Ingrid Wertz

Scientist, Early Discovery Biochemistry

POSTDOC MENTOR

"Identifying subtle variations that promote significant biological consequences has always fascinated me. The key is to distinguish which small changes matter and which ones don't; this knowledge can then facilitate the development of effective therapeutics."

• 7
  years at Genentech
• 18
  publications (2010-12)
• 10
  awards & honors

I began my career at Genentech as a graduate student in the laboratory of Vishva Dixit. During this time I had the opportunity to witness the transformation of scientific discoveries into therapeutic agents. In this way I learned that rigorous scientific experimentation is the foundation for rational drug design.

During my medical training I experienced how illness can transform the lives of patients and I saw first hand the impact that effective medicines can have in restoring their health. After completing my graduate and medical studies I chose to return to Genentech as a scientist in order to help patients through scientific discoveries. My aims are to understand the molecular basis of normal physiology and of disease and to translate those findings into novel therapeutics that benefit patients.

• My Focus

  My lab investigates protein alterations that promote human disease. These pathogenic changes may include aberrant enzymatic activity, altered protein expression levels, or post-translational modifications such as phosphorylation or ubiquitination. Oncoproteins, tumor suppressors, and components of homeostatic signaling cascades are often modified by such mechanisms. Thus improper regulation of proteins can promote inflammatory disorders, cancer, and other disease states.

  Our primary mission is to continue to identify and characterize the substrates and enzymes that regulate pathogenic signaling pathways. In this way, we aim to elucidate the molecular mechanisms by which aberrant protein modification contributes to disease. Our laboratory uses and develops a variety of molecular, cellular, genetic, biophysical, proteomic, and in vivo systems to achieve our research goals. As such we have active collaborations within our own department and also with other departments including Protein Chemistry, Research Oncology, Structural Biology, Antibody Engineering, Molecular Biology, and Pathology. Ultimately, our better understanding of the pathogenesis of human disease may be translated to the benefit of patients by revealing critical diagnostic markers and disease targets for pharmacological intervention.

• Publications

  • HectD1 E3 Ligase Modifies Adenomatous Polyposis Coli (APC) with Polyubiquitin to Promote the APC-Axin Interaction

    The Journal of biological chemistry, 2012, ISSN: 0021-9258

    Tran, Hoanh; Bustos, Daisy; Yeh, Ronald; Rubinfeld, Bonnee; Lam, Cynthia; Shriver, Stephanie; Zilberleyb, Inna; Lee, Michelle W; Phu, Lilian; Sarkar, Anjali A; Zohn, Irene E; Wertz, Ingrid E; Kirkpatrick, Donald S; Polakis, Paul

     View on PubMed

  • Conformational stabilization of ubiquitin yields potent and selective inhibitors of USP7

    Nature Chemical Biology, 2012, ISSN: 1552-4450

    Zhang, Yingnan; Zhou, Lijuan; Rouge, Lionel; Phillips, Aaron H; Lam, Cynthia; Liu, Peter; Sandoval, Wendy; Helgason, Elizabeth; Murray, Jeremy M; Wertz, Ingrid E; Corn, Jacob E

     View on PubMed

  • It takes two to tango: a new couple in the family of ubiquitin-editing complexes

    Nature Immunology, 16 Nov 2011, vol.12, no.12, p.1133-5, ISSN: 1529-2916

    Wertz, Ingrid E

     View on PubMed

  • Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death.

    Nature reviews. Molecular cell biology, {Nat-Rev-Mol-Cell-Biol}, 2011 (epub), vol. 12, no. 7, p. 439-52, ISSN: 1471-0080.

    Vucic, Domagoj; Dixit, Vishva M; Wertz, Ingrid E

     View on PubMed

  • 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

  • Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7.

    Nature, 2011, ISSN: 0028-0836

    Wertz, I.E.; Kusam, S.; Lam, C.; Okamoto, T.; Sandoval, W.; Anderson, D.J.; Helgason, E.; Ernst, J.A.; Eby, M.; Liu, J.; Belmont, L.D.; Kaminker, J.S.; O'Rourke, K.M.; Pujara, K.; Kohli, P.B.; Johnson, A.R.; Chiu, M.L.; Lill, J.R.; Jackson, P.K.; Fairbrother, W.J.; Seshagiri, S.; Ludlam, M.J.C.; Leong, K.G.; Dueber, E.C.; Maecker, H.; Huang, D.C.S.; Dixit, V.M.

  • 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.

