Daniel Streblow, Ph.D.

The focus of my 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. My lab will study 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 his 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 associatated 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 was recently awarded an ONPRC pilot project grant to study Chikungunya in a NHP 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 Assistant Scientist at the Vaccine and Gene Therapy Institute and Department of Molecular Microbiology and Immunology.



Publications

1. Pauza, CD, Trivedi P, Johnson E, Meyers KK, Streblow DN, Malkovsky M, Emau P, Schultz KT and Salvato MS. 1994.  Acquired resistance to mucosal SIV infection after low dose intrarectal inoculation: The roles of virus selection and CD8-mediated T cell immunity.  Colloques des "Cent Gardes", 8th, Marnes-la-Coquette, Paris, France, 22-24 October 1993.  Proceedings:  Retrovirses of Human AIDS and Related Animal Diseases.  M. Girard and L. Vallette (eds.).  Foundation Marcel Merieux, Lyon.

2. Trivedi P, Meyer KK, Streblow DN, Preuninger BL, Schultz KT, and Pauza CD.  1994.  Selective amplification of SIV genotypes after intrarectal inoculation of rhesus monkeys.  J. Virol. 62:7649-7653.

3. Pauza CD and Streblow DN. Antiviral approaches to HIV-1 infection based on virus structure and the host pathogen interaction.  Curr. Topics Microbiol and Immunol.  1995. pp117-132.

4 Streblow, DN, Kitabwalla M, Malkovsky M, and Pauza CD. 1998.  Cyclophilin A Modulates    
Processing of p55Gag from HIV Type 1:  Mechanism for Antiviral Effects of Cyclosporine A.     
Virology, 245:197-202.

5. Streblow DN, Kitabwalla M, and Pauza CD. 1998.  Gag Protein from Human Immunodeficiency Virus Type I Assembles in the Absence of Cyclophilin A.  Virology, 252:228-234.

6. Streblow DN, Soderberg-Naucler C, Vieira J, Smith P, Ruchti F, Mattison K, and Nelson JA.  1999.  Vascular Smooth Muscle Cell Migration is Induced by the HCMV Chemokine Receptor US29.  Cell, 99:511-21.

7. De La Melena VT, Kreklywich CN, Streblow DN, Yin Q, Cook JW, Nelson JA, Orloff SL. The kinetics and development of CMV-accelerated transplant vascular sclerosis in rat cardiac allografts is linked to early presence of virus in the graft. Surgical Forum 2000;LI:350-2.

8. Murphy, E.A., Streblow, D.N., Nelson, J.A., and M.F. Stinski. The HCMV IE86 protein can block cell cycle progression after inducing transition into the S phase of permissive cells. Journal of Virology. 74 (15): 7108-18.

9. Söderberg-Nauclér C, DN Streblow, KN Fish, J Allan-Yorke, P Smith , JA Nelson. Reactivation of Latent HCMV in CD14+ Monocytes is Differentiation Dependent. Journal of Virology. 2001 Aug;75(16):7543-54.

10. De La Melena VT, Kreklywich CN, Streblow DN, Yin Q, Cook JW, Soderberg-Naucler, C, Bruggeman CA, Nelson JA, Orloff SL. The kinetics and development of CMV-accelerated transplant vascular sclerosis in rat cardiac allografts is linked to early increase in chemokine expression and presence of virus. Transplant Proc 2000; 33: 1822-3.

11. D. N. Streblow, S. L. Orloff, and J. A. Nelson. Do Pathogens Accelerate Atherosclerosis? Journal of Nutrition. 2001; 131: 2798-2804.

12. De La Melena VT, Kreklywich CN, Streblow DN, Yin Q, Cook JW, Soderberg-Naucler C, Bruggeman CA, Nelson JA, Orloff SL. Kinetics and development of CMV-accelerated transplant vascular sclerosis in rat cardiac allografts is linked to early increase in chemokine expression and presence of virus. Transplant Proc. 2001 Feb-Mar;33(1-2):1822-3.

