Wayne Fairbrother

Director, Staff Scientist, Early Discovery Biochemistry

POSTDOC MENTOR

"At Genentech I am surrounded by many dedicated scientists and technicians with the common goal of discovering and developing novel therapeutics to treat important human diseases."

• 21
  years at Genentech
• 23
  publications (2010-12)
• 3
  awards & honors

I joined Genentech in 1992 and, together with Nick Skelton, established a Protein Nuclear Magnetic Resonance (NMR) group that focuses primarily on the application of techniques for studying the solution structures of proteins and protein-protein or protein-ligand complexes of therapeutic interest.

I am currently Director of the Protein Engineering department. I was originally attracted to Genentech by the highly collaborative research environment, in general, and the scientists in the Protein Engineering department, in particular, who were dedicated to investigating important protein structure/function and molecular recognition problems.

• My Focus

  In the past I have contributed structural biology support to a number of projects aimed at characterizing important protein-peptide interactions. More recently I have had leadership roles in multi-disciplinary projects in which structure-based design was used to identifying small-molecule antagonists of protein-protein interactions. Small molecules resulting from these efforts are currently being tested in clinical trials.

  I now lead a department whose focus is exploring novel protein targets through the use of biophysical, biochemical, chemical and structural-biology methods, developing tools to pharmacologically validate novel targets, and the develop technologies to target challenging proteins.

• Publications

  • Bcl-2/Bcl-xL Inhibition Increases the Efficacy of Mek Inhibition Alone and in Combination with PI3 Kinase Inhibition in Lung and Pancreatic Tumor Models

    Molecular Cancer Therapeutics, 2013, ISSN: 1535-7163

    Tan, Nguyen; Wong, Maureen; Nannini, Michelle A; Hong, Rebecca; Lee, Leslie B; Price, Stephen; Williams, Karen; Savy, Pierre Pascal; Yue, Peng; Sampath, Deepak; Settleman, Jeffrey; Fairbrother, Wayne J; Belmont, Lisa D

     View on PubMed

  • ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

    Nature Medicine, 2013, ISSN: 1078-8956

    Souers, Andrew J.; Leverson, Joel D.; Boghaert, Erwin R.; Ackler, Scott L.; Catron, Nathaniel D.; Chen, Jun; Dayton, Brian D.; Ding, Hong; Enschede, Sari H.; Fairbrother, Wayne J.; Huang, David C. S.; Hymowitz, Sarah G.; Jin, Sha; Khaw, Seong Lin; Kovar, Peter J.; Lam, Lloyd T.; Lee, Jackie; Maecker, Heather L.; Marsh, Kennan C.; Mason, Kylie D.; Mitten, Michael J.; Nimmer, Paul M.; Oleksijew, Anatol; Park, Chang H.; Park, Cheol-Min; Phillips, Darren C.; Roberts, Andrew W.; Sampath, Deepak; Seymour, John F.; Smith, Morey L.; Sullivan, Gerard M.; Tahir, Stephen K.; Tse, Chris; Wendt, Michael D.; Xiao, Yu; Xue, John C.; Zhang, Haichao; Humerickhouse, Rod A.; Rosenberg, Saul H.; Elmore, Steven W.

     View on PubMed

  • Toxicity Profile of Small-Molecule IAP Antagonist GDC-0152 is Linked to TNF-ALPHA Pharmacology

    Toxicological Sciences, 2012, ISSN: 1096-0929

    Erickson, Rebecca Ida; Tarrant, Jacqueline; Cain, Gary; Lewin-Koh, Sock-Cheng; Dybdal, Noel; Wong, Harvey; Blackwood, Elizabeth; West, Kristina; Steigerwalt, Ronald; Mamounas, Michael; Flygare, John A; Amemiya, Kenjie; Dambach, Donna; Fairbrother, Wayne J; Diaz, Dolores

     View on PubMed

  • Characterization of ML-IAP protein stability and physiological role in vivo

    Biochemical Journal, 2012, ISSN: 0264-6021

    Varfolomeev, Eugene; Moradi, Elham; Dynek, Jasmin N.; Zha, Jiping; Fedorova, Anna V.; Deshayes, Kurt; Fairbrother, Wayne J.; Newton, Kim; Le Couter, Jennifer; Vucic, Domagoj

