Picornaviruses are small, non-enveloped viruses with a positive-sense RNA genome.  My current research is the biochemistry of how these viruses are replicated in infected mammalian cells and how certain cellular biochemical processes participate in viral replication cycles.  I am particularly interested in the biochemistry of encephalomyocarditis virus (EMCV) and hepatitis A virus (HAV) replication.  Much of my research is focused upon understanding how viral protein concentrations are regulated during replication and the role that viral polyprotein processing proteases play in facilitating the successful production of progeny virions. 

The concentration of each protein in a cell is a function of the rate at which it is produced and the rate at which it is degraded.  This applies to viral proteins in infected cells.  In the case of picornaviruses, the rate of mature viral protein production is determined by the rates of new RNA synthesis, translation of the positive-strand RNA, and proteolytic processing of the viral polyprotein precursor encoded by the RNA.  While part of my research includes studies of picornaviral RNA synthesis and translation rates, most of my efforts are focused upon understanding how picornaviral protein concentrations are regulated by polyprotein processing and viral protein degradation.   Most of the viral polyprotein processing steps are catalyzed by the 3C proteases, encoded within the genomes of picornaviruses.   My students and I are examining the kinetics of EMCV and HAV 3C protease activity with the goal of better understanding how these proteases select peptide bond cleavage sites in substrate proteins.  Besides helping us to understand how 3C protease-dependent cleavage reactions help regulate viral protein concentrations, this research may improve our ability to identify cellular 3C protease substrates that are cleaved during the infection cycle.   Certain EMCV and HAV proteins and polyprotein precursors, including the 3C proteases, are subjected to rapid and selective degradation by the mammalian ubiquitin/26S proteasome system.  The biochemistry of this system, particularly how it targets picornaviral proteins for ubiquitin attachment, has been an important part of the work in my laboratory for the past several years.   More recently, we have begun to examine other roles of the proteasome in the establishment of a productive EMCV replication process in infected cells.

One of my most important goals is to use my research program to provide education and research training opportunities for potential beginning scientists.  I welcome the participation of highly motivated undergraduates who are serious about wanting to be part of an exciting research endeavor, especially those students who are considering post-graduate careers as practicing scientists.   More than 60 undergraduates and several high school students have worked with me in my laboratory since it was established at Bates in 1989.  My research has been funded by the National Science Foundation, the National Institutes of Health, Research Corporation, The Camille and Henry Dreyfus Foundation, and the Howard Hughes Medical Institute.