Dan Streblow, Ph.D.

The focus of the Streblow laboratory is on defining the role of human cytomegalovirus (HCMV) in the development of vascular disease and chronic rejection of organ allografts. The role of CMV in these diseases is still uncharacterized. Dr. Streblow's lab studies the following topics:

1) Determining the mechanisms of HCMV-accelerated vascular disease through identification of the viral genes expressed during these diseases using a HCMV microarray chip developed by Dr. Streblow's laboratory in combination with the Shared Microarray Core at VGTI. Once identified, the function of these viral genes will be examined using in vitro and in vivo models of CMV-accelerated vascular disease.

2) Determining the mechanisms of CMV-accelerated vascular disease in both mouse models of atherosclerosis and rat organ transplantation models using a DNA microarray approach. The Streblow lab in conjunction with Dr. Susan Orloff’s laboratory at OHSU has determined RCMV in vivo gene expression in infected rats and has begun functional studies of these genes.

3) Determine viral and host gene expression during the development of atherosclerosis and transplant vascular sclerosis, the vascular lesion associated with chronic allograft rejection

4) determining the mechanisms of viral acceleration of chronic allograft rejection from latently infected donor, which is the most common cause of HCMV-associated disease in transplant patients associated with expression during the different stages of viremia associated with CMV including

5) Determining the function of CMV-encoded chemokine receptors in the context of viral pathogenesis and acceleration of vascular disease. Dr. Streblow's lab has also generated a rhesus macaque (RM) chikungunya virus (CHIKV) infection animal model to identify correlates of CHIKV pathogenesis and to test novel antivirals and vaccines. They are working on developing a Zika virus RM model.

Biography

Dr. Daniel Streblow received his B.S. in Pharmacology/Toxicology from the University of Wisconsin-Madison in 1992. He graduated from University of Wisconsin-Madison with a Ph.D. in Viral Pathogenesis in 1997. Dr. Streblow received a NIH post-doctoral fellowship and worked with Dr. Jay A. Nelson in the Department of Molecular Microbiology and Immunology at Oregon Health & Science University. He is currently an Associate Scientist at the Vaccine and Gene Therapy Institute and Research Assistant Professor at the Department of Molecular Microbiology and Immunology.

Publications

  • Hirsch AJ, Smith JL, Haese NN, Broeckel RM, Parkins CJ,Kreklywich C, DeFilippis VR, Denton M, Smith PP, Messer WB, Colgin LM, DucoreRM, Grigsby PL, Hennebold JD, Swanson T, Legasse AW, Axthelm MK, MacAllister R,Wiley CA, Nelson JA, Streblow DN. Zika Virus infection of rhesus macaques leadsto viral persistence in multiple tissues. PLoS Pathog. 2017 Mar9;13(3):e1006219. doi: 10.1371/journal.ppat.1006219. [PMID: 28278237]

  • Haese NN, Broeckel RM, Hawman DW, Heise MT, Morrison TE,Streblow DN. Animal Models of Chikungunya Virus Infection and Disease. J InfectDis. 2016 Dec 15;214(suppl 5):S482-S487. [PMID: 27920178]

  • Burwitz BJ, Malouli D, Bimber BN, Reed JS, Ventura AB,Hancock MH, Uebelhoer LS, Bhusari A, Hammond KB, Espinosa Trethewy RG, Klug A,Legasse AW, Axthelm MK, Nelson JA, Park BS, Streblow DN, Hansen SG, Picker LJ,Früh K, Sacha JB. Cross-Species Rhesus Cytomegalovirus Infection of CynomolgusMacaques. PLoS Pathog. 2016 Nov 9;12(11):e1006014. doi:10.1371/journal.ppat.1006014.[PMID: 27829026]

  • Caviness K, Bughio F, Crawford LB, Streblow DN, Nelson JA,Caposio P, Goodrum F. Complex Interplay of the UL136 Isoforms BalancesCytomegalovirus Replication and Latency. MBio. 2016 Mar 1;7(2):e01986. doi:10.1128/mBio.01986-15.[PMID: 26933055]

  • Uhrlaub JL, Pulko V,DeFilippis VR, Broeckel R, Streblow DN, Coleman GD, Park BS, Lindo JF, VickersI, Anzinger JJ, Nikolich-Žugich J. Dysregulated TGF-β ProductionUnderlies the Age-Related Vulnerability to Chikungunya Virus. PLoS Pathog. 2016Oct 13;12(10):e1005891. doi: 10.1371/journal.ppat.1005891.[PMID: 27736984]

  • Broeckel R, Haese N,Messaoudi I, Streblow DN;Nonhuman Primate Models of Chikungunya VirusInfection and Disease (CHIKV NHP Model). Pathogens. 2015 Sep 16;4(3):662-81.doi: 10.3390/pathogens4030662. [PMID: 26389957]

