Dr. Dewhurst is Dean's Professor and Chair of Microbiology & Immunology at the University of Rochester School of Medicine and Dentistry (URSMD). He received his Ph.D. from the University of Nebraska Medical Center in 1987, and performed postdoctoral training at Columbia University and at the Harvard School of Public Health, under the direction of Dr. Jim Mullins. His doctoral and postdoctoral work focussed on the pathogenesis of human and simian immunodeficiency viruses. He has been a member of the faculty at the University of Rochester since 1990, and served as Senior Associate Dean for Basic Research at the URSMD from 2007 to 2009.
He has over 20 years experience as a molecular virologist, working on both RNA and DNA viruses (including HIV-1 and human herpesviruses) and is expert in the areas of viral gene transfer vectors, HIV-1 vaccine development and neuroAIDS. He has served on many NIH special emphasis and regular grant review panels and is a former Study Section Chair as well as a past (2004-2008) member of the NIH Recombinant Advisory Committee (RAC), which oversees all recombinant DNA studies in human subjects. He serves as Director of the UR's NIH-funded Development Center for AIDS Research, and also directs a NIH-funded Predoctoral training program in HIV-1 research, in addition to his own research.
Current research interests in our laboratory include the following:
HIV VACCINE AND MICROBICIDE DEVELOPMENT: An effective HIV vaccine must elicit protective immune responses at mucosal sites of virus transmission. It is thought that mucosal delivery of vaccines may hold the key to this. We are therefore exploring whether this problem can be solved by delivering nanoparticle based vaccines by a mucosal route, under the tongue. This "sublingual" route of delivery has been safely used to deliver medicines such as nitroglycerin for decades, but has been little studied in the setting of vaccine administration.
Improving the mucosal immune response is only part of the battle, in terms of developing a successful HIV vaccine. Also needed are improved immunogens, capable of evoking virus neutralizing antibodies that recognize diverse virus strains. However, antibodies of this kind have proven hard to generate, in part because the virus structures that they recognize are normally hidden from the immune system. We are therefore also working to develop improved vaccine immunogens, by producing novel "antigenic mimics" of key structures present on the surface of the virus.
Finally, we are also exploring new approaches to microbicide development, by targeting amyloid structures in semen, known as SEVI. SEVI enhances infection by allowing HIV particles to stick more efficiently to the immune cells that the virus infects. We are presently examining the normal function of SEVI, which presumably did not evolve to enhance HIV infection! We are also developing novel developing compounds that prevent SEVI from interacting with the virus – thereby reducing the efficiency of HIV infection. This strategy is different from most other antiviral approaches, because it targets an invariant host factor – making it very unlikely that the virus could ever become resistant to SEVI inhibitors.
NEUROAIDS RESEARCH: NOVEL THERAPEUTICS and STUDIES OF CEREBRAL BLOOD FLOW: HIV-Associated Neurocognitive Disorders (HAND) continue to affect more than 50% of persons living with HIV, despite the widespread use of effective antiviral drugs. This suggests that chronic, virally-initiated, neuroinflammation may persist over time – leading to neuronal disfunction and damage. In collaboration with Handy Gelbard, we are therefore working to develop new therapies for HAND, by targeting mixed lineage kinase (MLK)-3, an upstream kinase involved in the regulation of neuroinflammation and cell fate. In separate studies, we are also examining the mechanisms by which HIV infection leads to inhibition of cerebral blood flow (CBF). These experiments include an analysis of how virally-encoded neurotoxins may interact with drugs of abuse (such as methamphetamine) to exacerbate CNS disease and neuroinflammation.
ROLE OF CELLULAR FACTORS IN INFLUENZA VIRUS PATHOGENESIS AND HOST ADAPTATION: The influenza A virus (IAV) RNA polymerase complex is known to play an important role in viral pathogenesis and host adaptation, but the underlying reasons for this remain unclear. In collaboration with the Katze laboratory at the University of Washington, our group recently completed an extensive proteomic analysis of host cell factors that interact with the IAV RNA polymerase. This resulted in the identification of large number of mitochondrial proteins, and other cellular proteins that were previously not recognized to play a role in influenza virus infection. Current studies in our laboratory are examining how these proteins influence virus replication, and pathogenesis, as well as the activity of the viral RNA polymerase.
High Affinity Binding Proteins to Integrins|
United States Serial NO.: 10/473,770
Filed Date: April 4, 2002
Title: avB3 Integrin-Binding Polypeptide Monobodies and Their Use
Invented by: Shohei Koide, Stephen Dewhurst, Akiko Koide, Julie Richards Gunzler, Michelle Miller
Glycoprotein Decoration of Lambda Phage Particles: Application to Vaccine Development for Influenza Virus and Other Indications|
United States Serial NO.: 12/514,903
Filed Date: November 20, 2007
Title: Modified Phage for Displaying Post-Translationally Modified Proteins and Uses Thereof
Invented by: Stephen Dewhurst, John Treanor
Antigenic Mimics of Discontinuous HIV-1 Envelope Epitopes Recognized by Broadly Neutralizing Antibodies|
United States Serial NO.: 13/577,419
Filed Date: February 14, 2011
Title: Antigenic Mimics of Discontinuous Epitopes of Pathogens Recognized by Broadly Neutralizing Antibodies
Invented by: Stephen Dewhurst, Mark Sullivan
Novel Inhibitors of SEVI-Mediated Enhancement of HIV Infection|
United States Serial NO.: 14/357,037
Filed Date: November 8, 2012
Title: Reducing Transmission of Sexually Transmitted Infections
Invented by: Jerry Yang, Stephen Dewhurst, Christina Capule
A Selectively Non-Selective Mixed Lineage Kinase 3 Inhibitor Potentiates the Effectiveness of Antiretroviral Therapy for HIV/AIDS|
United States Serial NO.:
Filed Date: November 30, 2013
Title: MIxed Lineage Kinase Inhibitors for HIV/AIDS Therapies
Invented by: Harris Gelbard, Stephen Dewhurst, Howard Gendelman
Silva JN, Polesskaya O, Wei HS, Rasheed IY, Chamberlain JM, Nishimura C, Feng C, Dewhurst S. "Chronic central nervous system expression of HIV-1 Tat leads to accelerated rarefaction of neocortical capillaries and loss of red blood cell velocity heterogeneity." Microcirculation : the official journal of the Microcirculatory Society, Inc. 2014 Oct; 21(7):664-76.
Nogales A, Baker SF, Ortiz-Riaño E, Dewhurst S, Topham DJ, Martínez-Sobrido L. "Influenza A virus attenuation by codon deoptimization of the NS gene for vaccine development." Journal of virology. 2014 Sep; 88(18):10525-40. Epub 2014 Jun 25.
Polesskaya O, Wong C, Lebron L, Chamberlain JM, Gelbard HA, Goodfellow V, Kim M, Daiss JL, Dewhurst S. "MLK3 regulates fMLP-stimulated neutrophil motility." Molecular immunology. 2014 Apr; 58(2):214-22. Epub 2014 Jan 03.
Domm W, Brewer M, Baker SF, Feng C, Martínez-Sobrido L, Treanor J, Dewhurst S. "Use of bacteriophage particles displaying influenza virus hemagglutinin for the detection of hemagglutination-inhibition antibodies." Journal of virological methods. 2014 Mar; 197:47-50. Epub 2013 Dec 06.
Lewis CA, Dewhurst S, McMahon JM, Bunce CA, Keefer MC, Alio AP. "Theoretical model of critical issues in informed consent in HIV vaccine trials." AIDS care. 2014 26(11):1452-60. Epub 2014 May 28.