Profile

Timothy Rose, PhD

Timothy Rose, PhD

Infectious Disease

Children's Title: Co-Director, Center for Global Infectious Disease Research

Research Center: Center for Global Infectious Disease Research

Timothy Rose, PhD: Professor of Pediatric Infectious Diseases. The Rose Lab focuses on the role of the Kaposis sarcoma-associated herpes virus and related simian viruses in the etiology of Kaposi's sarcoma (KS) and other AIDS-related malignancies.

Current projects include the identification and characterization of cellular receptors mediating viral infection, the comparative analysis of KSHV and its simian homologs and their role in tumor induction in association with HIV-induced immunosuppression, the characterization of latency and the activating switch to herpesvirus replication, and the development of diagnostic tests for novel viruses.

Making A Difference

  • Taking Aim at a Global Health Threat

    Seattle Children’s lands a major NIH grant to take a multi-pronged look at how the virus that causes Kaposi’s sarcoma spreads and turns cancerous. ... cont.

  • Improving Virus Detection

    Tim Rose, PhD, and his colleagues are developing sensitive virus assays that have broad specificity and are fast, portable and inexpensive. ... cont.

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.

Lab URL

http://www.seattlechildrens.org/research/global-infectious-disease-research/rose-lab/

Research Focus Area

Infectious Disease

Awards and Honors

Award Name Award Description Awarded By Award Date
Outstanding Mentor School of Public Health and Community Medicine 2007
K02 Independent Scientist Award National Institutes of Health 2001 - 2006
Outstanding Teacher School of Public Health and Community Medicine 1998
Shannon Award National Institutes of Health 1996

Publications

  • Timothy Rose, PhD
    KSHV attachment and entry are dependent on V3 integrin localized to specific cell surface microdomains and do not correlate with the presence of heparan sulfate. http://authors.elsevier.com/a/1PPsQ9j6wD35N
    Virology , 2014 July 24 : 464-465118-133
  • Garrigues HJ, Rubinchikova YE, Rose TM
    KSHV cell attachment sites revealed by ultra sensitive tyramide signal amplification (TSA) localize to membrane microdomains that are up-regulated on mitotic cells.
    Virology , 2014 Mar. : 452-45375-85
  • DeMaster LK, Rose TM
    A critical Sp1 element in the rhesus rhadinovirus (RRV) Rta promoter confers high-level activity that correlates with cellular permissivity for viral replication.
    Virology , 2014 Jan. 5 : 448196-209
  • Bruce AG, Ryan JT, Thomas MJ, Peng X, Grundhoff A, Tsai CC, Rose TM
    Next-Generation Sequence Analysis of the Genome of RFHVMn, the Macaque Homolog of Kaposi's Sarcoma (KS)-Associated Herpesvirus, from a KS-Like Tumor of a Pig-Tailed Macaque.
    Journal of virology , 2013 Dec. : 87(24)13676-93
  • Dury AY, El Fatimy R, Tremblay S, Rose TM, Côté J, De Koninck P, Khandjian EW
    Nuclear Fragile X Mental Retardation Protein Is localized to Cajal Bodies.
    PLoS genetics , 2013 Oct. : 9(10)e1003890
  • Ryan JT, Rose TM
    Development of whole-virus multiplex luminex-based serological assays for diagnosis of infections with kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 homologs in macaques.
    Clinical and vaccine immunology : CVI , 2013 Mar. : 20(3)409-19
  • Bruce AG, Bielefeldt-Ohmann H, Barcy S, Bakke AM, Lewis P, Tsai CC, Murnane RD, Rose TM
    Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.
    PLoS pathogens , 2012 : 8(10)e1002962
  • Cherezova L, Burnside KL, Rose TM
    Conservation of complex nuclear localization signals utilizing classical and non-classical nuclear import pathways in LANA homologs of KSHV and RFHV.
    PloS one , 2011 Apr, : 6(4)e18920
  • Gessain A, Rose TM, Lavergne A, Lacoste V
    Comment on Mugisha et al. J Med Primatol 2010; 39: 71-76.
    Journal of medical primatology , 2010 Apr,
  • Timothy Rose, PhD
    iCODEHOP: Interactive Consensus Degenerate Hybrid Oligonucleotide Primers
    http://dbmi-icode-01.dbmi.pitt.edu/i-codehop-context/ , 2010
  • Bruce AG, Bakke AM, Gravett CA, DeMaster LK, Bielefeldt-Ohmann H, Burnside KL, Rose TM
    The ORF59 DNA polymerase processivity factor homologs of Old World primate RV2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques.
    Virology journal , 2009 Nov. : 205
  • Staheli JP, Ryan JT, Bruce AG, Boyce R, Rose TM
    Consensus-degenerate hybrid oligonucleotide primers (CODEHOPs) for the detection of novel viruses in non-human primates.
    Methods (San Diego, Calif.) , 2009 Sept. : 32-41
  • Boyce R, Chilana P, Rose TM
    iCODEHOP: a new interactive program for designing COnsensus-DEgenerate Hybrid Oligonucleotide Primers from multiply aligned protein sequences.
    Nucleic acids research , 2009 July : W222-8
  • Yilmaz O, Yao L, Maeda K, Rose TM, Lewis EL, Duman M, Lamont RJ, Ojcius DM
    ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis.
    Cellular microbiology , 2008 Apr, : 863-75
  • Garrigues HJ, Rubinchikova YE, Dipersio CM, Rose TM
    Integrin alphaVbeta3 Binds to the RGD motif of glycoprotein B of Kaposi's sarcoma-associated herpesvirus and functions as an RGD-dependent entry receptor.
    Journal of virology , 2008 Feb. : 1570-80
  • Bruce AG, Bakke AM, Bielefeldt-Ohmann H, Ryan JT, Thouless ME, Tsai CC, Rose TM
    High levels of retroperitoneal fibromatosis (RF)-associated herpesvirus in RF lesions in macaques are associated with ORF73 LANA expression in spindleoid tumour cells.
    The Journal of general virology , 2006 Dec. : 3529-38
  • Burnside KL, Ryan JT, Bielefeldt-Ohmann H, Gregory Bruce A, Thouless ME, Tsai CC, Rose TM
    RFHVMn ORF73 is structurally related to the KSHV ORF73 latency-associated nuclear antigen (LANA) and is expressed in retroperitoneal fibromatosis (RF) tumor cells.
    Virology , 2006 Oct. : 103-15
  • Philipp-Staheli J, Marquardt T, Thouless ME, Bruce AG, Grant RF, Tsai CC, Rose TM
    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.
    Virology journal , 2006 Mar. : 11
  • Burton M, Rose TM, Faergeman NJ, Knudsen J
    Evolution of the acyl-CoA binding protein (ACBP).
    The Biochemical journal , 2005 Dec. : 299-307
  • Rose TM
    CODEHOP-mediated PCR - a powerful technique for the identification and characterization of viral genomes.
    Virology journal , 2005 Mar. : 20
  • Bruce AG, Bakke AM, Thouless ME, Rose TM
    Development of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons.
    Virology journal , 2005 Jan. : 2
  • Rose TM, Henikoff JG, Henikoff S
    CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design.
    Nucleic acids research , 2003 July : 3763-6
  • Timothy Rose, PhD
    Seqhelp and Web interface: A tool for assisting molecular sequence analysis.
    https://bir2.biology.washington.edu/seqhelp/seqhelpinput.html , 1999
  • Timothy Rose, PhD
    Clustal W multiple alignment interface
    https://bir2.biology.washington.edu/clustalw/clustalw_form.html , 1999
  • Timothy Rose, PhD
    Invert DNA sequence
    http://bir.biology.washington.edu/Invert/invert1.html , 1999
  • Timothy Rose, PhD
    Amino acid structure and letter code learning tool
    http://bir.biology.washington.edu/AminoAcidQuiz/AAQuiz.html , 1999
  • Timothy Rose, PhD
    CODEHOP: Consensus-Degenerate Hybrid Oligonucleotide Primers PCR primers designed from multiple protein sequence alignments
    http://www.blocks.fhcrc.org/blocks/codehop.html , 1998
  • Timothy Rose, PhD
    File Converter
    http://bir.biology.washington.edu/GPConverter/converter.html , 1998
  • Timothy Rose, PhD
    Restriction site analysis
    http://bir.biology.washington.edu/Restrict/restrict.html , 1997
  • Timothy Rose, PhD
    Various patents created

