Larisa Poluektova, MD, Ph.D.
Ongoing Projects: In 2000 I made a unique observation that human lymphocytes transplanted intraperitoneally in SCID mice migrated in the murine brain, if HIV-1-infected autologous macrophages were present there. The interaction between human lymphocytes and HIV-1-infected autologous human macrophages in brain environment leads to the development of HIV-1-specific cellular immune responses. This observation prompted us to adapt this murine model to investigate: 1) earlier consequences of HIV-1 associated CNS disease; 2) mechanisms of local brain damage and repair; 3) utilize humanized SCID mice as a test system for HIV-1 vaccine evaluation and 4) screen potential vaccine candidates. Analyzing brain pathology in HIV-1 encephalitic mice, we found dividing cells in specific regions of ongoing neurogenesis. This observation stimulated our interest to study the ability of chronically inflamed and intoxicated HIV-1 brain tissue to self-repair by possible replacement of neuronal loss. Selected Recent Publications: 1. Gorantla S, Sneller H, Gebhardt C, Persinger A, Ikezu T, Duke C, Bowers W, Wood C, Gendelman HE, Dewhurstand Poluektova L. Immunization of humanized mice with adenoviral vector encoding HIV-1 proteins accelerates immunodeficiency following viral challenge. J Virol. (submitted October, 2007 Manuscript JVI02208-07). 2. Gorantla S, Liu J, Wang T, Holguin A, Sneller H, Dou H, Kipnis J, Poluektova L, and Gendelman HE. Modulation of Innate Immunity by Copolymer-1 Leads to Neuroprotection in Murine HIV-1 Encephalitis. Glia In Press, 2007. 3. Gorantla S, Liu J, Sneller H, Dou H, Holguin A, Smith L, Ikezu T, Volsky DJ, Poluektova L, Gendelman HE. Copolymer-1 induces adaptive immune anti-inflammatory glial and neuroprotective responses in a murine model of HIV-1 encephalitis. J Immunol. Oct 1;179(7):4345-56, 2007. 4. Gorantla S, Sneller H, Walters L, Sharp JG, Pirruccello SJ, West JT, Wood C, Dewhurst S, Gendelman HE, Poluektova L. Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2-/-{gamma}c-/- Mice. J Virol. Mar;81(6):2700-12, 2007. 5. Dou H, Destache CJ, Morehead JR, Mosley RL, Boska MD, Kingsley J, Gorantla S, Poluektova L, Nelson JA, Chaubal M, Werling J, Kipp J, Rabinow B, Gendelman HE. Development of a macrophage-based nanoparticle system for anti-retroviral drug delivery. Blood. Oct 15;108(8):2827-35, 2006. 6. Gorantla S, Dou H, Boska M, Destache CJ, Nelson J, Poluektova L, Rabinow BE, Gendelman HE, Mosley RL. Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery. J Leukoc Biol. Nov;80(5):1165-74, 2006. 7. Persidsky Y, Poluektova L. Immune privilege and HIV-1 persistence in the CNS. Immunol Rev. Oct;213:180-94, 2006. 8. Li B, Duysen EG, Poluektova LY, Murrin LC, Lockridge O. Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase. Toxicol Appl Pharmacol. Jul 15;214(2):152-65, 2006. 9. Poluektova L, Meyer V, Walters L, Paez X, Gendelman HE. Macrophage-induced inflammation affects hippocampal plasticity and neuronal development in a murine model of HIV-1 encephalitis. Glia. Dec;52(4):344-53, 2005. 10. Potula R, Poluektova L, Knipe B, Chrastil J, Heilman D, Dou H, Takikawa O, Munn DH, Gendelman HE, Persidsky Y. Inhibition of indoleamine 2,3-dioxygenase (IDO) enhances elimination of virus-infected macrophages in an animal model of HIV-1 encephalitis. Blood. Oct 1;106(7):2382-90, 2005. 11. Gorantla S, Santos K, Meyer V, Dewhurst S, Bowers WJ, Federoff HJ, Gendelman HE, Poluektova L. Human Dendritic Cells Transduced with Herpes Simplex Virus Amplicons Encoding Human Immunodeficiency Virus Type 1 (HIV-1) gp120 Elicit Adaptive Immune Responses from Human Cells Engrafted into NOD/SCID Mice and Confer Partial Protection against HIV-1 Challenge. J Virol. Feb;79(4):2124-32, 2005. 12.Poluektova, L., Gorantla, S., Faraci, J., Birusingh, K., Dou, H., and Howard E. Gendelman. Neuroregulatory events follow adaptive immune-mediated elimination of HIV-1-infected macrophages: Studies in a murine model of viral encephalitis. J.Immunol., Jun 15;172(12):7610-7, 2004. |
|
