University of Rochester School of Medicine
Department of Microbiology & Immunology 
Faculty Profile

Ph.D. (1987)
University of Nebraska

Steve Dewhurst
  Sr. Associate Dean for Basic Research
Professor of Microbiology & Immunology and of Oncology

Primary Appointment:
 Microbiology & Immunology

GEBS Cluster Affiliations:
 IMV - Immunology, Microbiology, and Virology
 NS - Neuroscience

Link to Laboratory Server and Web Page

Contact Information
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester, New York 14642
 Phone: (585) 275-3216
Fax: (585) 473-2361
E-Mail: stephen_dewhurst@urmc.rochester.edu
Research Focus
HIV Vaccine Development; NeuroAIDS; Oncolytic Virus Vectors; Influenza Virology
Research Overview
HIV Vaccine Development: We are using bacteriophage lambda as a scaffold to display the HIV-1 envelope glycoprotein in a dense, repetitive array that is expected to elicit more potent humoral immune responses against this key virus antigen. We are also testing whether it may be possible to immunize against host cell proteins involved in virus infection, in order to produce a vaccine capable of preventing the sexual transmission of HIV-1 infection.
Novel Therapeutic Approaches to NeuroAIDS: Our laboratory is part of a NIH-funded translational program project directed by Handy Gelbard, that is designed to develop new therapies for HIV-1 associated neurocognitive disorder (HAND). HAND is a major clinical problem that continues to grow despite the availability of effective antiretroviral therapies - in part because many antiviral drugs fail to penetrate the central nervous system. Our focus is on mixed lineage kinase (MLK)-3, an upstream kinase that regulates the activity of pro-apoptotic and pro-inflammatory kinases such as Jun N-terminal kinase (JNK) and p38 mitogen-associated protein kinase. We are examining the role of MLK-3 in the pathogenesis of HAND and other neurologic diseases, and developing protective strategies that target this enzyme, in collaboration with Handy Gelbard, Sanjay Maggirwar and Giovanni Schifitto.
Oncolytic Virus Vectors for Cancer Therapy: Adenovirus vectors that replicate selectively in tumor cells are being developed for the treatment of human cancers. In collaboration with Baek Kim, we are testing whether one can create improved, conditionally replicating adenoviuses, by using mutations in the viral DNA polymerase that permit DNA synthesis only in cells that contain high amounts of dNTPs (such as cancer cells).
Influenza Virus Research: We participate in the UR's New York Influenza Center of Excellence, one of 6 national centers that are part of the CEIRS consortium (Centers of Excellence for Influenza Research and Surveillance). In collaboration with Baek Kim and Toru Takimoto, we are studying the RNA polymerase complexes from both human and avian influenza virus strains, so as to understand how the RNA polymerase may influence viral pathogenicity, host adaptation and mutation synthesis.
Recent Publications
Bimber BN, Chugh P, Giorgi EE, Kim B, Almudevar AL, Dewhurst S, O'Connor DH, Lee HY Nef gene evolution from a single transmitted strain in acute SIV infection. Retrovirology. 2009;6:57

Volcy K, Dewhurst S Proteasome inhibitors enhance bacteriophage lambda (lambda) mediated gene transfer in mammalian cells. Virology. 2008 Dec 6;
Norman JP, Perry SW, Reynolds HM, Kiebala M, De Mesy Bentley KL, Trejo M, Volsky DJ, Maggirwar SB, Dewhurst S, Masliah E, Gelbard HA HIV-1 Tat activates neuronal ryanodine receptors with rapid induction of the unfolded protein response and mitochondrial hyperpolarization. PLoS ONE. 2008;3(11):e3731

Bradel-Tretheway BG, Kelley Z, Chakraborty-Sett S, Takimoto T, Kim B, Dewhurst S The human H5N1 influenza A virus polymerase complex is active in vitro over a broad range of temperatures, in contrast to the WSN complex, and this property can be attributed to the PB2 subunit. J Gen Virol. 2008 Dec;89(Pt 12):2923-32

