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    Melanie Ott, MD, PhD

    TitleProfessor
    SchoolUCSF School of Medicine
    DepartmentMedicine
    Address1650 Owens St
    San Francisco CA 94107
    Phone415-734-4807
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      Collapse Biography 
      Collapse Education and Training
      University of Frankfurt/MainM.D1991
      Picower Graduate SchoolPh.D1997

      Collapse Overview 
      Collapse Interests
      My laboratory is interested in the molecular mechanisms of viral pathogenesis. We focus on two viruses: HIV-1 and Hepatitis C Virus (HCV). Both are important public health problems and share common traits including high propensities to establish chronic infections and a lack of efficient vaccines., Our HIV efforts focus on viral transcription and latency as remaining barriers to viral eradication. We focus specifically on posttranslational modifications of the HIV transactivator Tat as potential targets to manipulate viral transcription therapeutically. In the past, we defined Tat acetylation and deacetylation as important steps in the Tat transactivation cycle and recently identified acetylation of the RNA polymerase II as an important regulatory step in transcription elongation. We are also interested in Tat-host cell interactions, specifically how Tat expression in infected T cells dysregulates immune functions and supports a premature aging syndrome observed in HIV+ individuals., Our HCV research focuses on the interaction of viral proteins with intracellular lipid droplets. These organelles play a critical role in the assembly of HCV progeny virions and are occupied in infected cells by the HCV nucleocapsid core. We recently showed that core interacts with the triglyceride-synthesizing enzyme DGAT1, and that this interaction plays a central role in the recruitment of core to lipid droplets. We are currently defining the role of lipid droplets in related viruses such as Dengue and Zika Virus and performed a comprehensive protein:protein interaction analysis of HCV proteins and hepatoma cells, which identified many novel factors involved in the infection. Both, HCV and HIV research in my laboratory includes replication studies with infectious viral clones, which are performed in the BSL3 laboratory., Recent rotation projects in the lab:, - defining the interaction of Dengue virus with lipid droplets;, - characterizing a new posttranslational modification of Tat at lysine 71;, - validating interaction partners of SIRT1 in T cells.

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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Khan S, Woodruff EM, Trapecar M, Fontaine KA, Ezaki A, Borbet TC, Ott M, Sanjabi S. Dampened antiviral immunity to intravaginal exposure to RNA viral pathogens allows enhanced viral replication. J Exp Med. 2016 Nov 16. PMID: 27852793.
        View in: PubMed
      2. Shirakawa K, Wang L, Man N, Maksimoska J, Sorum AW, Lim HW, Lee IS, Shimazu T, Newman JC, Schröder S, Ott M, Marmorstein R, Meier J, Nimer S, Verdin E. Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity. Elife. 2016; 5. PMID: 27244239.
        View in: PubMed
      3. Ali I, Ramage H, Boehm D, Dirk LM, Sakane N, Hanada K, Pagans S, Kaehlcke K, Aull K, Weinberger L, Trievel R, Schnoelzer M, Kamada M, Houtz R, Ott M. The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7. J Biol Chem. 2016 Jul 29; 291(31):16240-8. PMID: 27235396.
        View in: PubMed
      4. Meyers NL, Fontaine KA, Kumar GR, Ott M. Entangled in a membranous web: ER and lipid droplet reorganization during hepatitis C virus infection. Curr Opin Cell Biol. 2016 Aug; 41:117-24. PMID: 27240021.
        View in: PubMed
      5. Conrad RJ, Ott M. Therapeutics Targeting Protein Acetylation Perturb Latency of Human Viruses. ACS Chem Biol. 2016 Mar 18; 11(3):669-80. PMID: 26845514.
        View in: PubMed
      6. Jeng MY, Ali I, Ott M. Manipulation of the host protein acetylation network by human immunodeficiency virus type 1. Crit Rev Biochem Mol Biol. 2015; 50(4):314-25. PMID: 26329395.
