The focus of Mamuka Kvaratskhelia’s laboratory research is to understand HIV replication, cancer development and DNA repair processes at the molecular level. The knowledge obtained will be exploited to develop new, highly effective anti-viral and anti-cancer drugs. They primarily use mass spectrometry as both a proteomic and structural biology tool to elucidate the composition and architecture of key biological macromolecules. In particular, powerful mass spectrometric methodologies are being developed to obtain high-resolution structural information on protein-nucleic acid, protein-protein and drug-protein complexes. Proteomic applications in our laboratory include dissection of human proteins participating in HIV replication, revealing essential posttranslational modifications in proteins, discovery of biomarkers for the early detection of cancer and identification of factors responsible for anti-cancer drug resistance. They augment our structural and proteomic studies with traditional biochemical, molecular biology and biophysical analysis to obtain a comprehensive picture of these important biological events.
- Sharma, A; Larue, RC; Plumb, MR; Malani, N; Male, F; Slaughter, A; Kessl, JJ; Shkriabai, N; Coward, E; Aiyer, SS; Green, PL; Wu, L; Roth, MJ; Bushman, FD; Kvaratskhelia, M. BET proteins promote efficient murine leukemia virus integration at transcription start sites. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12036-41. doi: 10.1073/pnas.1307157110. Epub 2013 Jul 1.
- Engelman, A; Kessl, JJ; Kvaratskhelia, M. Allosteric inhibition of HIV-1 integrase activity. Curr Opin Chem Biol. 2013 Jun;17(3):339-45. doi: 10.1016/j.cbpa.2013.04.010. Epub 2013 May 3.
- Feng, L; Sharma, A; Slaughter, A; Jena, N; Koh, Y; Shkriabai, N; Larue, RC; Patel, PA; Mitsuya, H; Kessl, JJ; Engelman, A; Fuchs, JR; Kvaratskhelia, M. The A128T resistance mutation reveals aberrant protein multimerization as the primary mechanism of action of allosteric HIV-1 integrase inhibitors. J Biol Chem. 2013 May 31;288(22):15813-20. doi: 10.1074/jbc.M112.443390. Epub 2013 Apr 24.
- Jurado, KA; Wang, H; Slaughter, A; Feng, L; Kessl, JJ; Koh, Y; Wang, W; Ballandras-Colas, A; Patel, PA; Fuchs, JR; Kvaratskhelia, M; Engelman, A. Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8690-5. doi: 10.1073/pnas.1300703110. Epub 2013 Apr 22.
- Eidahl, JO; Crowe, BL; North, JA; McKee, CJ; Shkriabai, N; Feng, L; Plumb, M; Graham, RL; Gorelick, RJ; Hess, S; Poirier, MG; Foster, MP; Kvaratskhelia, M. Structural basis for high-affinity binding of LEDGF PWWP to mononucleosomes. Nucleic Acids Res. 2013 Apr 1;41(6):3924-36. doi: 10.1093/nar/gkt074. Epub 2013 Feb 8.
- Wang, H; Jurado, KA; Wu, X; Shun, MC; Li, X; Ferris, AL; Smith, SJ; Patel, PA; Fuchs, JR; Cherepanov, P; Kvaratskhelia, M; Hughes, SH; Engelman, A. HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor. Nucleic acids research. 2012 Oct 5;
- Doueiri, R; Anupam, R; Kvaratskhelia, M; Green, KB; Lairmore, MD; Green, PL. Comparative host protein interactions with HTLV-1 p30 and HTLV-2 p28: insights into difference in pathobiology of human retroviruses. Retrovirology. 2012 Aug 9;9:64
- Larue, R; Gupta, K; Wuensch, C; Shkriabai, N; Kessl, JJ; Danhart, E; Feng, L; Taltynov, O; Christ, F; Van, Duyne, GD; Debyser, Z; Foster, MP; Kvaratskhelia, M. Interaction of the HIV-1 intasome with Transportin 3 (TNPO3 or TRN-SR2). The Journal of biological chemistry. 2012 Aug 7;
- Kessl, JJ; Jena, N; Koh, Y; Taskent-Sezgin, H; Slaughter, A; Feng, L; de, Silva, S; Wu, L; Le, Grice, SF; Engelman, A; Fuchs, JR; Kvaratskhelia, M. Multimode, cooperative mechanism of action of allosteric HIV-1 integrase inhibitors. The Journal of biological chemistry. 2012 May 11;287(20):16801-11
- Kessl, JJ; Li, M; Ignatov, M; Shkriabai, N; Eidahl, JO; Feng, L; Musier-Forsyth, K; Craigie, R; Kvaratskhelia, M. FRET analysis reveals distinct conformations of IN tetramers in the presence of viral DNA or LEDGF/p75. Nucleic acids research. 2011 Nov 1;39(20):9009-22
- Postdoctoral Fellowships: Biological Chemistry Department of John Innes Center, England, UK; Biochemistry Department of the Dundee University, Scotland, UK and HIV Drug Resistance Program of the National Cancer Institute, MD, USA.
- Ph.D., 1990, The Georgian Institute and the Biotechnology Center of the Moscow State University, Biochemistry (Chemical Enzymology)