13. D. N. Streblow, S. L. Orloff, and Jay A. Nelson. The HCMV Chemokine Receptor US28 is a Potential Target in Vascular Disease. 2001. Current Drug Targets-Infectious Disorders, Vol 1. No. 2; 151-8.

14. S. L. Orloff, D. N. Streblow, C. Soderberg-Naucler, Q. Yin, C.N. Kreklywich, C.L. Corless, P.A. Smith, C.B. Loomis, L.K. Mills, J.W. Cook, T. De La Melena, C.A. Bruggeman, J.A. Nelson, and Cynthia R. Wagner.  Elimination of Donor-Specific Alloreactivity Prevents Cytomegalovirus-Accelerated Chronic Rejection in Rat Small Bowel and Heart Transplants. Transplantation. 2002 73(5);679-88.

15. M.A. Jarvis, K.N. Fish, C. Soderberg-Naucler, D.N. Streblow, H.L. Meyers, G. Thomas and J.A. Nelson.  Retrieval of human cytomegalovirus glycoprotein B from cell surface is not required for virus envelopment in astrocytoma cells. Journal of Virolog. 2002 May;76(10):5147-55.

16. Le Roy E, Baron M, Faigle W, Clement D, Lewinsohn DM, Streblow DN, Nelson JA, Amigorena S, Davignon JL. Infection of APC by human cytomegalovirus controlled through recognition of endogenous nuclear immediate early protein 1 by specific CD4(+) T lymphocytes. Journal of  Immunology. 2002 Aug 1;169(3):1293-301.

17. A.S. Heinzel, J.E. Grotzke, R.A. Lines, D.A. Lewinsohn, A.L. McNabb, D.N. Streblow, V.M. Braud, H.J. Grieser, J.T. Belisle, and D.M. Lewinsohn.  HLA-E-dependent Presentation of Mtb-derived Antigen to Human CD8+ T Cells.  J. Exp. Med. 2002;196 1473-1481.

18. D. N. Streblow, C.N. Kreklywich, Q. Yin, V.T. De La Melena, J.W. Cook JW, Corless, C.L.,
Vink, C., Bruggeman, C.A., Nelson JA, and S.L. Orloff. Upregulation Of Chemokine       
Expression Correlates With The Development Of Cytomegalovirus-Accelerated Chronic   
Rejection In Rat Heart Transplants. J. Virology, February 2003; 77(3):2182-2194.

19. Hsia, D., Hauck, C., Mitra, S., Streblow, D., Nelson, Ilic, D., Li, E., Nemerow, G., Leng, J., Cheresh, D., and D, Schlaepfer.  Differential regulation of cell motility and invasion by FAK Journal of Cell Biology, 2003; Vol 160 (5),  pp753-767.

20. Streblow DN, Nelson JA. Models of HCMV latency and reactivation.  Trends Micro. 2003    
July; 11 (7):293-5

21. Streblow DN, Vomaske J, Smith P, Melnychuk R, Hall L, Pancheva D, Smit M, Casarosa P, Schlaepfer D, Nelson JA. 2003. HCMV chemokine receptor US28-induced smooth muscle cell migration is mediated by focal adhesion kinase and Src. J Bio Chem. Dec 12; 278 (50):50456-65.

22. D. Ilic, B. Kovac, K. Johkura, D.D. Schlaepfer, N. Tomasevic, Q. Han, J. Kim, K. Howerton, C. Baumbusch, N. Ogiwara, D.N. Streblow, J.A. Nelson, P. Dazin, Y. Shino, K. Sasaki, and C.H. Damsky. 2004. FAK promotes organization of fibronectin matrix and fibrillar adhesions. Journal of Cell Science. Jan 15;117(Pt 2):177-87.

