My area of specialization is the molecular biology of papovaviruses, with a primary focus on how viral proteins modify the host cell environment. Recently, we determined that the viral replication proteins, E1 and E2, are post-translationally modified by addition of 1 or more SUMO moieties. Sumoylation is a widespread modification whose biological functions are only recently becoming understood. Studies are in progress to 1) determine the role of sumoylation in the viral life cycle, 2) evaluate the effect of sumoylation on the structure and activity of the E1 helicase, 3) understand the mechanism by which sumoylation influences E2 stability and transcriptional activity, and 4) determine how sumoylation is modulated by the viral E6 oncoprotein.   In addition to the role of sumoylation in the viral life cycle, we are also exploring how sumoylation participates in normal keratinocyte differentiation.  We have developed a keratinocyte cell line inducibly expressing a tagged SUMO moiety to facilitate proteomics studies of sumoylation changes and regulation during controlled differentiation.