  • A20: from ubiquitin editing to tumour supression

    Nature Reviews Cancer, 2010, ISSN: 1474-1768

    Hymowitz, S.G.; Wertz, I.E.

  • Signaling to NF-_KB: Regulation by Ubiquitination.

    Cold Spring Harbor Perspectives in Biology, 2010, ISSN: 1943-0264

    Wertz, I.E.; Dixit, V.M.

  • Regulation of death receptor signaling by the ubiquitin system.

    Cell Death and Differentiation, {Cell-Death-Differ}, January 2010, vol. 17, no. 1, p. 14-24, 115 refs, CODEN: CDDIE, eISSN: 1476-5403, ISSN: 1350-9047. Publisher: Nature Publishing Group, Houndmills, Basingstoke, Hampshire, RG21 6XS, UK.

    Wertz, IE; Dixit, VM

     View on PubMed

  • Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies.

    Cell, 2008, ISSN: 1097-4172

    Newton, K; Matsumoto, M.L.; Wertz, I.E.; Kirkpatrick, D.S.; Lill, J.R.; Tan, J.; Dugger, D.; Gordon, N.; Sidhu, S.S,; Fellouse, F.A.; Komuves, L.; French, D.M.; Ferrando, R.E.; Lam, C.; Compaan, D.; Yu, C.; Bosanac, I.; Hymowitz, S.G.; Kelley, R.F.; Dixit, V.M.

  • Ubiquitin-mediated regulation of TNFR1 signaling.

    Cytokine & Growth Factor Reviews, 2008, ISSN: 1359-6101

    Wertz, I.E; Dixit, V.M.

  • Targeted mass spectrometric strategy for global mapping of ubiquitination on proteins

    Rapid Communications in Mass Spectrometry, 2007, ISSN:

    Mollah, S.; Wertz, I.E.; Phung, Q.; Arnott, D.; Dixit, V.M.; Lill, J.R.

  • Yersinia virulence factor YopJ acts as a deubiquitinase to inhibit NF-κB activation

    J. Exp. Med., 2005, ISSN:

    Zhou, H.;Monack, D.M.;Kayagaki, N.;Wertz, I.;Yin, J.;Wolf, B.;Dixit, V.M.

  • De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κ B signaling

    Nature, 2004, ISSN:

    Wertz, I.E.;O'Rourke, K.M.;Zhou, H.;Eby, M.;Aravind, L.;Seshagiri, S.;Wu, P.;Wiesmann, C.;Baker, R.;Boone, D.L.;Ma, A.;Koonin, E.V.;Dixit, V.M.

  • The ubiquitin ligase COP1 is a critical negative regulator of p53

    Nature, 2004, ISSN:

    Dornan, D.;Wertz, I.;Shimizu, H.;Arnott, D.;Frantz, G.D.;Dowd, P.;O'Rourke, K.;Koeppen, H.;Dixit, V.M.

  • Human de-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase

    Science, 2004, ISSN:

    Wertz, I.E.;O'Rourke, K.M.;Zhang, Z.;Dornan, D.;Arnott, D.;Deshaies, R.J.;Dixit, V.M.

  • Bcl10 activates the NF-κB pathway through ubiquitination of NEMO

    Nature, 2004, ISSN:

    Zhou, H.;Wertz, I.;O'Rourke, K.;Ultsch, M.;Seshagiri, S.;Eby, M.;Xiao, W.;Dixit, V.M.

• Education
  • Washington University, St. Louis, MO, M.D. – 2006
  • University of California, Davis, CA, Ph.D. – 2004
  • Genentech, Inc., South San Francisco, CA, Visiting Scientist – 1998 - 2004
  • University of California, Berkeley, CA, B.A. – 1992
• Awards & Honors
  • Harold M. Weintraub Graduate Research Award, Fred Hutchinson Cancer Research Center, Seattle, WA – 2005
  • Morton Levitt Research Award – 2005
  • Genentech Postdoctoral Offsite First Place Research Award – 2004
  • Washington University, St. Louis, Medical Scientist Training Program Fellowship – 2004-2006
  • Genentech Postdoctoral Offsite First Place Research Award – 2002
  • Alza Pharmaceuticals Research Award – 1997
  • NIH Biotechnology Training Grant – 1996-1999
  • Pro Femina Research Consortium Research Award – 1996
  • U.C. Davis Physician Scientist Training Program Fellowship – 1996-2004
  • Phi Sigma Honor Society – 1995