David Arnott

Senior Scientist, Protein Chemistry

POSTDOC MENTOR

"A roadmap for postdoctoral projects is to select an area of technology for development, and apply the new methods to a biological problem in collaboration with other scientists in Genentech Research."

• 15
  years at Genentech
• 21
  publications (2010-12)

The Microchemistry and Proteomics laboratory is part of the Protein Chemistry department, and develops and applies proteomic technology to basic research and drug discovery at Genentech. Key technologies include mass spectrometry, protein sequencing, protein and peptide separations, and chemical and enzymatic protein manipulation.

We are well equipped with mass spectrometers (LTQ-FT, LTQ-orbitrap, QSTAR-XL, QTRAP-4000, Voyager DE-STR et al.) HPLCs, electrophoresis equipment, and related gadgetry.

Methods and technology development are important aspects of our efforts, and active work is being done in the areas of targeted proteomics, quantitation, and various PTM detection and enrichment schemes. We are also interested in the relatively new field of ""top-down"" proteomics, and plan to upgrade or LTQ mass spectrometer to enable electron-transfer dissociation in the near future. A roadmap for postdoctoral projects is to select an area of technology for development, and apply the new methods to a biological problem in collaboration with other scientists in Genentech Research.

• My Focus

  Research projects include both unbiased proteomic analyses and targeted detection and quantification of selected proteins in complex biological samples. A common type of project is the mapping of protein-protein interactions to better understand the mechanisms and regulation of signal transduction pathways.

  Posttranslational modification analysis is another common project; most often phosphorylation, but also ubiquitination, glycosylation, disulfides, etc. Quantitative and dynamic protein and PTM measurements are becoming increasingly important aspects of such projects. De novo sequencing is a less common but nevertheless important type of project; on several occasions we have sequenced entire monoclonal antibodies to enable cloning where no cell line or DNA sequence was available.

• Publications

  • Glycan shifting on hepatitis C virus (HCV) e2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies

    Journal of Molecular Biology, 2013, ISSN: 1089-8638

    Pantua, Homer; Diao, Jingyu; Ultsch, Mark; Hazen, Meredith; Mathieu, Mary; McCutcheon, Krista; Takeda, Kentaro; Date, Shailesh; Cheung, Tommy K; Phung, Qui; Hass, Phil; Arnott, David; Hongo, Jo-Anne; Matthews, David J; Brown, Alex; Patel, Arvind H; Kelley, Robert F; Eigenbrot, Charles; Kapadia, Sharookh B

     View on PubMed

  • OTUB1 modulates c-IAP1 stability to regulate signalling pathways

    EMBO Journal, 2013, ISSN: 0261-4189

    Goncharov, Tatiana; Niessen, Kyle; de Almagro, Maria Cristina; Izrael-Tomasevic, Anita; Fedorova, Anna V; Varfolomeev, Eugene; Arnott, David; Deshayes, Kurt; Kirkpatrick, Donald S; Vucic, Domagoj

     View on PubMed

  • Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to the autophagy machinery

    EMBO Reports, 2013, ISSN: 1469-221X

    Lee, Dong Yun; Arnott, David; Brown, Eric J.

     View on PubMed

  • Furin-cleaved PCSK9 is active and modulates LDL receptor and serum cholesterol levels

    Journal of Biological Chemistry, 2012, ISSN: 0021-9258

    Lipari, Michael T; Li, Wei; Moran, Paul; Kong-Beltran, Monica; Sai, Tao; Lai, Joyce; Lin, S Jack; Kolumam, Ganesh; Zavala-Solorio, Jose; Izrael-Tomasevic, Anita; Arnott, David; Wang, Jianyong; Peterson, Andrew S; Kirchhofer, Daniel

     View on PubMed

  • Phosphorylation of NLRC4 is critical for inflammasome activation

    Nature, 2012, ISSN: 0028-0836

    Qu, Yan; Misaghi, Shahram; Izrael-Tomasevic, Anita; Newton, Kim; Gilmour, Laurie L; Lamkanfi, Mohamed; Louie, Salina; Kayagaki, Nobuhiko; Liu, Jinfeng; Kömüves, László; Cupp, James E; Arnott, David; Monack, Denise; Dixit, Vishva M

     View on PubMed

  • Phosphorylation-dependent activity of the deubiquitinase DUBA

    Nature Structural & Molecular Biology, 2012, ISSN: 1545-9985

    Huang, Oscar W; Ma, Xiaolei; Yin, Jianping; Flinders, Jeremy; Maurer, Till; Kayagaki, Nobuhiko; Phung, Qui; Bosanac, Ivan; Arnott, David; Dixit, Vishva M; Hymowitz, Sarah G; Starovasnik, Melissa A; Cochran, Andrea G

     View on PubMed

  • Manipulating the Mass Spectrometric Properties of Peptides through Selective Chemical Modification.

    Sample Preparation in Biological Mass Spectrometry, 2011, p. 19-40, Editors: Alexander R. Ivanov and Alexander V. Lazarev, Publisher: Spinger, DOI: 10.1007/978-94-007-0828-0_2, ISBN: 978-94-007-0758-0(H).

    David Arnott; Peter S. Liu; Patricia Molina; Lilian Phu; Wendy N. Sandoval

     View on PubMed

  • Preparation of Distinct Ubiquitin Chain Reagents of High Purity and Yield

    Structure, 10 Aug 2011, vol. 19, no. 8, p. 1053-63, ISSN: 1878-4186.

