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Contact Us
The George Washington
Department of Microbiology, Immunology, and Tropical Medicine
2300 Eye Street NW,
Ross Hall 736
Washington, DC 20037
Phone: (202) 994-3532
email: mitm@gwu.edu
Burkinsky Lab
Michael Burkinsky, M.D, Ph.D.
Professor and Interim-Chair of Microbiology, Immunology, and Tropical Medicine
Contact Information:
Department of Microbiology,
Immunology and Tropical Medicine
The George Washington University
Medical Center
Ross Hall, Room 736
2300 Eye Street, NW
Washington, DC 20037 USA
Phone: +1 202 994 2036
Fax: +1 202 994 2913
E-mail: mbukrins@gwu.edu
Research Summary
Dr. Bukrinsky's research focus is on HIV biology and inflammatory diseases. The following projects are pursued: i) analysis of cholesterol metabolism in HIV-infected cells; ii) design and analysis of anti-HIV compounds; iii) analysis of molecular mechanisms of HIV-1 translocation from the cytoplasm into the nucleus of infected cells; iv) studies on the role of a new pro-inflammatory factor discovered by Dr. Bukrinsky - extracellular cyclophilin - in inflammatory disease pathogenesis; v) studies of HIV infection of macrophages. Dr. Bukrinsky is also actively involved in education activities, including international programs with Russia and Australia.
Along these lines, they have made the following major discoveries:
- The laboratory has demonstrated the role of extracellular cyclophilin as a pathogenic factor in asthma and rheumatoid arthritis and identified CD147 as a signaling receptor for extracellular cyclophilins A and B. Their current work is aimed at the molecular mechanisms of cyclophilin-CD147 interaction and the involvement of this interaction in regulation of immune responses and in the pathogenesis of other inflammatory diseases, such as atherosclerosis. These studies are expected to suggest novel therapeutic approaches for treating these diseases.
- Their laboratory pioneered studies of HIV-1 nuclear transport mechanisms and was the first to describe the role of matrix protein (MA) and Vpr in this process. They continue these studies focusing on interactions between the viral pre-integration complex and cellular proteins. In addition to contributing to the general understanding of HIV-1 biology, results of these studies are expected to provide a basis for design of anti-HIV compounds.
- The laboratory has designed a series of compounds that target HIV-1 nuclear import. They also demonstrated potent anti-HIV activity of compounds stimulating cholesterol efflux from cells, such as agonists of the nuclear receptor LXR.
- Through their research, Dr. Bukrinsky's laboratory has found that HIV-1 infection of macrophages induces secretion of beta-chemokines and have analyzed the molecular mechanisms involved in beta-chemokine production. Their group published a seminal paper in Nature demonstrating that beta-chemokines do not inhibit HIV-1 infection of these cells. A series of reports from Dr. Bukrinsky's laboratory has demonstrated the production of nitric oxide by HIV-infected macrophages and the role of this mechanism in neuropathology of HIV infection. They also analyzed the effect of activation on HIV infection of macrophage and T cells and demonstrated that activating stimuli, such as LPS, protect macrophages from infection.
Selected Publications
Bukrinsky M.I., Nottet H.S.L.M., Schmidtmayerova H., Dubrovsky L., Flanagan C.R., Mullins M.E., Lipton S.A., and Gendelman H.E. (1995). Regulation of nitric oxide synthase activity in HIV-1 monocytes: Implications for HlV-associated neurological diseases. J. Exp. Med. 181:735-745.
Schmidtmayerova H., Sherry B., and Bukrinsky M. (1996). Differential effect of bï€ chemokines on HIV-1 replication in T lymphocytes and macrophages. Nature 382:767.
Popov S., Rexach M., Zybarth G., Reiling N., Lee M.-A., Ratner L., Lane C.M., Moore M.S., Blobel G., and Bukrinsky M.I. (1998). Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J. 17:909-917.
Yurchenko V., Zybarth G., O'Connor M., Dai W.W., Franchin G., Hao T., Guo H, Hung H.-C., Toole B., Gallay P., Sherry B., and Bukrinsky M. (2002). Active-site residues of cyclophilin A are crucial for its signaling activity via CD147. J. Biol. Chem. 277:22959-22965.
Haffar O, Dubrovsky L, Lowe R, Berro R, Kashanchi F, Godden J, Vanpouille C, Bajorath J, and Bukrinsky M (2005). Oxadiazols: a new class of rationally designed anti-HIV compounds targeting nuclear localization signal of the viral matrix protein. J. Virol. 79:13028-13036.
Iordanskiy S, Berro R, Altieri M, Kashanchi F, and Bukrinsky M. (2006). Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse transcription complexes determines their capacity to integrate into chromatin. Retrovirology 3:4.
Mujawar Z, Rose H, Morrow MP, Pushkarsky T, Dubrovsky L, Mukhamedova N, Fu Y, Dart A, Orenstein JM, Bobryshev YV, Bukrinsky M*, and Sviridov D (2006). Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol. 4:e365.
Crowe SM, Westhorpe CL, Mukhamedova N, Jaworowski A, Sviridov D, Bukrinsky M. (2009). The macrophage: the intersection between HIV infection and atherosclerosis. J Leukoc Biol. 87:589-598.
Morrow MP, Grant A, Mujawar Z, Dubrovsky L, Pushkarsky T, Kiselyeva Y, Jennelle L, Mukhamedova N, Remaley AT, Kashanchi F, Sviridov D, Bukrinsky M. (2010). Stimulation of the liver X receptor pathway inhibits HIV-1 replication via induction of ATP-binding cassette transporter A1. Mol Pharmacol. 78:215-225.
Levin A, Loyter A, Bukrinsky M. (2010). Strategies to inhibit viral protein nuclear import: HIV-1 as a target. Biochim Biophys Acta In press.
Faculty Members
Sergey Iordanskiy
Assistant Professor
e-mail: siord@gwu.edu
Lab Members
Larisa Dubrovsky
Research Associate
e-mail: ld405@gwu.edu
Tatiana Pushkarsky
Research Scientist
e-mail: tpushk@gwu.edu
Lucas Jennelle
Research Assistant - PhD Student
e-mail: ljennell@gwu.edu
Steven Santos
PhD Student
e-mail: ssantos@gwu.edu