires numerous cellular proteins. We are using genetic and cell biological approaches to identify and characterize cellular proteins required for successful infection by small DNA tumor viruses.
- The laboratory is investigating the role of the human papillomavirus E6 and E7 proteins in cervical cancer and oropharyngeal cancer, with particular attention to their ability to inhibit cellular senescence. We are also studying the influence of cell growth state on cellular microRNA biosynthesis and function.