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; Gene transfer studies; Therapeutic approaches to neuroAIDS
Research Overview
HIV Vaccine Development: We are examining novel methods for the delivery of vaccines for HIV/AIDS. Ongoing studies include experiments designed to optimize the efficacy of replication-defective herpesvirus vector systems (HSV amplicon vectors) in mice, as well as exploratory studies aimed at the development of novel bacteriophage lambda vectors that can express candidate vaccine proteins in antigen-presenting cells. Collaborators include Howard Federoff, Bill Bowers, Mike Keefer, John Frelinger, Tim Mosmann, Xia Jin and others.
Gene transfer studies: Adenovirus vectors that replicate selectively in tumor cells are being developed for the treatment of human cancers. One such product was recently licensed in China. We are testing whether one can create improved, conditionally replicating adenoviruses, capable of replicating only in cancer cells that contain high amounts of DNA building blocks (dNTPs). Other studies are focused on using gene transfer approaches for the treatment of irradiation-induced dry mouth (xerostomia), which is a frequent and serious complication of treatment for head-and-neck cancers. Collaborators include Baek Kim, Jim Melvin, Rob Quivey and others.
Therapeutic Approaches to NeuroAIDS: HIV-1 causes motor and cognitive deficits which are thought to be due to the production of neurotoxic effector molecules by virally-infected and/or activated microglia and brain-resident macrophages. Importantly, the incidence of neuroAIDS continues to grow, even in the post-HAART era. Thus, we are interested in identifying molecular pathways which contribute to neuronal disfunction and damage in neuroAIDS. Ongoing studies focus on mechanisms that modulate microglial/macrophage activation, and neuroprotection. Collaborators include Handy Gelbard, Sanjay Maggirwar, Giovanni Schifitto and others.
Recent Publications
Sapinoro R, Volcy K, Rodrigo WW, Schlesinger JJ, Dewhurst S. Fc receptor-mediated, antibody-dependent enhancement of bacteriophage lambda-mediated gene transfer in mammalian cells. Virology. 2008 Apr 10;373(2):274-86
Sapinoro R, Maguire CA, Burgess A, Dewhurst S Enhanced transduction of dendritic cells by FcgammaRI-targeted adenovirus vectors. J Gene Med. 2007 Dec;9(12):1033-45
Chugh P, Bradel-Tretheway B, Monteiro-Filho CM, Planelles V, Maggirwar SB, Dewhurst S, Kim B Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy. Retrovirology. 2008;5:11
Sapinoro R, Volcy K, Rodrigo WW, Schlesinger JJ, Dewhurst S " Fc receptor-mediated, antibody-dependent enhancement of bacteriophage lambda-mediated gene transfer in mammalian cells." Virology. 2008 Jan 11;
Dewhurst S, Maggirwar SB, Schifitto G, Gendelman HE, Gelbard HA "Glycogen synthase kinase 3 Beta (GSK-3beta) as a therapeutic target in neuroAIDS." J Neuroimmune Pharmacol. 2007 Mar;2(1):93-6
Sapinoro R, Maguire CA, Burgess A, Dewhurst S "Enhanced transduction of dendritic cells by FcgammaRI-targeted adenovirus vectors" J Gene Med. 2007 Oct 26; [Epub ahead of print]
Duke CM, Maguire CA, Keefer MC, Federoff HJ, Bowers WJ, Dewhurst S "HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime." Vaccine. 2007 Aug 30;
Santos K, Sanfilippo CM, Narrow WC, Casey AE, Rodriguez-Colon SM, McDermott MP, Federoff HJ, Bowers WJ, 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. 2007 Jun 30;
Lankes HA, Zanghi CN, Santos K, Capella C, Duke CM, Dewhurst S "In vivo gene delivery and expression by bacteriophage lambda vectors." J Appl Microbiol. 2007 May;102(5):1337-49
Santos K, Simon DA, Conway E, Bowers WJ, Mitra S, Foster TH, Lugade A, Lord EM, Federoff HJ, Dewhurst S, Frelinger JG. "Spatial and temporal expression of herpes simplex virus type 1 amplicon-encoded genes: implications for their use as immunization vectors." Hum Gene Ther. 2007 Feb;18(2):1-13.
