Undergraduate

University of California (San Diego), BA, Biology, 1972

Graduate

University of Geneva (Switzerland), PhD, Molecular Biology, 1981

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.

1. Rose TM, Henikoff JG, Henikoff S (2003). CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design. Nucleic Acids Res 31(13):3763-3766.


2. Rose TM, Ryan JT, Schultz ER, Raden BW, Tsai CC (2003). Analysis of 4.3 kilobases of divergent locus B of macaque retroperitoneal fibromatosis-associated herpesvirus reveals a close similarity in gene sequence and genome organization to Kaposi's sarcoma-associated herpesvirus. J Virol 77(9):5084-5097.


3. Bielefeldt-Ohmann H, Barouch DH, Bakke AM, Bruce AG, Durning M, Grant R, Letvin NL, Ryan JT, Schmidt A, Thouless ME, Rose TM (2005). Intestinal stromal tumors in a simian immunodeficiency virus-infected, simian retrovirus-2 negative rhesus macaque (Macaca mulatta). Vet Pathol 42(3):391-396.


4. Bruce AG, Bakke AM, Thouless ME, Rose TM (2005). Development of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons. Virol J 2:2.


5. Rose TM (2005). CODEHOP-mediated PCR - a powerful technique for the identification and characterization of viral genomes. Virol J 2:20.


6. Bruce AG, Bakke AM, Bielefeldt-Ohmann H, Ryan JT, Thouless ME, Tsai CC, Rose TM (2006). High levels of retroperitoneal fibromatosis (RF)-associated herpesvirus in RF lesions in macaques are associated with ORF73 LANA expression in spindleoid tumour cells. J Gen Virol 87(Pt 12):3529-3538.


7. Burnside KL, Ryan JT, Bielefeldt-Ohmann H, Gregory Bruce A, Thouless ME, Tsai CC, Rose TM (2006). RFHVMn ORF73 is structurally related to the KSHV ORF73 latency-associated nuclear antigen (LANA) and is expressed in retroperitoneal fibromatosis (RF) tumor cells. Virology 354(1):103-115.


8. Philipp-Staheli J, Marquardt T, Thouless ME, Bruce AG, Grant RF, Tsai CC, Rose TM (2006). Genetic variability of the envelope gene of Type D simian retrovirus-2 (SRV-2) subtypes associated with SAIDS-related retroperitoneal fibromatosis in different macaque species. Virol J 3:11. PMCID: PMC1450265.


9. Garrigues HJ, Rubinchikova YE, Dipersio CM, Rose TM (2008). Integrin alphaVbeta3 Binds to the RGD motif of glycoprotein B of Kaposi's sarcoma-associated herpesvirus and functions as an RGD-dependent entry receptor. J Virol 82(3):1570-1580. PMCID: PMC2224453.


10. Yilmaz O, Yao L, Maeda K, Rose TM, Lewis EL, Duman M, Lamont RJ, Ojcius DM (2008). ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis. Cell Microbiol 10(4):863-875. PMCID: PMC2637656.