Timothy Rose, PhD

Overview

Research Description

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.

Research Focus Area

Infectious Disease

Publications

Presentations

Research Funding