Picornaviruses are prevalent human pathogens and cause diseases ranging from the common cold, to jaundice, myocarditis and paralysis. Included in this family are poliovirus, rhinovirus, hepatitis A virus, coxsackievirus, echovirus and others. My goals are to understand, at a molecular level, the host-pathogen interactions that occur during picornavirus infection. In addition to enhancing our understanding of picornavirus molecular biology and pathogenesis, my research plan is designed to provide insights into the mechanisms underlying such basic cellular processes as signal transduction, regulation of gene expression and nucleo-cytoplasmic trafficking. To achieve these goals I utilize a multidisciplinary approach that incorporates cell biology, molecular biology, genetics, biochemistry and functional genomics.

During poliovirus and rhinovirus infection a number of host nuclear proteins relocalize from the nucleus to the cytoplasm. Recently, we demonstrated that both poliovirus and rhinovirus infection cause a dramatic inhibition of nuclear import coincident with the cytoplasmic accumulation of host nuclear proteins. We have also shown that two components of the nuclear pore complex (NPC), Nup153 and p62, are degraded during infection, thus providing a potential mechanism to account for the observed inhibition of nuclear import. Inhibition of nuclear import is predicted to result in the cytoplasmic accumulation of a number of nuclear proteins that normally function in RNA biogenesis and transport, activities that an RNA virus replicating in the cytoplasm might find advantageous. Additionally, many anti-viral responses involve the transport of cytoplasmic signaling molecules, such as NFB and STATs into the nucleus. Inhibition of nuclear import may thus provide an attenuated anti-viral response and lead to a more productive replicative cycle in vivo.

Currently, the major focus of the lab is to determine the role that inhibition of nucleo-cytoplasmic trafficking plays in viral replication and pathogenesis and the impact of this inhibition on the host cell. A major effort is underway to identify the viral factors responsible for the inhibition of nuclear import and degradation of NPC components that occurs during poliovirus and rhinovirus infection. To better understand the consequences of viral infection on nucleo-cytoplasmic trafficking and NPC composition, a second project focuses on characterizing the status of specific trafficking pathways and NPC components in infected cells. Yet another project is aimed at determining if picornaviruses attenuate the host anti-viral response by examining the ability of infected cells to mediate signal transduction from the cytoplasm to the nucleus. If you think you would be interested in working in the lab on one of these diverse projects please feel free to drop by my office or contact me by phone or email.