23. C. Allal, Buisson-Brenac C, Marion V, Claudel-Renard C, Faraut T, Dal Monte P, Streblow D, Record M, Davignon JL. 2004. Human cytomegalovirus carries a cell-derived phospholipase A2 required for infectivity. Journal of Virology. Jul;78(14):7717-26.

24. R.M. Melnychuk, D.N. Streblow, P. Smith, A.J. Hirsch, D. Pancheva, J.A. Nelson. 2004. The human cytomegalovirus encoded G-protein coupled receptor US28 mediates smooth muscle cell migration through Ga12. Journal of Virology. Aug;78(15):8382-91.

25. Varnum SM, Streblow DN, Monroe ME, Smith P, Auberry KJ, Pasa-Tolic L, Wang D, Camp DG 2nd, Rodland K, Wiley S, Britt W, Shenk T, Smith RD, Nelson JA. 2004. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. Journal of Virology. Oct;78(20):10960-6.

26. D. N. Streblow, C. N. Kreklywich, P. Smith, J. L. Soule, C. Meyer, M. Yin, P. Beisser, C. Vink, J. A. Nelson, and S. L. Orloff. 2005. Rat Cytomegalovirus Accelerated Transplant Vascular Sclerosis is Reduced with Mutation of the Chemokine Receptor R33. American Journal of Transplantation 5(3): 436-42.

27. R. Melnychuk, F. Ruchti, P. Smith, C. Kreklywich, J. Vomaske, L. Hall, S. Orloff, J. Nelson, and D.N. Streblow. 2005. The Mouse Cytomegalovirus-Encoded Chemokine Receptor M33 Mediates Vascular Smooth Muscle Cell Migration. Journal of Virology. Aug;79(16):10788-95.

28. D. A. Hsia, S. Lim, J. A. Bernard-Trifilo, S. K. Mitra, S. Tanaka, J. den Hertog, D. N. Streblow, D. Ilic, M. H. Ginsberg, and D. D. Schlaepfer. 2005 Inegrin a4b1 Promotes FAK-Independent Cell Motility via a4 Cytomplasmic Domain-Specific Activation of c-Src. Molecular and Cellular Biology. Nov;25(21).

29. S. Delamas, L. Martin, M. Baron, J.A. Nelson, D.N. Streblow, and J-L. Davignon. 2005. Optimization of CD4+ T Lymphocyte Response to Human Cytomegalovirus Nuclear IE1 Protein Through Modifications of Both Size and Cellular Localization. Journal of Immunology. Nov 15;175(10):6812-9.

30. H.H. Krishnan, N. Sharma-Walia, D.N. Streblow, P.P. Naranatt, and B. Chandran. 2006. Focal adhesion kinase is critical for entry of Kaposi's sarcoma-associated herpesvirus into target cells. Journal of Virology. 2006 Feb;80(3):1167-80.

31. D.N. Streblow, S.M. Varnum, R.D. Smith, and J.A. Nelson. 2006. A proteomics analysis of Human Cytomegalovirus Particles. Cytomegaloviruses: Molecular Biology and Immunology. pp.91-110.

32. K. Rafiq, M.A. Kolpakov, M. Abdelfettah, D.N. Streblow, A. Hassid, L.J. Dell'italia, A. Sabri.  2006. Role of protein tyrosine phosphatase SHP2 in focal adhesion kinase downregulation during neutrophil cathepsin G-induced cardiomyocytes anoikis. Journal of Biological Chemistry. 14;281(28):19781-92.

33. J.L. Soule, D.N. Streblow, T.F. Andoh, C.N. Kreklywich, and S.L. Orloff. 2006. Cytomegalovirus accelerates chronic allograft nephropathy in a rat renal transplant model with associated provocative chemokine profiles. Transplant Proceedings. Dec;38(10):3214-20.

34. D.N. Streblow, K.W. van Cleef, C.N. Kreklywich, C. Meyer, P. Smith, V. Defilippis, F. Grey, K. Fruh, R. Searles, C. Bruggeman, C. Vink, J.A. Nelson, and S.L. Orloff. 2007 Rat cytomegalovirus gene expression in cardiac allograft recipients is tissue specific and does not parallel the profiles detected in vitro. Journal of Virology. Apr;81(8):3816-26.