  • Chiang C, Beljanski V, Yin K, Olagnier D, Ben Yebdri F,Steel C, Goulet ML, DeFilippis VR, Streblow DN, Haddad EK, Trautmann L, Ross T,Lin R, Hiscott J.Sequence-Specific Modifications Enhance the Broad-SpectrumAntiviral Response Activated by RIG-I Agonists. J Virol. 2015 Aug;89(15):8011-25.doi: 10.1128/JVI.00845-15.[PMID: 26018150]

  • Streblow DN, Hwee YK, Kreklywich CN, Andoh T, Denton M,Smith P, Hart E, Broekel R, Pallett C, Rogers K, Streblow AD, Chuop M, Perry A,Slifka M, Messaoudi I, Orloff SL. Rat Cytomegalovirus Vaccine PreventsAccelerated Chronic Rejection in CMV-Naïve Recipients of Infected DonorAllograft Hearts. Am J Transplant. 2015 Jul;15(7):1805-16. doi:10.1111/ajt.13188. [PMID: 25766876]

  • Pal P, Fox JM, Hawman DW, Huang YJ, Messaoudi I, Kreklywich C, Denton M, Legasse AW, Smith PP, Johnson S, Axthelm MK, Vanlandingham DL, Streblow DN, Higgs S, Morrison TE, Diamond MS. Chikungunya viruses that escape monoclonal antibody therapy are clinically attenuated, stable, and not purified in mosquitoes. J Virol. 2014 Aug;88(15):8213-26. (doi: 10.1128/JVI.01032-14.) [PMID: 24829346, PMCID: PMC4135940] Epub 2014 May 14. 
  • Malouli D, Hansen SG, Nakayasu ES, Marshall EE, Hughes CM, Ventura AB, Gilbride RM, Lewis MS, Xu G, Kreklywich C, Whizin N, Fischer M, Legasse AW, Viswanathan K, Siess D, Camp DG 2nd, Axthelm MK, Kahl C, DeFilippis VR, Smith RD, Streblow DN, Picker LJ, Früh K. Cytomegalovirus pp65 limits dissemination but is dispensable for persistence. J Clin Invest. 2014 May 1;124(5):1928-44. [PMID: 24691437, PMCID: PMC4002596] Epub 2014 Apr 1.
  • Hakki M, Goldman DC, Streblow DN, Hamlin KL, Krekylwich CN, Fleming WH, Nelson JA. HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors. Biol Blood Marrow Transplant. 2014 Jan;20(1):132-5. (doi: 10.1016/j.bbmt.2013.10.019.) [PMID: 24161922, PMCID: PMC3922710] Epub 2013 Oct 23. 
  • Kreklywich CN, Smith PP, Jones CB, Cornea A, Orloff SL, Streblow DN. Fluorescence-based laser capture microscopy technology facilitates identification of critical in vivo cytomegalovirus transcriptional programs. Methods Mol Biol. 2014;1119:217-37. (doi: 10.1007/978-1-62703-788-4_13.) [PMID: 24639226]
  • Messaoudi I, Vomaske J, Totonchy T, Kreklywich CN, Haberthur K, Springgay L, Brien JD, Diamond MS, Defilippis VR, Streblow DN. Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity. PLoS Negl Trop Dis. 2013 Jul 25;7(7):e2343. (doi:10.1371/journal.pntd.0002343.) [PMID: 23936572, PMCID: PMC3723534] Print 2013.
  • Meyer C, Kerns A, Barron A, Kreklywich C, Streblow DN, Messaoudi I. Simian varicella virus gene expression during acute and latent infection of rhesus macaques. J Neurovirol. 2011 Dec;17(6):600-12. (doi: 10.1007/s13365-011-0057-y.) [PMID: 22052378, PMCID: PMC3286235] Epub 2011 Nov 4. 
  • Caposio P, Orloff SL, Streblow DN. The role of cytomegalovirus in angiogenesis. Virus Res. 2011 May;157(2):204-11. (doi: 10.1016/j.virusres.2010.09.011.) [PMID: 20869406, PMCID: PMC3040784] Epub 2010 Oct 1.
  • Botto S, Streblow DN, DeFilippis V, White L, Kreklywich CN, Smith PP, Caposio P. IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin. Blood. 2011 Jan 6;117(1):352-61. (doi: 10.1182/blood-2010-06-291245.) [PMID: 20930069, PMCID: PMC3037756] Epub 2010 Oct 7.
  • Meyer C, Grey F, Kreklywich CN, Andoh TF, Tirabassi RS, Orloff SL, Streblow DN. Cytomegalovirus microRNA expression is tissue specific and is associated with persistence. J Virol. 2011 Jan;85(1):378-89. (doi: 10.1128/JVI.01900-10.) [PMID: 20980502, PMCID: PMC3014154] Epub 2010 Oct 27.
