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Research Interests
Our research is focused on herpesviruses implicated in cellular
transformation and tumor induction, and in the study of host and viral
proteins and cytokines which mediate these effects. In particular, we are
studying the viral etiology of Kaposi's sarcoma (KS) and other AIDS-related
malignancies with regards to the interactions between viruses (retroviruses
and herpesviruses) and cytokines in virus activation and tumor induction. We
have discovered and are characterizing a new herpesvirus, retroperitoneal
fibromatosis herpesvirus (RFHV), which is a homolog of Kaposi's
sarcoma-associated herpesvirus (KSHV) in two macaque species (Rose
et al., 1997; Schultz
et al., 2000;). The macaque viruses are
associated with a Kaposi's sarcoma-like malignancy, called retroperitoneal
fibromatosis (RF) (Bruce et al.,
2006), which like AIDS-KS is associated with a retrovirus infection. RF occurs in conjunction with simian AIDS
(SAIDS) caused by infection with simian retrovirus 2 (SRV2) or the simian
homolog of HIV, SIV (Bielefeldt-Ohmann
et al., 2005). We have identified
a second lineage of KSHV-like rhadinoviruses in macaques and are studying its
role in RF and other macaque tumors (Schultz
et al., 2000; Bruce et
al., 2005). We have recently
identified the strain of SRV2 associated with SAIDS-RF in the Washington National Primate Research
Center (Staheli et al., 2006) and
are studying its role in rhadinovirus activation and tumor induction. Ongoing projects include the cloning and
sequence analysis of the genome of the new macaque herpesvirus (Rose
et al., 2003), the search for transformation- and latency-related genes (Burnside
et al., 2006) and cytokine inducing genes in these viruses, and the
development of the macaque system as an animal model for studying KS in
humans. We also identified a cellular entry
receptor for KSHV and are studying virus-cell interactions through the virion
glycoprotein B using confocal microscopy and cellular biology approaches,
(Garrigues et al., 2008). We
developed a novel technique using consensus-degenerate hybrid oligonucleotide
primers (CODEHOP) for the identification of distantly related genes (Rose
et al., 1998; Rose et al.,
2003), and have used this technique to discover the macaque herpesviruses
described above, as well as to identify other novel retroviruses (Wilson
et al., 1998; Osterhaus
et al., 1999) and herpesviruses (Rose,
2005). We have developed an
interactive software program and web site for the design of CODEHOP PCR
primers for the identification of distantly related genes (iCODEHOP). We
are working closely with the Washington
National Primate Research Center
to identify new pathogens infecting primates maintained at the Center, and are
developing CODEHOP PCR assays to detect novel primate virus species. Finally, we have a strong interest in
bioinformatics and have developed a "Biological
Information Resource" for students and researchers at the University of Washington. For this resource, sequence analysis
software has been developed and DNA and protein databases are maintained for
bioinformatics research. We offer a
graduate level course in “Bioinformatics and Gene
Sequence Analysis” (PABIO/MEBI/PHG 536) for students wishing to
further their knowledge and expertise in this field. Our research approaches include virology,
using both in vitro and in vivo models, cellular biology, studying signaling
and protein interactions, protein chemistry, studying functions of
recombinantly expressed proteins and protein mutations, microscopy, using a
dedicated confocal microscope, molecular biology, for viral pathogen
identification and characterization and bioinformatics, for viral gene and
genome analysis.
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