35. D.N. Streblow, S.L. Orloff, and J.A. Nelson. 2007. Acceleration of Allograft Failure by Cytomegalovirus. Current Opinion in Immunology. Oct;19(5):577-82.

36. D.N. Streblow, C.N. Kreklywich, T. Andoh, A.V. Moses, J. Dumortier, P.P. Smith, V. Defilippis, K. Fruh, J.A. Nelson, and S.L. Orloff. 2008. The Role of Angiogenic and Wound Repair Factors During CMV-Accelerated Transplant Vascular Sclerosis in Rat Cardiac Transplants. American Journal of Transplantation. Feb;8(2):277-87.

37. D. Verzijl, S. Storelli, D.J. Scholten, L. Bosch, T.A. Reinhart, D.N. Streblow, C.P. Tensen, C.P. Fitzsimons, G.J.R. Zaman, J.E. Pease, I.J.P. de Esch, M.J. Smit and R. Leurs. 2008. Non-competitive antagonism and inverse agonism as mechanism of action of non-peptidergic antagonists at primate and rodent CXCR3 chemokine receptors. Journal of Pharmacology and Experimental Therapuetics. May;325(2):544-55.

38. J. Dumortier, D.N. Streblow, A.V. Moses, J.M. Jacobs, C.N. Kreklywich, D. Camp, R.D. Smith, S.L. Orloff, and J.A. Nelson. 2008. Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing. Journal of Virology. 2008 Jul;82(13):6524-35. Epub 2008 Apr 30.

39. D.N. Streblow, J. Dumortier, A.V. Moses, S.L. Orloff, and J.A. Nelson. 2008. Mechanisms of Cytomegalovirus-Accelerated Vascular Disease: Induction of Paracrine Factors that Promote Angiogenesis and Wound Healing. Current Topics in Microbiology and Immunology: Human Cytomegalovirus Eds. T.E. Shenk and M.F. Stinski. 2008;325:397-415.

40.  E.R. Kern, E.E. Sztul, S.L. Daily, A.L. Perry, S.L. Frederick, C.B. Hartline, S.M. Varnum, R.D. Smith, D.N. Streblow, and M.N. Prichard. Human Cytomegalovirus UL97 Kinase Activity Is Required For The Hyper-phosphorylation Of RB And Inhibits The Formation Of Nuclear Aggresomes. Journal of Virology May;82(10):5054-67

41. G.R. Medigeshi, A.J. Hirsch, D.N. Streblow, J. Nikolich-Zugich, and J.A. Nelson. 2008. West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of {alpha}v{beta}3 integrin. Journal of Virology Jun;82(11):5212-9. Epub 2008 Apr 2.

42. J. J. Vomaske, R.M. Melnychuk, P.P. Smith, J. Powell, L. Hall, V. DeFillipis, K. Früh, M. Smit, D.D. Schlaepfer, J.A. Nelson, and D.N. Streblow. .Differential Ligand Binding to a Human Cytomegalovirus Chemokine Receptor Determines Cell Type-Specific Motility. PLOS Pathogens Feb: 5(2) e10000304. Epub 2009 Feb 20.

43. C. C. Baca Jones, C.N. Kreklywich, I. Messaoudi, J. Vomaske, E. McCartney, S.L. Orloff, J.A. Nelson, and D.N. Streblow. 2009. Rat Cytomegalovirus Infection Depletes MHC I and II in Bone Marrow Derived Dendritic Cells. Virology May 25;388(1):78-90. Epub 2009 Apr 5.

44. J. Vomaske and D.N. Streblow. 2009 Human Cytomegalovirus US28: A Functionally Selective Chemokine Binding Receptor. 2009. Current Drug Targets-Infectious Disorders. Epub 2009 Oct 1.

 

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