        View in: PubMed
      7. Lim HW, Kang SG, Ryu JK, Schilling B, Fei M, Lee IS, Kehasse A, Shirakawa K, Yokoyama M, Schnölzer M, Kasler HG, Kwon HS, Gibson BW, Sato H, Akassoglou K, Xiao C, Littman DR, Ott M, Verdin E. SIRT1 deacetylates ROR?t and enhances Th17 cell generation. J Exp Med. 2015 May 4; 212(5):607-17. PMID: 25918343; PMCID: PMC4419343.
      8. Vogt DA, Ott M. Membrane Flotation Assay. Bio Protoc. 2015 Apr 5; 5(7). PMID: 27540564.
        View in: PubMed
      9. Ramage HR, Kumar GR, Verschueren E, Johnson JR, Von Dollen J, Johnson T, Newton B, Shah P, Horner J, Krogan NJ, Ott M. A combined proteomics/genomics approach links hepatitis C virus infection with nonsense-mediated mRNA decay. Mol Cell. 2015 Jan 22; 57(2):329-40. PMID: 25616068; PMCID: PMC4305532 [Available on 01/22/16].
      10. Verdin E, Ott M. 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nat Rev Mol Cell Biol. 2015 Apr; 16(4):258-64. PMID: 25549891.
        View in: PubMed
      11. Camus G, Schweiger M, Herker E, Harris C, Kondratowicz AS, Tsou CL, Farese RV, Herath K, Previs SF, Roddy TP, Pinto S, Zechner R, Ott M. The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)-mediated lipid mobilization and enhances the ATGL interaction with comparative gene identification 58 (CGI-58) and lipid droplets. J Biol Chem. 2014 Dec 26; 289(52):35770-80. PMID: 25381252; PMCID: PMC4276846 [Available on 12/26/15].
      12. Schröder S, Herker E, Itzen F, He D, Thomas S, Gilchrist DA, Kaehlcke K, Cho S, Pollard KS, Capra JA, Schnölzer M, Cole PA, Geyer M, Bruneau BG, Adelman K, Ott M. Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells. Mol Cell. 2013 Nov 7; 52(3):314-24. PMID: 24207025; PMCID: PMC3936344.
      13. Webster B, Ott M, Greene WC. Evasion of superinfection exclusion and elimination of primary viral RNA by an adapted strain of hepatitis C virus. J Virol. 2013 Dec; 87(24):13354-69. PMID: 24089557; PMCID: PMC3838274.
      14. Verdin E, Ott M. Acetylphosphate: a novel link between lysine acetylation and intermediary metabolism in bacteria. Mol Cell. 2013 Jul 25; 51(2):132-4. PMID: 23870140.
        View in: PubMed
      15. Boehm D, Conrad RJ, Ott M. Bromodomain proteins in HIV infection. Viruses. 2013 Jun; 5(6):1571-86. PMID: 23793227; PMCID: PMC3717722.
      16. Ott M, Verdin E. Three rules for HIV latency: location, location, and location. Cell Host Microbe. 2013 Jun 12; 13(6):625-6. PMID: 23768485; PMCID: PMC3998752.
      17. Camus G, Ott M. How the antiviral immune response boosts liver fat. Nat Med. 2013 Jun; 19(6):671-2. PMID: 23744144.
        View in: PubMed
      18. Vogt DA, Camus G, Herker E, Webster BR, Tsou CL, Greene WC, Yen TS, Ott M. Lipid droplet-binding protein TIP47 regulates hepatitis C Virus RNA replication through interaction with the viral NS5A protein. PLoS Pathog. 2013; 9(4):e1003302. PMID: 23593007; PMCID: PMC3623766.
      19. Camus G, Herker E, Modi AA, Haas JT, Ramage HR, Farese RV, Ott M. Diacylglycerol acyltransferase-1 localizes hepatitis C virus NS5A protein to lipid droplets and enhances NS5A interaction with the viral capsid core. J Biol Chem. 2013 Apr 5; 288(14):9915-23. PMID: 23420847; PMCID: PMC3617291.
