Joel N. Blankson, MD, PhD

Primary Academic Title

Professor of Medicine

Background

Additional Academic Titles

Professor of Molecular and Comparative Pathobiology

Contact for Research Inquiries

733 North Broadway, Suite 147
833 Miller Research Building
Baltimore, MD 21205-2196

Research Interests

Natural Control of HIV-1 Infection

Lab Website

Joel Blankson Lab

• Work in the Joel Blankson Lab explores the mechanism of control of HIV-1 replication in a cohort of patients known as elite controllers or elite suppressors. These patients are HIV-1 seropositive but maintain levels of viremia that are below the limit of detection of standard clinical assays. We feel that elite suppressors represent a potential model for a therapeutic HIV vaccine. Our central hypothesis is that many of these patients are infected with fully replication-competent HIV-1 isolates that are held in check by the immune system. To test this hypothesis, we are studying many different host and viral factors in these patients.

Research Summary

Dr. Blankson’s laboratory has focused on the mechanism of control of HIV-1 replication in a cohort of patients known as elite controllers or elite suppressors. These patients are HIV-1 seropositive, but maintain levels of viremia that are below the limit of detection of standard clinical assays. Dr. Blankson and his team feel that elite suppressors represent a potential model for a therapeutic HIV vaccine. Their central hypothesis is that many of these patients are infected with fully replication-competent HIV-1 isolates that are held in check by the immune system. To test this hypothesis, they are studying many different host and viral factors in these patients.

They have shown that CD4+ T cells from these patients are not intrinsically resistant to HIV-1 infection and that elite control is probably not due to HIV-specific neutralizing antibody or NK cell responses. While HIV-specific CTL responses are known to be important in controlling viral replication, they have shown that virus amplified from these patients have developed escape mutations in immunodominant epitopes. They are thus trying to determine how control of viral replication is maintained in the presence of immunologic escape.

Selected Publications

• Blankson JN. Killing the messenger to maintain control of HIV. Nat Med. 2011 Aug 4;17(8):927-8. doi: 10.1038/nm.2427. PubMed PMID: 21818087.

• Buckheit RW 3rd, Allen TG, Alme A, Salgado M, O'Connell KA, Huculak S, Falade-Nwulia O, Williams TM, Gallant JE, Siliciano RF, Blankson JN. Host factors dictate control of viral replication in two HIV-1 controller/chronic progressor transmission pairs. Nat Commun. 2012 Mar 6;3:716. doi: 10.1038/ncomms1697. PubMed PMID: 22395607; PubMed Central PMCID: PMC3549550.

• Buckheit RW 3rd, Salgado M, Martins KO, Blankson JN. The implications of viral reservoirs on the elite control of HIV-1 infection. Cell Mol Life Sci. 2013 Mar;70(6):1009-19. doi: 10.1007/s00018-012-1101-7. Epub 2012 Aug 4. Review.PubMed PMID: 22864624.

• Buckheit RW 3rd, Salgado M, Silciano RF, Blankson JN. Inhibitory potential of subpopulations of CD8+ T cells in HIV-1-infected elite suppressors. J Virol. 2012 Dec;86(24):13679-88. doi: 10.1128/JVI.02439-12. Epub 2012 Oct 10. PubMed PMID:23055552; PubMed Central PMCID: PMC3503034.

• Buckheit RW 3rd, Siliciano RF, Blankson JN. Primary CD8+ T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4+ T cells. Retrovirology. 2013 Jul 1;10:68. doi: 10.1186/1742-4690-10-68. PubMed PMID: 23816179; PubMed Central PMCID: PMC3702406.

• Chiu YL, Shan L, Huang H, Haupt C, Bessell C, Canaday DH, Zhang H, Ho YC, Powell JD, Oelke M, Margolick JB, Blankson JN, Griffin DE, Schneck JP. Sprouty-2 regulates HIV-specific T cell polyfunctionality. J Clin Invest. 2013 Dec 2. pii: 70510. doi: 10.1172/JCI70510. [Epub ahead of print] PubMed PMID: 24292711; PubMed Central PMCID: PMC3871241.

• Durand C, Ambinder R, Blankson J, Forman S. HIV-1 and hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012 Jan;18(1 Suppl):S172-6. doi: 10.1016/j.bbmt.2011.10.027. Review. PubMed PMID: 22226103; PubMed Central PMCID: PMC3615639.

• Durand CM, Blankson JN, Siliciano RF. Developing strategies for HIV-1 eradication. Trends Immunol. 2012 Nov;33(11):554-62. doi:10.1016/j.it.2012.07.001. Epub 2012 Aug 3. Review. PubMed PMID: 22867874.

• Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell. 2013 Oct 24;155(3):540-51. doi: 10.1016/j.cell.2013.09.020. Epub 2013 Oct 24. PubMed PMID: 24243014; PubMed Central PMCID: PMC3896327.

• Laird GM, Eisele EE, Rabi SA, Lai J, Chioma S, Blankson JN, Siliciano JD, Siliciano RF. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay. PLoS Pathog. 2013;9(5):e1003398. doi: 10.1371/journal.ppat.1003398. Epub 2013 May 30. PubMed PMID: 23737751; PubMed Central PMCID: PMC3667757.

• O'Connell KA, Hegarty RW, Siliciano RF, Blankson JN. Viral suppression of multiple escape mutants by de novo CD8(+) T cell responses in a human immunodeficiency virus-1 infected elite suppressor. Retrovirology. 2011 Aug 3;8:63. doi: 10.1186/1742-4690-8-63. PubMed PMID: 21812985; PubMed Central PMCID: PMC3173334.

• O'Connell KA, Rabi SA, Siliciano RF, Blankson JN. CD4+ T cells from elite suppressors are more susceptible to HIV-1 but produce fewer virions than cells from chronic progressors. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):E689-98. doi: 10.1073/pnas.1108866108. Epub 2011 Aug 22. PubMed PMID: 21873218; PubMedCentral PMCID: PMC3174588.

• Pohlmeyer CW, Buckheit RW 3rd, Siliciano RF, Blankson JN. CD8+ T cells from HLA-B*57 elite suppressors effectively suppress replication of HIV-1 escape mutants. Retrovirology. 2013 Dec 12;10:152. doi: 10.1186/1742-4690-10-152. PubMed PMID: 24330837; PubMed Central PMCID: PMC3878989.

• Salgado M, Gandhi S, Buckheit RW, Berkenblit GV, Blankson JN. Evolution of an Attenuated HIV-1 Isolate in an Elite Suppressor. AIDS Res Hum Retroviruses. 2013 Nov 13. [Epub ahead of print] PubMed PMID: 24117037.

• Salgado M, Rabi SA, O'Connell KA, Buckheit RW 3rd, Bailey JR, Chaudhry AA, Breaud AR, Marzinke MA, Clarke W, Margolick JB, Siliciano RF, Blankson JN. Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy. Retrovirology. 2011 Dec 5;8:97. doi: 10.1186/1742-4690-8-97. PubMed PMID: 22141397; PubMed Central PMCID: PMC3293762.

• Salgado M, Swanson MD, Pohlmeyer CW, Buckheit RW 3rd, Wu J, Archin NM, Williams TM, Margolis DM, Siliciano RF, Garcia JV, Blankson JN. HLA-B*57 Elite Suppressor and Chronic Progressor HIV-1 Isolates Replicate Vigorously and Cause CD4+ T cell Depletion in Humanized BLT Mice. J Virol. 2014 Jan 3. [Epub ahead of print] PubMed PMID: 24390323.

• Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity. 2012 Mar 23;36(3):491-501. doi:10.1016/j.immuni.2012.01.014. Epub 2012 Mar 8. PubMed PMID: 22406268; PubMed Central PMCID: PMC3501645.

• Thayil SM, Ho YC, Bollinger RC, Blankson JN, Siliciano RF, Karakousis PC, Page KR. Mycobacterium tuberculosis complex enhances susceptibility of CD4 Tcells to HIV through a TLR2-mediated pathway. PLoS One. 2012;7(7):e41093. doi:10.1371/journal.pone.0041093. Epub 2012 Jul 23. PubMed PMID: 22844428; PubMed Central PMCID: PMC3402510.

• Wendel SK, Mullis CE, Eshleman SH, Blankson JN, Moore RD, Keruly JC, Brookmeyer R, Quinn TC, Laeyendecker O. Effect of natural and ARV-induced viral suppression and viral breakthrough on anti-HIV antibody proportion and avidity in patients with HIV-1 subtype B infection. PLoS One. 2013;8(2):e55525. doi:10.1371/journal.pone.0055525. Epub 2013 Feb 20. PubMed PMID: 23437058; PubMed Central PMCID: PMC3577851.

• Witwer KW, Watson AK, Blankson JN, Clements JE. Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients. Retrovirology. 2012 Jan 12;9:5. doi: 10.1186/1742-4690-9-5. PubMed PMID: 22240256; PubMed Central PMCID: PMC3292811.

Graduate Program Affiliations

• Immunology
• Cellular and Molecular Medicine