OHSU

Daniel N. Streblow

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. In the past we have utilized microarray technology to compare the CMV transcriptome from cells infected in culture vs. tissues from rats, mice and humans. Currently, we are using NextGen Sequencing to determine the unbiased CMV transcriptome and these studies will revolutionize our understanding of the viral genes that are expressed under disease conditions. Once the viral genes are 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 rat organ transplantation and rat carotid injury models using cellular- and virus-specific DNA microarrays. The Streblow lab, in conjunction with Dr. Susan Orloff's laboratory at OHSU, has determined both cellular and RCMV in vivo gene expression in infected rats and has begun functional studies of these genes. These studies include the identification of biomarkers of CMV-accelerated vascular disease and allograft rejection in samples from our rat model and human heart transplant patients. 3) Determining the immunological mechanisms of viral acceleration of chronic allograft rejection from latently infected donors, which is the most common cause of HCMV-associated disease in transplant patients. 4) Determining the function of CMV-encoded chemokine receptors in the context of viral pathogenesis and acceleration of vascular disease. 5) Determining the role of age-related susceptibility to Chikungunya virus infection and disease in an NHP model.

Biography

Dr. Daniel Streblow received his B.S. in Pharmacology/Toxicology from the University of Wisconsin-Madison in 1992. He graduated from the University of Wisconsin-Madison with a Ph.D. in Viral Pathogenesis in 1997. Dr. Streblow received an 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

D.N. Streblow, Soderberg-Naucler, C., Vieira, J., Smith, P., Ruchti, F., Mattison, K., and J.A. Nelson. 1999. Vascular smooth muscle cell migration is induced by the Human Cytomegalovirus chemokine receptor US28. Cell. 99:511-21.

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

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.

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.

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. 2009. Differential ligand binding to a human cytomegalovirus chemokine receptor determines cell type-specific motility. PLOS Pathogens Feb:5(2) e10000304. Epub 2009 Feb 20.

J. Vomaske, S.M. Varnum, R. Melnychuk, P. Smith, L. Pasa-Tolic L, J.I. Shutthanandan, and D.N. Streblow. 2010. HCMV pUS28 initiates pro-migratory signaling via activation of PYK2 kinase. Herpesviridae. Dec 7:1(1):2.

L. White, T. Sali, D. Alvarado, E. Gatti, P. Pierre, D.N. Streblow and V.R Defilippis. 2011.Chikungunya virus induces IPS-1-dependent innate immune activation and PKR-independent translational shutoff. J. Virol. Jan;85(1):606-20.

C. Meyer, F. Grey, C.N. Kreklywich, T.F. Andoh, R.S. Tirabassi, S.L. Orloff and D.N. Streblow. 2011. Cytomegalovirus miRNA expression is tissue specific and associated with persistence. J. Virol. Jan;85(1):378-89.

S.L. Orloff, Y.K. Hwee, C.N. Kreklywich, T.F. Andoh, E. Hart, P. Smith, I. Messaoudi and D.N. Streblow. 2011 Cytomegalovirus latency promotes cardiac lymphoid neogenesis and accelerated allograft rejection in CMV naïve recipients. American Journal of Transplantation. Jan;11(1):45-55.

C. Meyer, A. Kerns, A. Barron, C. Kreklywich, D.N. Streblow, and I. Messaoudi. 2011. Simian varicella virus gene expression during acute and latent infection of rhesus macaques. J. Neurovirol.  Nov 4. [Epub ahead of print].