Diamond, T.L., Roshal, M., Jamburuthugoda, V., Reynolds, H.M., Merriam, A.R., Lee, K.Y., Balakrishnan, M., Bambara, R.A., Planelles, V., Dewhurst, S., and Kim, B. Macrophage tropism of HIV-1 depends upon efficient cellular dNTP utilization by reverse transcriptase. J. Biol. Chem. 271:51545-53, 2004.
Fan, S., Maguire, C.A., Ramirez, S.H., Bradel-Tretheway, B., Sapinoro, R., Sui, Z., Chakraborty-Sett, S., Dewhurst, S. Valproic acid enhances gene expression from viral gene transfer vectors. J. Virol. Meth. 125:23-33, 2005.
Dou, H., Ellison, B., Bradley, J., Kasiyanov, A., Poluektova, L., Xiong, H., Maggirwar, S., Dewhurst, S., Gelbard, H.A., and Gendelman, H.E. Neuroprotective mechanisms of lithium in murine HIV-1 encephalitis. J. Neurosci. 25: 8375-85, 2005.
Zanghi, C.N. *, Lankes, H.A. *, Bradel-Tretheway, B., Wegman, J., and Dewhurst, S. A simple method for displaying recalcitrant proteins on the surface of bacteriophage lambda. Nucleic Acids Res. 33:e160, 2005. *: Co-First Authors.
Maguire, C.A., Sapinoro, R., Girgis, N., Rodriguez-Colon, S.M., Ramirez, S.H., Williams, J., and Dewhurst, S. Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and avb3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens. Vaccine 24(5):671-682, 2006.
Sui, Z. *, Fan, S. *, Sniderhan, L., Gelbard, H.A., Dewhurst, S and Maggirwar, S. Inhibition of mixed lineage kinase (MLK)-3 prevents HIV-1 Tat-mediated neurotoxicity and monocyte activation. J. Immunol. 177:702-11, 2006. *: Co-First Authors.
Santos, K., Duke, C., Rodriguez-Colon, S.M., Dakwar, A., Fan, S., Federoff, H.J., Keefer, M.C., Bowers, W.J., Dewhurst, S. In vivo immunogenicity of a helper-free HSV-1 amplicon vector encoding HIV-1 Gag is correlated with gene expression in cultured primary dendritic cells. Vaccine 25:1634-1646, 2007.
Chugh, P., Fan, S., Planelles, V., Maggirwar, S.B., Dewhurst, S., and Kim, B. Infection of Human Immunodeficiency Virus and Intracellular Viral Tat Protein Exert a Pro-Survival Effect in a Human Microglial Cell Line. J. Mol. Biol. 366:67-81, 2007.
Lankes, H.A. *, Zanghi, C.N. *, Santos, K., Capella, C., Duke, C.M.P., and Dewhurst, S. In vivo gene delivery and expression by bacteriophage lambda vectors. J. Appl. Microbiol. 102:1337-1349, 2007. *: Co-First Authors.
Santos, K.*, Simon, D.A.L.*, Conway, E., Bowers, W.J., Mitra, S., Foster, T.H., Lugade, A., Lord, E., Federoff, H.J., Dewhurst, S., and Frelinger, J.G. Spatial and temporal expression of HSV-1 amplicon encoded genes: implications for their use as immunization vectors. Hum. Gene Ther. 18(2):1-13, 2007. *: Co-First Authors.
Sui, Z., Sniderhan, L., Schifitto, G., Phipps, R.P., Gelbard, H.A., Dewhurst, S., Maggirwar, S.B. Functional synergy between CD40L and HIV-1 Tat contributes to inflammation: implications in HIV-1 dementia. J. Immunol. 178:3226-3236, 2007.
Zanghi, C.N., Sapinoro, R., Bradel-Tretheway, B., Dewhurst, S. A tractable method for simultaneous modifications to the head and tail of bacteriophage lambda and its application to enhancing phage mediated gene delivery. Nuc. Acids Res. 37: e59, 2007.
Malboeuf, C.M., Simon, D.A.L., Lee, Y.E., Lankes, H., Dewhurst, S. Frelinger, J.G., Rose, R.C. Human papillomavirus-like particles mediate functional delivery of plasmid DNA to antigen-presenting cells in vivo. Vaccine 25:3270-6, 2007.
Santos, K.*, Sanfilippo, C.M.*, Narrow, W.C., Casey, A.E., Rodrigez-Colon, S.M. McDermott, M.P., Federoff, H.J., Bowers, W.J., Dewhurst, S. Infectivity of Herpes Simplex Virus Type-1 (HSV-1) amplicon vectors in dendritic cells is determined by the helper virus strain used for packaging. J. Virol. Methods 145:37-46, 2007. *: Co-First Authors.
Duke, C., Maguire, C.A., Keefer, M.C., Federoff, H.J., Bowers, W.J., Dewhurst, S. HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime. Vaccine 25:7410-21, 2007.
Sapinoro, R., Maguire, C.A., Burgess, A., Dewhurst, S. Enhanced transduction of dendritic cells by FcgRI-targeted adenovirus vectors. J. Gene Med. 9:1033-45, 2007.
Chugh, P., Bradel-Tretheway, B., Monteiro-Filho, C.M.R., Planelles, V., Maggirwar, S.B., Dewhurst S., Kim, B. Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy. Retrovirology 5:11, 2008.
Sapinoro, R., Volcy, K., Rodrigo, W.W.S.I., Schlesinger, J.J., Dewhurst S. Fc receptor mediated, antibody-dependent enhancement of bacteriophage lambda-mediated gene transfer in mammalian cells. Virology 373:274-286, 2008.

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