IN MEMORIUM
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William Edward Robinson


Professor, Pathology
School of Medicine
Professor, Microbiology & Molecular Genetics
School of Medicine
Professor, Medicine
School of Medicine

M.D., Vanderbilt University
PH.D., Vanderbilt University

Phone: (949) 824-3431
Fax: (949) 824-2505
Email: ewrobins@uci.edu

University of California, Irvine
D440 Medical Sciences I
Mail Code: 4800
Irvine, CA 92697-480
Research Interests
HIV, SIV, Integrase, Virology, Pathogenesis, AIDS, Drug discovery, Therapeutics
URL
Academic Distinctions
Burroughs Wellcome Clinical Scientist in Translational
Research
Research Abstract
The human immunodeficiency virus (HIV) is the causative agent in the acquired immune deficiency syndrome (AIDS). Working with organic chemists, we are developing novel anti-HIV agents for use in combination therapy for the treatment of AIDS. These inhibitors act at a unique site in the viral lifecycle: integration. Integration of the virus is absolutely required for efficient and stable infection. Using such inhibitors, we are isolating drug-resistant variants of HIV integrase to better understand the molecular mechanisms of HIV integration. Through the rational design of new inhibitors of integrase, we believe we will identify novel compounds for the prevention of AIDS. Recent work from the laboratory demonstrates that integrase inhibitors work effectively in combination with existing anti-HIV agents including both protease and reverse transcriptase inhibitors. These molecules also work against HIV that is resistant to both protease and reverse transcriptase inhibitors. Therefore, the goals of the laboratory are 1) to study and ultimately understand the mechanism of retroviral integration; 2) to understand the mechanism of action of and mechanism of drug resistance to integrase inhibitors; 3) using this information design and synthesize novel anti-HIV agents for potential clinical use.
Publications
Peterson, M., Ke, P., Shi, H., Jones, C., McDougall, B.R., and Robinson, W.E., Jr. Design, synthesis and antiviral evaluation of some 3'-carboxymethyl-3'-deoxyadenosine derivatives. Nucleosides, Nucleotides, and Nucleic Acids. 26:499-519 (2007).
 
Robinson, W.E., Jr. Mechanism for complement-mediated, antibody-dependent enhancement of human immunodeficiency virus type 1 infection in MT2 cells is enhanced entry through CD4, CD21, and CXCR4 chemokine receptors. Viral Immunol. 19:434-447 (2006)
 
Charvat, T.T., Lee, D.J., Robinson, W.E., Jr., and Chamberlin, A.R. Design, synthesis, and biological evaluation of chicoric acid analogs as inhibitors of HIV-1 integrase. Bioorg. Med. Chem. 14:4552-4567 (2006).
 
Lee, D.J. and Robinson, W.E., Jr. Preliminary mapping of a putative inhibitor binding pocket for human immunodeficiency virus type 1 integrase inhibitors. Antimicrob. Agents Chemother. 50:134-142 (2006).
 
Victoria, J.G. and Robinson, W.E., Jr. Disruption of the putative splice acceptor site for SIVmac239 vif reveals tight control of SIV splicing and impaired replication in Vif non-permissive cells. Virology: In press, published online doi:10.1016/j.virol.2005.05.007. (2005).
 
Kuznetsov, Y.G., Victoria, J.G., Low, A., Robinson, W.E., Jr., Fan, H., McPherson, A. Atomic force microscopy imaging of retroviruses: human immunodeficiency virus and murine leukemia virus. Scanning 26:209-216 (2004).
 
Tanabe, H., Ouellette, A., Cocco, M.J., and Robinson, W.E., Jr. Differential effects on human immunodeficiency virus type 1 replication by a-defensins of comparable bactericidal activities. J. Virol. 78:11622-11631 (2004).
 
Olszewski, A., Sato, K., Aron, Z.D., Cohen, F., Harris, A., McDougall, B.R., Robinson, W.E., Jr., Overman, L.E., and Weiss, G.A. Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck. Proc. Natl. Acad. Sci., USA 101:14079-14084 (2004).
 
Tanabe, H., Ouellette, A., Cocco, M.J., and Robinson, W.E., Jr. Differential effects on human immunodeficiency virus type 1 replication by a-defensins of comparable bactericidal activities. J. Virol. in press, (2004).
 
Reinke, R.A., Lee, D.J., McDougall, B.R., King, P.J., Victoria, J., Mao, Y., Lei, X., Reinecke, M.G., and Robinson, W.E., Jr. L-chicoric acid inhibits human immunodeficiency virus type 1 (HIV-1) integration in vivo and is a non-competitive but reversible inhibitor of HIV-1 integrase in vitro. Virology 326:203-219, (2004).
 
Lee, D.J. and Robinson, W.E., Jr. Human immunodeficiency virus type 1 (HIV-1) integrase: resistance to diketoacid integrase inhibitors impairs HIV-1 replication, integration, and confers cross-resistance to L-chicoric acid. J. Virol. 78:5835-5847 (2004).
 
Kuznetsov, Y.G., Victoria, J., Robinson, W.E., Jr., and McPherson, A. Atomic force microscopy investigation of HIV and HIV-infected lymphocytes. J. Virol. 77:11896-11909 (2003).
 
Victoria, J.G., Lee, D.J., McDougall, B.R., and Robinson, W.E., Jr. Replication kinetics for divergent type 1 human immunodeficiency viruses using quantitative SYBR green I real-time polymerase chain reaction. AIDS Res. Human Retroviruses 19:865-874 (2003).
 
King, P.J. Lee, D.J., Reinke, R.A., Victoria, J.G., Beale, K.K., and Robinson, W.E., Jr. Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. Virology 306:146-161 (2003).
 
Reinke, R.A., Lee, D.J., and Robinson, W.E., Jr. Inhibition of human immunodeficiency virus type 1 isolates by the integrase inhibitor, L-731,988, a diketo acid. Antimicrob. Agents Chemother. 46:3301-3303 (2002).
 
Reinke, R.A., King, P.J., Victoria, J.G., McDougall, B.R., Ma, G., Mao, Y., Reinecke, M.G., and Robinson, W.E., Jr. Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at non-toxic concentrations. J. Med. Chem. 45:3669-3683 (2002).
Professional Societies
American Society of Microbiology
American Society of Biochemistry and Molecular Biology
International AIDS Society
Graduate Programs
Virology

Immunology and Pathogenesis

Cellular and Molecular Biosciences

Research Centers
Cancer Research Institute
Center for Virus Research
Center for Immunology
Last updated
01/07/2008