      20. Camus G, Vogt DA, Kondratowicz AS, Ott M. Lipid droplets and viral infections. Methods Cell Biol. 2013; 116:167-90. PMID: 24099293.
        View in: PubMed
      21. Webster B, Wissing S, Herker E, Ott M, Greene WC. Rapid intracellular competition between hepatitis C viral genomes as a result of mitosis. J Virol. 2013 Jan; 87(1):581-96. PMID: 23097449; PMCID: PMC3536371.
      22. Kwon HS, Lim HW, Wu J, Schnölzer M, Verdin E, Ott M. Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells. J Immunol. 2012 Mar 15; 188(6):2712-21. PMID: 22312127; PMCID: PMC3478122.
      23. Boehm D, Calvanese V, Dar RD, Xing S, Schroeder S, Martins L, Aull K, Li PC, Planelles V, Bradner JE, Zhou MM, Siliciano RF, Weinberger L, Verdin E, Ott M. BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism. Cell Cycle. 2013 Feb 1; 12(3):452-62. PMID: 23255218; PMCID: PMC3587446.
      24. Ott M, Geyer M, Zhou Q. The control of HIV transcription: keeping RNA polymerase II on track. Cell Host Microbe. 2011 Nov 17; 10(5):426-35. PMID: 22100159; PMCID: PMC3478145.
      25. Herker E, Ott M. Emerging role of lipid droplets in host/pathogen interactions. J Biol Chem. 2012 Jan 20; 287(4):2280-7. PMID: 22090026; PMCID: PMC3268388.
      26. Schröder S, Cho S, Zeng L, Zhang Q, Kaehlcke K, Mak L, Lau J, Bisgrove D, Schnölzer M, Verdin E, Zhou MM, Ott M. Two-pronged binding with bromodomain-containing protein 4 liberates positive transcription elongation factor b from inactive ribonucleoprotein complexes. J Biol Chem. 2012 Jan 6; 287(2):1090-9. PMID: 22084242; PMCID: PMC3256921.
      27. Harris C, Herker E, Farese RV, Ott M. Hepatitis C virus core protein decreases lipid droplet turnover: a mechanism for core-induced steatosis. J Biol Chem. 2011 Dec 9; 286(49):42615-25. PMID: 21984835; PMCID: PMC3234948.
      28. Sakane N, Kwon HS, Pagans S, Kaehlcke K, Mizusawa Y, Kamada M, Lassen KG, Chan J, Greene WC, Schnoelzer M, Ott M. Activation of HIV transcription by the viral Tat protein requires a demethylation step mediated by lysine-specific demethylase 1 (LSD1/KDM1). PLoS Pathog. 2011 Aug; 7(8):e1002184. PMID: 21876670; PMCID: PMC3158049.
      29. Herker E, Ott M. Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol Metab. 2011 Jun; 22(6):241-8. PMID: 21497514; PMCID: PMC3118981.
      30. Herker E, Harris C, Hernandez C, Carpentier A, Kaehlcke K, Rosenberg AR, Farese RV, Ott M. Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1. Nat Med. 2010 Nov; 16(11):1295-8. PMID: 20935628; PMCID: PMC3431199.
      31. Min SW, Cho SH, Zhou Y, Schroeder S, Haroutunian V, Seeley WW, Huang EJ, Shen Y, Masliah E, Mukherjee C, Meyers D, Cole PA, Ott M, Gan L. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron. 2010 Sep 23; 67(6):953-66. PMID: 20869593; PMCID: PMC3035103.
      32. Pagans S, Sakane N, Schnölzer M, Ott M. Characterization of HIV Tat modifications using novel methyl-lysine-specific antibodies. Methods. 2011 Jan; 53(1):91-6. PMID: 20615470; PMCID: PMC3478124.