  • White LK, Sali T, Alvarado D, Gatti E, Pierre P, Streblow D, Defilippis VR. Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff. J Virol. 2011 Jan;85(1):606-20. (doi: 10.1128/JVI.00767-10.) [PMID: 20962078, PMCID: PMC3014158] Epub 2010 Oct 20.
  • Vomaske J, Varnum S, Melnychuk R, Smith P, Pasa-Tolic L, Shutthanandan JI, Streblow DN. HCMV pUS28 initiates pro-migratory signaling via activation of Pyk2 kinase. Herpesviridae. 2010 Dec 7;1(1):2. (doi: 10.1186/2042-4280-1-2.) [PMID: 21429240, PMCID: PMC3050435] 
  • Smith MS, Goldman DC, Bailey AS, Pfaffle DL, Kreklywich CN, Spencer DB, Othieno FA, Streblow DN, Garcia JV, Fleming WH, Nelson JA. Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe. 2010 Sep 16;8(3):284-91. (doi: 10.1016/j.chom.2010.08.001.) [PMID: 20833379, PMCID: PMC2945885] 
  • Vomaske J, Nelson JA, Streblow DN. Human Cytomegalovirus US28: a functionally selective chemokine binding receptor. Infect Disord Drug Targets. 2009 Nov;9(5):548-56. [PMID: 19594424, PMCID: PMC3496389] 
  • Vomaske J, Melnychuk RM, Smith PP, Powell J, Hall L, DeFilippis V, Früh K, Smit M, Schlaepfer DD, Nelson JA, Streblow DN. Differential ligand binding to a human cytomegalovirus chemokine receptor determines cell type-specific motility. PLoS Pathog. 2009 Feb;5(2):e1000304. (doi: 10.1371/journal.ppat.1000304.) [PMID: 19229316, PMCID: PMC2637432] Epub 2009 Feb 20.
  • Medigeshi GR, Hirsch AJ, Streblow DN, Nikolich-Zugich J, Nelson JA. West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of alphavbeta3 integrin. J Virol. 2008 Jun;82(11):5212-9. (doi: 10.1128/JVI.00008-08.) [PMID: 18385233, PMCID: PMC2395215] Epub 2008 Apr 2.
  • Streblow DN, van Cleef KW, Kreklywich CN, Meyer C, Smith P, Defilippis V, Grey F, Früh K, Searles R, Bruggeman C, Vink C, Nelson JA, Orloff SL. Rat cytomegalovirus gene expression in cardiac allograft recipients is tissue specific and does not parallel the profiles detected in vitro. J Virol. 2007 Apr;81(8):3816-26. [PMID: 17251289, PMCID: PMC1866122] Epub 2007 Jan 24.
  • Streblow DN, Kreklywich CN, Smith P, Soule JL, Meyer C, Yin M, Beisser P, Vink C, Nelson JA, Orloff SL. Rat cytomegalovirus-accelerated transplant vascular sclerosis is reduced with mutation of the chemokine-receptor R33. Am J Transplant. 2005 Mar;5(3):436-42. [PMID: 15707397] 
  • Streblow DN, Vomaske J, Smith P, Melnychuk R, Hall L, Pancheva D, Smit M, Casarosa P, Schlaepfer DD, Nelson JA. Human cytomegalovirus chemokine receptor US28-induced smooth muscle cell migration is mediated by focal adhesion kinase and Src. J Biol Chem. 2003 Dec 12;278(50):50456-65. [PMID: 14506272] Epub 2003 Sep 22.
    Streblow DN, Nelson JA. Models of HCMV latency and reactivation. Trends Microbiol. 2003 Jul;11(7):293-5. [PMID: 12875809]
  • Streblow DN, Kreklywich C, Yin Q, De La Melena VT, Corless CL, Smith PA, Brakebill C, Cook JW, Vink C, Bruggeman CA, Nelson JA, Orloff SL. Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants. J Virol. 2003 Feb;77(3):2182-94. [PMID: 12525653, PMCID: PMC140920]
  • Heinzel AS, Grotzke JE, Lines RA, Lewinsohn DA, McNabb AL, Streblow DN, Braud VM, Grieser HJ, Belisle JT, Lewinsohn DM. HLA-E-dependent presentation of Mtb-derived antigen to human CD8+ T cells. J Exp Med. 2002 Dec 2;196(11):1473-81. [PMID: 12461082, PMCID: PMC2194265] 
  • Jarvis MA, Fish KN, Söderberg-Naucler C, Streblow DN, Meyers HL, Thomas G, Nelson JA. Retrieval of human cytomegalovirus glycoprotein B from cell surface is not required for virus envelopment in astrocytoma cells. J Virol. 2002 May;76(10):5147-55. [PMID: 11967330, PMCID: PMC136176]