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Secondary Faculty profile

Robert Siliciano Photo

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Robert Siliciano - Professor
Howard Hughes Medical Institute and Department of Medicine

Edward D. Miller Research Building
733 N. Broadway, Room 879
Baltimore, MD 21205

Office: 410-955-2958
Fax: 443-287-6218

rsiliciano@jhmi.edu

Assistant:
Host-virus interaction in HIV infection
     For the 34 million people infected with HIV-1, the best current hope for avoiding the fatal consequences of the infection lies in treatment with antiretroviral therapy (ART), which consists of combinations of three drugs that inhibit specific steps in the virus life cycle.  The benefits of ART in reducing the morbidity and mortality are clear, but ART is not curative.  In 1995, our laboratory provided the first demonstration that latently infected CD4+ T cells were present in patients with HIV-1 infection.  We later found that latently infected cells persist indefinitely even in patient on prolonged ART.  These studies indicated that eradication of HIV-1 infection with ART alone would never be possible.   The latent reservoir for HIV-1 in resting CD4+ T cells is now widely recognized as the major barrier to curing HIV-1 infection and is the subject of an intense international research effort.  Our laboratory has gone on to characterize the different forms of HIV-1 that persist in patients on ART and to explore potential strategies for eradicating the virus.   In particular, we are searching for and evaluating drugs that target the latent reservoir.  We are also developing assays that can be used to monitor the elimination of this reservoir in patients participating in eradication trials.  The laboratory is also interested in the basic pharmacodynamic principles that explain how antiretroviral drugs work.  We have recently uncovered a previously unrecognized form of intermolecular cooperatively that explains why certain classes of antiretroviral drugs are so effective at inhibiting viral replication.  We are using this discovery along with experimental and computational approaches to develop improved therapies for HIV-1 infection and to understand and prevent drug resistance.  Finally we are studying the immunology of HIV-1 infection, and in particular, the ability of some patients to control the infection without ART.

Relevant Publications:

Ho, Y.C., Shan, L., Hosmanie, N.N., Wang, J., Laskey, S.B., Rosenbloom, D.I., Lai, J., Blankson, J.N., Siliciano, J.D., and Siliciano, R.F. (2013). Replication-competent non-induced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell   In press.

Rabi, S.A., Laird, G.M., Durand, C.M., Laskey, S., Shan, L., Bailey, J.R., Chioma, S., Moore, R.D., and Siliciano, R.F. (2013). Multi-step inhibition explains HIV-1 protease inhibitor pharmacodynamics and resistance. J. Clin. Invest. In press.
 
Eriksson, S., Graf, E.H., Dahl, V., Strain, M.C., Yukl, S.A., Lysenko, E.S., Bosch, R.J., Lai, J., Chioma, S., Emad, F., et al. (2013). Comparative Analysis of Measures of Viral Reservoirs in HIV-1 Eradication Studies. PLoS Pathog. 9, e1003174. PubMed

Goldberg, D.E., Siliciano, R.F., and Jacobs, W.R.,Jr. (2012). Outwitting Evolution: Fighting Drug-Resistant TB, Malaria, and HIV. Cell 148, 1271-1283. PubMed

Jilek, B.L., Zarr, M., Sampah, M.E., Rabi, S.A., Bullen, C.K., Lai, J., Shen, L., and Siliciano, R.F. (2012). A quantitative basis for antiretroviral therapy for HIV-1 infection. Nat. Med. 18, 446-451. PubMed

Laird, G.M., Eisele, E.E., Rabi, S.A., Lai, J., Chioma, S., Blankson, J.N., Siliciano, J.D., and Siliciano, R.F. (2013). Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay. PLoS Pathog. 9, e1003398. PubMed
 
Rosenbloom, D.I., Hill, A.L., Rabi, S.A., Siliciano, R.F., and Nowak, M.A. (2012). Antiretroviral dynamics determines HIV evolution and predicts therapy outcome. Nat. Med. 18, 1378-1385. PubMed
 
Shan, L., Deng, K., Shroff, N.S., Durand, C.M., Rabi, S.A., Yang, H.C., Zhang, H., Margolick, J.B., Blankson, J.N., and Siliciano, R.F. (2012). Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36, 491-501. PubMed

Sampah, M.E., Shen, L., Jilek, B.L., and Siliciano, R.F. (2011). Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance. Proc. Natl. Acad. Sci. U. S. A. 108, 7613-7618. PubMed

Shen, L., Rabi, S.A., Sedaghat, A.R., Shan, L., Lai, J., Xing, S., and Siliciano, R.F. (2011). A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs. Sci. Transl. Med. 3, 91ra63. PubMed
Graduate Program AffiliationsBiochemistry, Cellular & Molecular Biology (BCMB)

 

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