     View on PubMed

  • Navitoclax (ABT-263) Reduces Bcl-x(L)-Mediated Chemoresistance in Ovarian Cancer Models

    Molecular Cancer Therapeutics, 2012, ISSN: 1535-7163

    Wong, Maureen; Tan, Nguyen; Zha, Jiping; Peale, Franklin V; Yue, Peng; Fairbrother, Wayne J; Belmont, Lisa D;

     View on PubMed

  • Discovery of a Potent Small-Molecule Antagonist of Inhibitor of Apoptosis (IAP) Proteins and Clinical Candidate for the Treatment of Cancer (GDC-0152)

    Journal of Medicinal Chemistry, 2012, ISSN: 0022-2623

    Flygare, John A; Beresini, Maureen; Budha, Nageshwar; Chan, Helen; Chan, Iris T; Cheeti, Sravanthi; Cohen, Frederick; Deshayes, Kurt; Doerner, Karl; Eckhardt, S. Gail; Elliott, Linda O; Feng, Bainian; Franklin, Matthew C; Reisner, Stacy Frankovitz; Gazzard, Lewis; Halladay, Jason; Hymowitz, Sarah G; La, Hank; LoRusso, Patricia; Maurer, Brigitte; Murray, Lesley; Plise, Emile; Quan, Clifford; Stephan, Jean-Philippe; Young, Shin G; Tom, Jeffrey; Tsui, Vickie; Um, Joanne; Varfolomeev, Eugene; Vucic, Domagoj; Wagner, Andrew J; Wallweber, Heidi J. A; Wang, Lan; Ware, Joseph; Wen, Zhaoyang; Wong, Harvey; Wong, Jonathan M; Wong, Melisa; Wong, Susan; Yu, Ron; Zobel, Kerry; Fairbrother, Wayne J;

     View on PubMed

  • The structure of the extracellular domain of the jumping translocation breakpoint protein reveals a variation of the midkine fold

    Journal of Molecular Biology, v415(1), p22-28, ISSN: 1089-8638

    Rousseau, Francois; Fairbrother, Wayne J.; Bazan, J. Fernando; Lingel, Andreas; Pan, Borlan

     View on PubMed

  • Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.

    Science, 21 Oct 2011, vol. 334, no. 6054, p. 376-80, ISSN: 1095-9203.

    Dueber, Erin C; Schoeffler, Allyn J; Lingel, Andreas; Elliott, J Michael; Fedorova, Anna V; Giannetti, Anthony M; Zobel, Kerry; Maurer, Brigitte; Varfolomeev, Eugene; Wu, Ping; Wallweber, Heidi J A; Hymowitz, Sarah G; Deshayes, Kurt; Vucic, Domagoj; Fairbrother, Wayne J

     View on PubMed

  • Murine Insulin Growth Factor-like (IGFL) and Human IGFL1 Proteins Are Induced in Inflammatory Skin Conditions and Bind to a Novel Tumor Necrosis Factor Receptor Family Member, IGFLR1.

    JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, V286, N21, MAY 27, pp 18969-18981. ISSN: 0021-9258.

    Lobito, Adrian A; Ramani, Sree R; Tom, Irene; Bazan, J Fernando; Luis, Elizabeth; Fairbrother, Wayne J; Ouyang, Wenjun; Gonzalez, Lino C

  • Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity.

    Journal of Medicinal Chemistry, 2011, ISSN: 0022-2623

    Sleebs, B.E.; Czabotar, P.E.; Fairbrother, W.J.; Fairlie, W.D.; Flygare, J.A.; Huang, D.C.S.; Kersten, W.J.A.; Koehler, M.F.T.; Lessene, G.; Lowes, K.; Parisot, J.P.; Smith, B.J.; Smith, M.L.; Souers, A.J.; Street, I.P.; Yang, H.; Baell, J.B.

  • 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.

  • Navitoclax Enhances the Efficacy of Taxanes in Non-Small Cell Lung Cancer Models.

