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Department Affiliation: Primary: Howard Hughes Medical Institute and Department of Medicine; Secondary: Molecular Biology and Genetics, Pharmacology and Molecular Sciences, and Biology (Arts and Sciences)
Degree: M.D., Ph.D., Johns Hopkins University
Telephone Number: 410-955-2958
Fax Number: 443-287-6218
E-mail address: firstname.lastname@example.org
School of Medicine Address: Room 879, Edward D. Miller Research Building, 733 N. Broadway, Baltimore, MD 21205
Drug therapy for 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 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 patients 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.
Ho, Y.C., Shan, L., Hosmanie, N.N., Wang, J., Laskey, S.B., Rosenbloom, D.I., Lai, J., Blankson, J.N., Siliciano, J.D., 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., Siliciano, R.F. (2013). Multi-step inhibition explains HIV-1 protease inhibitor pharmacodynamics and resistence. J. Clin. Invest. In press. Pub Med Reference
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. Pub Med Reference
Goldberg, D.E., Siliciano, R.F., Jacobs, W.R. Jr. (2012). Outwitting evolution: fighting drug-resistant TB, malaria, and HIV. Cell 148, 1271-1283. Pub Med Reference
Jilek, B.L., Zarr, M., Sampah, M.E., Rabi, S.A., Bullen, C.K., Lai, J., Shen, L., Siliciano, R.F. (2012). A quantitative basis for antiretroviral therapy for HIV-1 infection. Nat. Med. 18, 446-451. Pub Med Reference
- Laird, G.M., Eisele, E.E., Rabi, S.A., Lai, J., Chioma, S., Blankson, J.N., Siliciano, J.D., Siliciano, R.F. (2013). Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay. PLoS Pathog. 9, e1003398. Pub Med Reference
- Rosenbloom, D.I., Hill, A.L., Rabi, S.A., Siliciano, R.F., Nowak, M.A. (2012). Antiretroviral dynamics determines HIV evolution and predicts therapy outcome. Nat. Med. 18, 1378-1385. Pub Med Reference
- Shan, L., Deng, K., Shroff, N.S., Durand, C.M., Rabi, S.A., Yang, H.C., Zhang, H., Margolick, J.B., Blankson, J.N., Siliciano, R.F. (2012). Stimulation of HIV-1-specific cytoytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36, 491-501. Pub Med Reference
- Sampah, M.E., Shen, L., Jilek, B.L., Siliciano, R.F. (2011). Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance. Proc. Natl. Acad. Sci. USA 108, 7613-7618. Pub Med Reference
- Shen, L., Rabi, S.A., Sedaghat, A.R., Shan, L., Lai, J., Xing, S., 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. Pub Med Reference
Other graduate programs in which Dr. Siliciano participates: