Molecular biology of RNA picornaviruses; protein translation, proteolytic processing; RNA replication; viral pathogenesis; viral vaccines; bioinformatics; comparative proteomics, sequence analysis; computer-assisted RNA structure determinations.
We are interested in all aspects of RNA virology and in bioinformatics methods for viral genomics. Previous focus in the lab centered the relationship of the cardiovirus genus to other members of the picornavirus family and the unique features of the cardioviruses. We used this system to examine molecular questions about picornavirus translation, proteolytic processing, morphogenesis and pathogenicity. More recently, those learned techniques have been applied to the related species of human rhinoviruses, with particular attention to the recently discovered RV-C species. We have developed powerful experimental systems for examining viral protein expression, RNA synthesis, virion assembly and virus-host interactions. We use high-tec recombinant engineering, structural biology, reverse genetics, biochemistry, cell-free protein synthesis techniques, cell imaging and applied immunology to unravel the virus life cycle, step by step. Current projects include: 1) investigation of the CDHR3 cellular receptor for RV-C and its potential as an antiviral target; 2) datamining of collective RV genome sequences so this new species can be placed into evolutionary perspective; 3) investigation of the the nuclear life cycle of cytoplasmic viruses; 4) role of viral proteins, particularly protease 2A in the disruption of nucleocytoplasmic protein and RNA cycling; 5) development and implementation of new techniques in bioinformatics, sequence analysis, comparative genome evolution, and advanced computer methods for RNA folding and molecular genomics.
Additionally, many of our genetically engineered viruses have proven to be superb attenuated vaccines or vaccine vectors, in that they provide effective, long-lived anti-picornavirus immunity in many species of mammals, including primates. We are exploiting these constructions for the prevention of picornavirus diseases, but have also harnessed these agents into novel, recombinant vaccine vectors.