Skip to main content

Search
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

Making a Difference

  • 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 NameAward DescriptionAwarded ByAward Date
Outstanding MentorSchool of Public Health and Community Medicine 2007
K02 Independent Scientist AwardNational Institutes of Health 2001 - 2006
Outstanding TeacherSchool of Public Health and Community Medicine 1998
Shannon AwardNational Institutes of Health 1996

Publications

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 , July 24, 2014: 464-465118-133
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
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
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 , Dec. 2013: 87(24)13676-93
Nuclear Fragile X Mental Retardation Protein Is localized to Cajal Bodies.
PLoS genetics , Oct. 2013: 9(10)e1003890
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 , March 2013: 20(3)409-19
Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.
PLoS pathogens , 2012: 8(10)e1002962
Conservation of complex nuclear localization signals utilizing classical and non-classical nuclear import pathways in LANA homologs of KSHV and RFHV.
PloS one , April 2011: 6(4)e18920
Comment on Mugisha et al. J Med Primatol 2010; 39: 71-76.
Journal of medical primatology , April 2010
iCODEHOP: Interactive Consensus Degenerate Hybrid Oligonucleotide Primers
http://dbmi-icode-01.dbmi.pitt.edu/i-codehop-context/ , 2010
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 , Nov. 2009: 205
Consensus-degenerate hybrid oligonucleotide primers (CODEHOPs) for the detection of novel viruses in non-human primates.
Methods (San Diego, Calif.) , Sept. 2009: 32-41
iCODEHOP: a new interactive program for designing COnsensus-DEgenerate Hybrid Oligonucleotide Primers from multiply aligned protein sequences.
Nucleic acids research , July 2009: W222-8
ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosis.
Cellular microbiology , April 2008: 863-75
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 , Feb. 2008: 1570-80
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 , Dec. 2006: 3529-38
RFHVMn ORF73 is structurally related to the KSHV ORF73 latency-associated nuclear antigen (LANA) and is expressed in retroperitoneal fibromatosis (RF) tumor cells.
Virology , Oct. 2006: 103-15
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 , March 2006: 11
Evolution of the acyl-CoA binding protein (ACBP).
The Biochemical journal , Dec. 2005: 299-307
CODEHOP-mediated PCR - a powerful technique for the identification and characterization of viral genomes.
Virology journal , March 2005: 20
Development of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons.
Virology journal , Jan. 2005: 2
CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design.
Nucleic acids research , July 2003: 3763-6
Amino acid structure and letter code learning tool
http://bir.biology.washington.edu/AminoAcidQuiz/AAQuiz.html , 1999
Invert DNA sequence
http://bir.biology.washington.edu/Invert/invert1.html , 1999
Clustal W multiple alignment interface
https://bir2.biology.washington.edu/clustalw/clustalw_form.html , 1999
Seqhelp and Web interface: A tool for assisting molecular sequence analysis.
https://bir2.biology.washington.edu/seqhelp/seqhelpinput.html , 1999
File Converter
http://bir.biology.washington.edu/GPConverter/converter.html , 1998
CODEHOP: Consensus-Degenerate Hybrid Oligonucleotide Primers PCR primers designed from multiple protein sequence alignments
http://www.blocks.fhcrc.org/blocks/codehop.html , 1998
Restriction site analysis
http://bir.biology.washington.edu/Restrict/restrict.html , 1997
Various patents created
,

Presentations

Presentations TitleEventLocationDate
"Kaposis sarcoma-associated herpesvirus (KSHV) and homologs in non-human primates"Uganda Research in Progress MeetingsFred Hutchinson Cancer Research Center, Vaccine Infectious Disease DivisionApril 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 agentsHelsinki, FinlandAug. 12, 2011
"Herpesvirus activation in SIV vaccine studies"Infectious Disease Science ProgramFred Hutchinson Cancer Research Center Vaccine Infectious Disease DivisionNov. 4, 2010
"The pig-tailed macaque rhadinovirus is associated with T-cell lymphomas in its natural host"International Workshop for KSHV/HHV8 and Related AgentsLos Angeles, CASept. 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 DiseasesUniversity of WAMay 13, 2010
"Infectious etiology of AIDS-related malignancies"Infectious Disease Senior Faculty SeminarUniversity of WashingtonNov. 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 AgentsCharleston, South CarolinaSept. 14, 2009
"AIDS-related malignancies, etiological herpesviruses and the oral environment"Cross-Disciplinary Dental Science Seminar, Oral Biology 575University of WashingtonMay 11, 2009
"Kaposis sarcoma associated herpesvirus and homologs in macaques"Veterinarian Grand Rounds, Washington National Primate Research CenterUniversity of WashingtonJan. 23, 2009

Research Funding

Grant TitleGrantorAmountAward Date
Point-of-care diagnosis and surveillance of known and emerging influenza viruses - R01 AI111303NIH/NIAID $855,731 annual directsMarch 15, 2014 - Feb. 28, 2019
Oral pathogenesis and host interactions of KSHV infection - P01 DE021954NIH/NIDCR $993,231 + $120,000 annual directsJune 7, 2011 - April 30, 2016
POC molecular method for detection of known and emerging respiratory virusesNIH/NIDCR $300,885.00July 1, 2009
Viral and cellular factors involved in KSHV entry in cells of the oral mucosaNIH/NIDCR $1,125,000.00Aug. 15, 2007
Herpesvirus latency and reactivation in macaque models of human diseaseNIH/NCRR $1,680,995.00July 1, 2007

Primary Office

Seattle Children's Research Institute
JMB - 8 - Infectious Disease
1900 - 9th Ave
Seattle, WA 98101
206-987-2073

Find a Doctor or Researcher

Find a Doctor or Researcher

Type the first or last name you are searching for or select a specialty.

Doctor or Researcher Name:

More search options