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.

About My Work

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

  • Hirata A | Hashimoto K | Katoh Y | Sakai H | Bruce AG | Rose TM | Kaneko A | Suzuki J | Nikami H | Yanai T
    Characterization of spontaneous malignant lymphomas in Japanese macaques (Macaca fuscata).
    Veterinary pathology , 2015 May - 2015 May : 52(3)566-72
  • Bruce AG | Thouless ME | Haines AS | Pallen MJ | Grundhoff A | Rose TM
    Complete genome sequence of Pig-tailed macaque rhadinovirus 2 and its evolutionary relationship with rhesus macaque rhadinovirus and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus.
    PMC4403432 Journal of virology , 2015 Apr, - 2015 Apr, : 89(7)3888-909
  • Garrigues HJ | DeMaster LK | Rubinchikova YE | Rose TM
    KSHV attachment and entry are dependent on αVβ3 integrin localized to specific cell surface microdomains and do not correlate with the presence of heparan sulfate.
    PMC4157101 Virology , 2014 Sept. - 2014 Sept. : 464-465118-33
  • Stockinger DE | Fong DL | Vogel KW | Durning WM | Torrence AE | Rose TM | Staheli JP | Baldessari A | Murnane RD | Hukkannen RR
    Oral squamous cell carcinoma in a pigtailed macaque (Macaca nemestrina).
    PMC4067589 Comparative medicine , 2014 June - 2014 June : 64(3)234-9
  • 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.
    PMC3904427 Virology , 2014 Jan. 5 - 2014 Jan. 5 : 448196-209
  • 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.
    PMC3592352 Clinical and vaccine immunology : CVI , 2013 Mar. - 2013 Mar. : 20(3)409-19
  • 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.
    PMC3084728 PloS one , 2011 Apr, 29 - 2011 Apr, 29 : 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 Oct. - 2010 Oct. : 39(5)363-4; author reply 365-6
  • Boyce, R. and Rose, T.M.
    iCODEHOP: Interactive Consensus Degenerate Hybrid Oligonucleotide Primers
    http://dbmi-icode-01.dbmi.pitt.edu/i-codehop-context/ , 2010
  • 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.
    PMC2751581 Methods (San Diego, Calif.) , 2009 Sept. - 2009 Sept. : 49(1)32-41
  • 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.
    PMC2637656 Cellular microbiology , 2008 Apr, - 2008 Apr, : 10(4)863-75
  • 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. 10 - 2006 Oct. 10 : 354(1)103-15
  • Rose TM | Henikoff JG | Henikoff S
    CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design.
    PMC168931 Nucleic acids research , 2003 July 1 - 2003 July 1 : 31(13)3763-6
  • Hermouet S | Sutton CA | Rose TM | Greenblatt RJ | Corre I | Garand R | Neves AM | Bataille R | Casey JW
    Qualitative and quantitative analysis of human herpesviruses in chronic and acute B cell lymphocytic leukemia and in multiple myeloma.
    Leukemia , 2003 Jan. - 2003 Jan. : 17(1)185-95
  • Xie H | Cook GS | Costerton JW | Bruce G | Rose TM | Lamont RJ
    Intergeneric communication in dental plaque biofilms.
    PMC94835 Journal of bacteriology , 2000 Dec. - 2000 Dec. : 182(24)7067-9
  • Schultz ER | Rankin GW Jr | Blanc MP | Raden BW | Tsai CC | Rose TM
    Characterization of two divergent lineages of macaque rhadinoviruses related to Kaposi's sarcoma-associated herpesvirus.
    PMC112020 Journal of virology , 2000 May - 2000 May : 74(10)4919-28
  • Khandjian EW | Rose TM
    Disruption of LT-antigen/p53 complex by heat treatment correlates with inhibition of DNA synthesis during transforming infection with SV40.
    Biochemistry and cell biology = Biochimie et biologie cellulaire , 2000 - 2000 : 78(4)437-45
  • Lee, M., Olmstead, C. and Rose, T.M.
    Seqhelp and Web interface: A tool for assisting molecular sequence analysis.
    https://bir2.biology.washington.edu/seqhelp/seqhelpinput.html , 1999
  • Olmstead, C., Yarfitz, S. and Rose, T.M.
    Clustal W multiple alignment interface
    https://bir2.biology.washington.edu/clustalw/clustalw_form.html , 1999
  • Pantoja, P. and Rose, T.M.
    Invert DNA sequence
    http://bir.biology.washington.edu/Invert/invert1.html , 1999
  • Schultz, E. and Rose, T.M.
    Amino acid structure and letter code learning tool
    http://bir.biology.washington.edu/AminoAcidQuiz/AAQuiz.html , 1999
  • Bosch ML | Strand KB | Rose TM
    Gammaherpesvirus sequence comparisons.
    PMC110245 Journal of virology , 1998 Oct. - 1998 Oct. : 72(10)8458-9
  • Rose, T.M., Henikoff, S., Henikoff, J.
    CODEHOP: Consensus-Degenerate Hybrid Oligonucleotide Primers PCR primers designed from multiple protein sequence alignments
    http://www.blocks.fhcrc.org/blocks/codehop.html , 1998
  • Pantoja, P. and Rose, T.M.
    File Converter
    http://bir.biology.washington.edu/GPConverter/converter.html , 1998
  • Diamond C | Huang ML | Kedes DH | Speck C | Rankin GW Jr | Ganem D | Coombs RW | Rose TM | Krieger JN | Corey L
    Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma.
    The Journal of infectious diseases , 1997 Sept. - 1997 Sept. : 176(3)775-7
  • Wallace, J. and Rose, T.M.
    Restriction site analysis
    http://bir.biology.washington.edu/Restrict/restrict.html , 1997
  • Rose TM | Schultz ER | Sasaki GC | Kolattukudy PE | Shoyab M
    Nucleotide sequence and genomic structure of duck acyl-CoA binding protein/diazepam-binding inhibitor: co-localization with S-acyl fatty acid synthase thioesterase.
    DNA and cell biology , 1994 June - 1994 June : 13(6)669-78
  • Bruce AG | Linsley PS | Rose TM
    Oncostatin M.
    Progress in growth factor research , 1992 - 1992 : 4(2)157-70
  • Webb NR | Rose TM | Malik N | Marquardt H | Shoyab M | Todaro GJ | Lee DC
    Bovine and human cDNA sequences encoding a putative benzodiazepine receptor ligand.
    DNA (Mary Ann Liebert, Inc.) , 1987 Feb. - 1987 Feb. : 6(1)71-9
  • Rose TM | Weil R
    Characterization of the surface proteins of SV40-transformed mouse and human cells: absence of SV40-specific proteins.
    International journal of cancer. Journal international du cancer , 1983 May 15 - 1983 May 15 : 31(5)639-48
  • 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