    Dong, Ken C; Helgason, Elizabeth; Yu, Christine; Phu, Lilian; Arnott, David P; Bosanac, Ivan; Compaan, Deanne M; Huang, Oscar W; Fedorova, Anna V; Kirkpatrick, Donald S; Hymowitz, Sarah G; Dueber, Erin C

     View on PubMed

  • Improved quantitative mass spectrometry methods for characterizing complex ubiquitin signals

    Molecular & Cellular Proteomics, 2011, ISSN: 1535-9476

    Phu, L.; Izrael-Tomasevic, A.; Matsumoto, M.L.; Bustos, D.; Dynek, J.N.; Fedorova, A.V.; Bakalarski, C.E.; Arnott, D.; Deshayes, K.; Dixit, V.M.; Kelley, R.F.; Vucic, D.; Kirkpatrick, D.S.

  • COP1 is a tumour suppressor that causes degradation of ETS transcription factors.

    Nature, 2011, ISSN: 0028-0836

    Vitari, A.C.; Leong, K.G.; Newton, K.; Yee, C.; O'Rourke, K.; Liu, J.; Phu, L.; Vij, R.; Ferrando, R.; Couto, S.S.; Mohan, S.; Pandita, A.; Hongo, J.A.; Arnott, D.; Wertz, I.E.; Gao, W.Q.; French, D.M.; Dixit, V.M.

     View on PubMed

  • Resurrection of a clinical antibody: Template proteogenomic de novo proteomic sequencing and reverse engineering of an anti-lymphotoxin-α antibody.

    Proteomics, 2011, ISSN: 1615-9853

    Castellana, N.; McCutcheon, K.; Pham, V.; Harden, K.; Nguyen, A.; Young, J.; Adams, C.; Schroeder, K.; Arnott, D.; Bafna, V.; Grogan, J.; Lill, J.

  • Ubiquitin Binding to A20 ZnF4 Is Required for Modulation of NF-κB Signaling.

    Molecular Cell, 2010, ISSN: 1097-2765

    Bosanac, I.; Wertz, I.E.; Pan, B.; Yu, C.; Kusam, S.; Lam, C.; Phu, L.; Phung, Q.; Maurer, B.; Arnott, D.; Kirkpatrick, D.S.; Dixit, V.M.; Hymowitz, S.G.

  • Improved quantitative mass spectrometry methods for characterizing complex ubiquitin signals.

    Molecular & Cellular Proteomics, 2010, ISSN: 1535-9484

    Phu, L.; Izrael, T.A.; Matsumoto, M.L.; Bustos, D.J.; Dynek, J.N.; Fedorova, A.V.; Bakalarski, C.E.; Arnott, D.; Deshayes, K.; Dixit, V.M.; Kelley, R.F.; Vucic, D.; Kirkpatrick, D.S.

  • Characterization of Intestinal Gene Expression Profiles in Crohn's Disease by Genome-wide Microarray Analysis.

    Inflammatory Bowel Diseases, 2010, ISSN: 1078-0998

    Noble, C.; Abbas, A.R.; Lees, C.W.; Cornelius, J.; Toy, K.; Modrusan, Z.; Clark, H.F.; Arnott, I.D.; Penman, I.D.; Satsangi, J.; Diehl, L.

  • Proteomic profiling of cancer-opportunities, challenges, and context.

    The Journal of Pathology, 2010, ISSN: 1096-9896

    Arnott, D.; Emmert-Buck, M.

  • Template Proteogenomics: Sequencing Whole Proteins Using an Imperfect Database.

    Molecular and Cellular Proteomics, 2010, ISSN: 1535-9476

    Castellana, N.; Pham, V.; Arnott, D.; Lill, J.; Bafna, V.

  • Autophosphorylated CaMKIIα Acts as a Scaffold to Recruit Proteasomes to Dendritic Spines.

    Cell, 2010, ISSN: 0092-8674

    Bingol, B.; Wang, C.F.; Arnott, D.; Cheng, D.M.; Peng, J.M.; Sheng, M.

  • Targeting interferon alpha subtypes in serum: a comparison of analytical approaches to the detection and quantitation of proteins in complex biological matrices.

    Journal of Proteome Research, 2009, ISSN: 1535-3893

    Izrael-Tomasevic, A.; Phu, L.; Phung, Q.T.; Lill, J.R.; Arnott, D.

  • Association of C-terminal ubiquitin hydrolase BRCA1-associated protein 1 with cell cycle regulator host cell factor 1.

    Molecular & Cellular Biology, 2009, ISSN: 1098-5549

    Misaghi, S.; Ottosen, S.; Izrael-Tomasevic, A.; Arnott, D.; Lamkanfi, M.; Lee, J.; Liu, J; O'Rourke, K.; Dixit, V.M.; Wilson, A.C.

  • B and T lymphocyte attenuator regulates B cell receptor signaling by targeting Syk and BLNK.

    Journal of Immunology, 2009, ISSN: 0022-1767

    Vendel, A.C.; Calemine-Fenaux, J.; Izrael-Tomasevic, A.; Chauhan, V.; Arnott, D.; Eaton, D.L.

  • Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2¹.

    Biochemical Journal, 2009, ISSN: 1470-8728

    Blankenship, J.W.; Varfolomeev, E.; Goncharov, T.; Fedorova, A.V.; Kirkpatrick, D.S.; Izrael-Tomasevic, A.; Phu, L.; Arnott, D.; Aghajan, M.; Zobel, K.; Bazan, J.F.; Fairbrother, W.J.; Deshayes, K.; Vucic, D.

• Education
  • University of Virginia, Chemistry, Ph.D. – 1994
  • Genentech Inc., Protein Chemistry Postdoctoral Fellow – 1994-1997
  • University of Delaware, Chemistry, B.S. – 1989
  • University of Delaware, Philosophy, B.A. – 1989