Presentations

Presentations Title Event Location Date
"Kaposis sarcoma-associated herpesvirus (KSHV) and homologs in non-human primates" Uganda Research in Progress Meetings Fred Hutchinson Cancer Research Center, Vaccine Infectious Disease Division April 4, 2012
"Simian AIDS-related lymphomas are associated with a gammaherpesvirus belonging to either the lymphocryptovirus or rhadinovirus genus" 14th International Workshop on Kaposis sarcoma associated herpesvirus (KSHV) and related agents Helsinki, Finland Aug. 12, 2011
"Herpesvirus activation in SIV vaccine studies" Infectious Disease Science Program Fred Hutchinson Cancer Research Center Vaccine Infectious Disease Division Nov. 4, 2010
"The pig-tailed macaque rhadinovirus is associated with T-cell lymphomas in its natural host" International Workshop for KSHV/HHV8 and Related Agents Los Angeles, CA Sept. 1, 2010
"Correlating in vitro and in vivo data identifying novel life cycle stages of Kaposi's sarcoma-associated herpesvirus and related macaque viruses in different cell types" Center for Systems and Translational Research on Infectious Diseases University of WA May 13, 2010
"Infectious etiology of AIDS-related malignancies" Infectious Disease Senior Faculty Seminar University of Washington Nov. 9, 2009
"The search for HHV9, the member of the rhadinovirus-2 (RV2) lineage of Old World primate rhadinoviruses predicted to infect humans" 11th International Workshop for KSHV/HHV8 and Related Agents Charleston, South Carolina Sept. 14, 2009
"AIDS-related malignancies, etiological herpesviruses and the oral environment" Cross-Disciplinary Dental Science Seminar, Oral Biology 575 University of Washington May 11, 2009
"Kaposis sarcoma associated herpesvirus and homologs in macaques" Veterinarian Grand Rounds, Washington National Primate Research Center University of Washington Jan. 23, 2009

Research Funding

Grant Title Grantor Amount Award Date
Point-of-care diagnosis and surveillance of known and emerging influenza viruses - R01 AI111303 NIH/NIAID $855,731 annual directs March 15, 2014 - Feb. 28, 2019
Oral pathogenesis and host interactions of KSHV infection - P01 DE021954 NIH/NIDCR $993,231 + $120,000 annual directs June 7, 2011 - April 30, 2016
POC molecular method for detection of known and emerging respiratory viruses NIH/NIDCR $300,885.00 July 1, 2009
Viral and cellular factors involved in KSHV entry in cells of the oral mucosa NIH/NIDCR $1,125,000.00 Aug. 15, 2007
Herpesvirus latency and reactivation in macaque models of human disease NIH/NCRR $1,680,995.00 July 1, 2007