Malboeuf CM, Simon DA, Lee YE, Lankes HA, Dewhurst S, Frelinger JG, Rose RC. "Human papillomavirus-like particles mediate functional delivery of plasmid DNA to antigen presenting cells in vivo." Vaccine. 2007 Jan 22;
Gorantla S, Sneller H, Walters L, Sharp JG, Pirruccello SJ, West JT, Wood C, Dewhurst S, Gendelman HE, Poluektova L. "HIV-1 pathobiology studied in humanized Balb/c-Rag2-/-{gamma}c-/- mice." J Virol. 2006 Dec 20;
Santos K, Duke CM, Rodriguez-Colon SM, Dakwar A, Fan S, Keefer MC, Federoff HJ, Frelinger JG, Bowers WJ, Dewhurst S "Effect of promoter strength on protein expression and immunogenicity of an HSV-1 amplicon vector encoding HIV-1 Gag." Vaccine. 2006 Nov 15;
Chugh P, Fan S, Planelles V, Maggirwar SB, Dewhurst S, 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. 2006 Nov 10;
Sui Z, Fan S, Sniderhan L, Reisinger E, Litzburg A, Schifitto G, Gelbard HA, Dewhurst S, Maggirwar SB "Inhibition of mixed lineage kinase 3 prevents HIV-1 Tat-mediated neurotoxicity and monocyte activation." J Immunol. 2006 Jul 1;177(1):702-11
Sui Z, Sniderhan LF, Fan S, Kazmierczak K, Reisinger E, Kovács AD, Potash MJ, Dewhurst S, Gelbard HA, Maggirwar SB "Human immunodeficiency virus-encoded Tat activates glycogen synthase kinase-3beta to antagonize nuclear factor-kappaB survival pathway in neurons." Eur J Neurosci. 2006 May;23(10):2623-34
Santos K, Duke CM, Dewhurst S "Amplicons as vaccine vectors" Curr Gene Ther. 2006 Jun;6(3):383-92
Hall CB, Caserta MT, Schnabel KC, McDermott MP, Lofthus GK, Carnahan JA, Gilbert LM, Dewhurst S. Characteristics and Acquisition of Human Herpesvirus (HHV) 7 Infections in Relation to Infection with HHV-6. J Infect Dis. 193(8):1063-9, 2006.
Maguire CA, Sapinoro R, Girgis N, Rodriguez-Colon SM, Ramirez SH, Williams J, Dewhurst S. ' Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and alpha(v)beta3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens. Vaccine 24(5):671-82, 2006.
Zanghi CN, Lankes HA, Bradel-Tretheway B, Wegman J, Dewhurst S. A simple method for displaying recalcitrant proteins on the surface of bacteriophage lambda. Nucleic Acids Res. 33(18):e160, 2005.
Dou H, Ellison B, Bradley J, Kasiyanov A, Poluektova LY, Xiong H, Maggirwar S, Dewhurst S, Gelbard HA, Gendelman HE. Neuroprotective mechanisms of lithium in murine human immunodeficiency virus-1 encephalitis. J Neurosci. 25(37):8375-85, 2005.
Zhen Z, Bradel-Tretheway B, Sumagin S, Bidlack JM, Dewhurst S. The human herpesvirus 6 G protein-coupled receptor homolog U51 positively regulates virus replication and enhances cell-cell fusion in vitro. J Virol. 79(18):11914-24, 2005.
Perry SW, Norman JP, Litzburg A, Zhang D, Dewhurst S, Gelbard HA. HIV-1 transactivator of transcription protein induces mitochondrial hyperpolarization and synaptic stress leading to apoptosis. J Immunol. 2005 Apr 1;174(7):4333-44.
Fan S, Maguire CA, Ramirez SH, Bradel-Tretheway B, Sapinoro R, Sui Z, Chakraborty-Sett S, Dewhurst S. Valproic acid enhances gene expression from viral gene transfer vectors. J Virol Methods. 2005 Apr;125(1):23-33.
Gorantla S, Santos K, Meyer V, Dewhurst S, Bowers WJ, Federoff HJ, Gendelman HE, Poluektova L. Human dendritic cells transduced with herpes simplex virus amplicons encoding human immunodeficiency virus type 1 (HIV-1) gp120 elicit adaptive immune responses from human cells engrafted into NOD/SCID mice and confer partial protection against HIV-1 challenge. J Virol. 2005 Feb;79(4):2124-32.