      33. Cho S, Schroeder S, Ott M. CYCLINg through transcription: posttranslational modifications of P-TEFb regulate transcription elongation. Cell Cycle. 2010 May; 9(9):1697-705. PMID: 20436276; PMCID: PMC2956491.
      34. Ott M, Verdin E. HAT trick: p300, small molecule, inhibitor. Chem Biol. 2010 May 28; 17(5):417-8. PMID: 20534339.
        View in: PubMed
      35. Pagans S, Kauder SE, Kaehlcke K, Sakane N, Schroeder S, Dormeyer W, Trievel RC, Verdin E, Schnolzer M, Ott M. The Cellular lysine methyltransferase Set7/9-KMT7 binds HIV-1 TAR RNA, monomethylates the viral transactivator Tat, and enhances HIV transcription. Cell Host Microbe. 2010 Mar 18; 7(3):234-44. PMID: 20227666; PMCID: PMC2844784.
      36. Cho S, Schroeder S, Kaehlcke K, Kwon HS, Pedal A, Herker E, Schnoelzer M, Ott M. Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells. EMBO J. 2009 May 20; 28(10):1407-17. PMID: 19387490; PMCID: PMC2688543.
      37. Kwon HS, Ott M. The ups and downs of SIRT1. Trends Biochem Sci. 2008 Nov; 33(11):517-25. PMID: 18805010.
        View in: PubMed
      38. Kwon HS, Brent MM, Getachew R, Jayakumar P, Chen LF, Schnolzer M, McBurney MW, Marmorstein R, Greene WC, Ott M. Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation. Cell Host Microbe. 2008 Mar 13; 3(3):158-67. PMID: 18329615; PMCID: PMC2680745.
      39. Mahmoudi T, Parra M, Vries RG, Kauder SE, Verrijzer CP, Ott M, Verdin E. The SWI/SNF chromatin-remodeling complex is a cofactor for Tat transactivation of the HIV promoter. J Biol Chem. 2006 Jul 21; 281(29):19960-8. PMID: 16687403.
        View in: PubMed
      40. Pagans S, Pedal A, North BJ, Kaehlcke K, Marshall BL, Dorr A, Hetzer-Egger C, Henklein P, Frye R, McBurney MW, Hruby H, Jung M, Verdin E, Ott M. SIRT1 regulates HIV transcription via Tat deacetylation. PLoS Biol. 2005 Feb; 3(2):e41. PMID: 15719057; PMCID: PMC546329.
      41. Ott M, Dorr A, Hetzer-Egger C, Kaehlcke K, Schnolzer M, Henklein P, Cole P, Zhou MM, Verdin E. Tat acetylation: a regulatory switch between early and late phases in HIV transcription elongation. Novartis Found Symp. 2004; 259:182-93; discussion 193-6, 223-5. PMID: 15171254.
        View in: PubMed
      42. Kaehlcke K, Dorr A, Hetzer-Egger C, Kiermer V, Henklein P, Schnoelzer M, Loret E, Cole PA, Verdin E, Ott M. Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation. Mol Cell. 2003 Jul; 12(1):167-76. PMID: 12887902.
        View in: PubMed
      43. Schwer B, North BJ, Frye RA, Ott M, Verdin E. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol. 2002 Aug 19; 158(4):647-57. PMID: 12186850; PMCID: PMC2174009.
      44. Dorr A, Kiermer V, Pedal A, Rackwitz HR, Henklein P, Schubert U, Zhou MM, Verdin E, Ott M. Transcriptional synergy between Tat and PCAF is dependent on the binding of acetylated Tat to the PCAF bromodomain. EMBO J. 2002 Jun 3; 21(11):2715-23. PMID: 12032084; PMCID: PMC125383.
      45. Mujtaba S, He Y, Zeng L, Farooq A, Carlson JE, Ott M, Verdin E, Zhou MM. Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. Mol Cell. 2002 Mar; 9(3):575-86. PMID: 11931765.
        View in: PubMed
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