Melanie Ott, PhD
Senior Investigator, The Ott Lab, Gladstone Institute of Virology and Immunology
Professor, School of Medicine
Email: mott@gladstone.ucsf.edu
Biography
My laboratory is interested in the molecular mechanisms of viral pathogenesis. We focus on a variety of viruses including HIV-1, Hepatitis B and C Virus (HBV and HCV), Zika and SARS-CoV-2. We believe that identifying common host pathways involved in different viruses can lead to the discovery of panviral therapeutics. All are important public health problems and with HCV and HIV sharing common traits including high propensities to establish chronic infections and a lack of efficient vaccines, and Zika and SARS-CoV-2 causing global pandemics leading to death and disability. In recent years, we have established four main technologies to study these viruses—rapid quantitative tests, human organoids, a viral protein library and transcriptomics and chromatin biology. We recently applied these technologies to the studies of SARS-CoV-2, leading to the development of a new direct detection CRISPR diagnostic and the identification of shared host factors necessary for the replication of SARS-CoV-2 and common cold coronaviruses. SARS-CoV-2, 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:
• characterizing influenza B infection in human airway organoids
• developing a new hepatitis B clone to screen for host factors regulating cccDNA formation
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- Cho S, Schroeder S, Ott M. CYCLINg through transcription: posttranslational modifications of P-TEFb regulate transcription elongation. . 2010 May; 9(9):1697-705.
- Ott M, Verdin E. HAT trick: p300, small molecule, inhibitor. Chem Biol. 2010 May 28; 17(5):417-8.
- 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. . 2010 Mar 18; 7(3):234-44.
- 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.
- Ott M, Fricker G, Bauer B. Pregnane X receptor (PXR) regulates P-glycoprotein at the blood-brain barrier: functional similarities between pig and human PXR. J Pharmacol Exp Ther. 2009 Apr; 329(1):141-9.
- Nakamura K, Nemani VM, Wallender EK, Kaehlcke K, Ott M, Edwards RH. Optical reporters for the conformation of alpha-synuclein reveal a specific interaction with mitochondria. J Neurosci. 2008 Nov 19; 28(47):12305-17.
- Kwon HS, Ott M. The ups and downs of SIRT1. Trends Biochem Sci. 2008 Nov; 33(11):517-25.
- 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. . 2008 Mar 13; 3(3):158-67.
- Hetzer C, Bisgrove D, Cohen MS, Pedal A, Kaehlcke K, Speyerer A, Bartscherer K, Taunton J, Ott M. Recruitment and activation of RSK2 by HIV-1 Tat. PLoS One. 2007 Jan 17; 2(1):e151.
- Nieters A, Kallinowski B, Brennan P, Ott M, Maynadié M, Benavente Y, Foretova L, Cocco PL, Staines A, Vornanen M, Whitby D, Boffetta P, Becker N, De Sanjosé S. Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH. Gastroenterology. 2006 Dec; 131(6):1879-86.
- 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.
- Dormeyer W, Ott M, Schnölzer M. Analysis of p300 acetyltransferase substrate specificity by MALDI TOF mass spectrometry. Methods. 2005 Aug; 36(4):376-82.
- Hetzer C, Dormeyer W, Schnölzer M, Ott M. Decoding Tat: the biology of HIV Tat posttranslational modifications. Microbes Infect. 2005 Oct; 7(13):1364-9.
- Dormeyer W, Ott M, Schnölzer M. Probing lysine acetylation in proteins: strategies, limitations, and pitfalls of in vitro acetyltransferase assays. Mol Cell Proteomics. 2005 Sep; 4(9):1226-39.
- 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.
- Schwer B, Ren S, Pietschmann T, Kartenbeck J, Kaehlcke K, Bartenschlager R, Yen TS, Ott M. Targeting of hepatitis C virus core protein to mitochondria through a novel C-terminal localization motif. J Virol. 2004 Aug; 78(15):7958-68.
- Witte V, Laffert B, Rosorius O, Lischka P, Blume K, Galler G, Stilper A, Willbold D, D'Aloja P, Sixt M, Kolanus J, Ott M, Kolanus W, Schuler G, Baur AS. HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane. Mol Cell. 2004 Jan 30; 13(2):179-90.
- 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.
- Dormeyer W, Dorr A, Ott M, Schnölzer M. Acetylation of the HIV-1 Tat protein: an in vitro study. Anal Bioanal Chem. 2003 Aug; 376(7):994-1005.
- 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.
- Fritzsching B, Schwer B, Kartenbeck J, Pedal A, Horejsi V, Ott M. Release and intercellular transfer of cell surface CD81 via microparticles. J Immunol. 2002 Nov 15; 169(10):5531-7.
- 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.
- 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 03; 21(11):2715-23.
- 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.