Renda MJ, Bradel-Tretheway B, Planelles V, Bambara RA, Dewhurst S. Inhibition of HIV Type 1 Replication Using Lentiviral-Mediated Delivery of Mutant tRNA(Lys3)A58U. AIDS Res Hum Retroviruses. 20:1324-34, 2004.
Fan S, Ramirez SH, Garcia TM, Dewhurst S. Dishevelled promotes neurite outgrowth in neuronal differentiating neuroblastoma 2A cells, via a DIX-domain dependent pathway. Brain Res Mol Brain Res. 132:38-50, 2004.
Caserta MT, McDermott MP, Dewhurst S, Schnabel K, Carnahan JA, Gilbert L, Lathan G, Lofthus GK, Hall CB. Human herpesvirus 6 (HHV6) DNA persistence and reactivation in healthy children. J Pediatr. 145:478-84, 2004.
Hall CB, Caserta MT, Schnabel KC, Boettrich C, McDermott MP, Lofthus GK, Carnahan JA, Dewhurst S. Congenital infections with human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7). J Pediatr. 2004 Oct;145(4):472-7.
Diamond TL, Roshal M, Jamburuthugoda VK, Reynolds HM, Merriam AR, Lee KY, Balakrishnan M, Bambara RA, Planelles V, Dewhurst S, Kim B. Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase. J Biol Chem. 279:51545-53, 2004
Ramirez SH, Fan S, Maguire CA, Perry S, Hardiek K, Ramkumar V, Gelbard HA, Dewhurst S, Maggirwar SB. Activation of adenosine A2A receptor protects sympathetic neurons against nerve growth factor withdrawal. J Neurosci Res. 77:258-69, 2004.
Zhen Z, Bradel-Tretheway BG, Dewhurst S, Bidlack JM. Transient overexpression of kappa and mu opioid receptors using recombinant adenovirus vectors. J Neurosci Methods 136:133-9, 2004.
Latchney LR, Fallon MA, Culp DJ, Gelbard HA, Dewhurst S. Immunohistochemical Assessment of Fractalkine, Inflammatory Cells, and Human Herpesvirus 7 in Human Salivary Glands. J Histochem Cytochem. 52:671-682, 2004.
Dou H, Birusingh K, Faraci J, Gorantla S, Poluektova LY, Maggirwar SB, Dewhurst S, Gelbard HA, Gendelman HE. Neuroprotective activities of sodium valproate in a murine model of human immunodeficiency virus-1 encephalitis. J Neurosci. 23:9162-70, 2003.
Diamond TL, Souroullas G, Weiss KK, Lee KY, Bambara RA, Dewhurst S, Kim B. Mechanistic understanding of an altered fidelity simian immunodeficiency virus reverse transcriptase mutation, V148I, identified in a pig-tailed macaque J Biol Chem. 278:29913-24, 2003.
Bradel-Tretheway BG, Zhen Z, Dewhurst S. Effects of codon-optimization on protein expression by the human herpesvirus 6 and 7 U51 open reading frame. J Virol Methods 111:145-56, 2003.
Wang X, Messerle M, Sapinoro R, Santos K, Hocknell PK, Jin X, Dewhurst S. Murine cytomegalovirus abortively infects human dendritic cells, leading to expression and presentation of virally vectored genes J. Virol. 77:7182-7192, 2003.
Wang X, Wiley RD, Evans TG, Bowers WJ, Federoff HJ, Dewhurst S. Cellular immune responses to helper-free HSV-1 amplicon particles encoding HIV-1 gp120 are enhanced by DNA priming. Vaccine 21:2288-2297, 2003
Selected Review Articles
Dewhurst S. Human herpesvirus type 6 and human herpesvirus type 7 infections of the central nervous system. Herpes. 2004 Jun;11 Suppl 2:105A-111A. Review.
Perry SW, Dewhurst S, Bellizzi MJ, Gelbard HA. Tumor necrosis factor-alpha in normal and diseased brain: Conflicting effects via intraneuronal receptor crosstalk? J Neurovirol. 8:611-24, 2002.
Caserta MT, Mock DJ, Dewhurst S. Human herpesvirus 6. Clin. Infect. Dis. 33:829-833, 2001.
Dewhurst SL, da Cruz RL, Whetter L. Pathogenesis and treatment of HIV-1 infection: recent developments (Y2K update). Front Biosci. 5:D30-49, 2000.

Publication list, as provided by PubMed.
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