    Clinical Cancer Research, 2011, ISSN: 1078-0432

    Tan, N.; Malek, M.; Zha, J.; Kassees, R.; Yue, P.; Berry, L.; Fairbrother, W.; Sampath, D.; Belmont, L.

  • c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling.

    EMBO Journal, 2010, ISSN: 1460-2075

    Dynek, J.N.; Goncharov, T.; Dueber, E.C.; Fedorova, A.V.; Izrael-Tomasevic, A.; Phu, L.; Helgason, E.; Fairbrother, W.J.; Deshayes, K.; Kirkpatrick, D.S.; Vucic, D.

  • Preclinical Pharmacokinetic Assessment of GDC-0152, a Selective Antagonist of the Inhibitor of Apoptosis (IAP) Proteins.

    Drug Metabolism Reviews, 2010, ISSN: 0360-2532

    La, H.; Halladay, J.S.; Shin, Y.; Wong, S.; Plise, E.; Chan, O.H.; Flygare, J.; Fairbrother, W.; Wong, H.

  • Antagonists of inhibitor of apoptosis proteins based on thiazole amide isosteres.

    Bioorganic & Medicinal Chemistry Letters, 2010, ISSN: 1464-3405

    Cohen, F.; Koehler, M.; Bergeron, P.; Elliott, L.; Flygare, J.; Franklin, M.; Gazzard, L.; Keteltas, S.; Lau, K.; Ly, C.; Tsui, V.; Fairbrother, W.

  • Small-molecule pan-IAP antagonists: a patent review.

    Expert Opinion on Therapeutic Patents, 2010, ISSN: 1744-7674

    Flygare, J.A.; Fairbrother, W.J.

  • Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors: insight into heterotrimeric IL-1 signaling complexes.

    Structure, 2009, ISSN: 1878-4186

    Lingel, A.; Weiss, T.M.; Niebuhr, M.; Pan, B.; Appleton, B.A.; Wiesmann, C.; Bazan, J.F.; Fairbrother, W.J.

  • X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists.

    Journal of Biological Chemistry, 2009, ISSN: 1083-351X

    Varfolomeev, E.; Alicke, B.; Elliott, J.M.; Zobel, K.; West, K.; Wong, H.; Scheer, J.M.; Ashkenazi, A.; Gould, S.E.; Fairbrother, W.J.; Vucic, D.

  • Phosphorylation of a borealin dimerization domain is required for proper chromosome segregation.

    Biochemistry, 2009, ISSN: 1520-4995

    Bourhis, E.; Lingel, A.; Phung, Q.; Fairbrother, W.J.; Cochran, A.G.

  • Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists.

    ACS Chemical Biology [Electronic Resource], 2009, ISSN: 1554-8937

    Ndubaku, C.; Varfolomeev, E.; Wang, L.; Zobel, K.; Lau, K.; Elliott, L.O.; Maurer, B.; Fedorova, A.V.; Dynek, J.N.; Koehler, M.; Hymowitz, S.G.; Tsui, V.; Deshayes, K.; Fairbrother, W.J.; Flygare, J.A.; Vucic, D.

  • 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.

  • c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor α (TNFα)-induced NF-κB Activation.

    Journal of Biological Chemistry, 2008, ISSN: 0021-9258

    Varfolomeev, E.; Goncharov, T.; Fedorova, A.V.; Dynek, J.N.; Zobel, K.; Deshayes, K.; Fairbrother, W.J.; Vucic, D.

  • Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas.

    Cancer Research, 2008, ISSN: 1538-7445

    Dynek, J.N.; Chan, S.M.; Liu, J.; Zha, J.; Fairbrother, W.J.; Vucic, D.

• Education
  • The Scripps Research Institute, Department of Molecular Biology, Postdoctoral Fellow – 1992
  • Oxford University, United Kingdom, Inorganic Chemistry Laboratory, D.Phil. – 1989
  • University of Otago, New Zealand, Department of Chemistry, B.Sc. – 1984
• Awards & Honors
  • Damon Runyon-Walter Winchell Cancer Research Fund Postdoctoral Fellowship – 1990-1992
  • Wolfson College Graduate Award – 1987-1999
  • Commonwealth Scholarship – 1986-1989