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Scientist Profile

Wayne Fairbrother

Director, Staff Scientist: Early Discovery Biochemistry
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"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."
 

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.

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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.

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Publications & Recognition
  • The structure of the extracellular domain of the Jumping Translocation Breakpoint protein reveals a variation of the Midkine fold.
  • J. Mol. Biol. 415, 22-28.
  • F. Rousseau, B. Pan, W.J. Fairbrother, J.F. Bazan, and A. Lingel.
  • Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.
  • Science 334, 376-380.
  • E.C. Dueber, A.J. Schoeffler, A. Lingel, J.M. Elliott, A.V. Fedorova, A.M. Giannetti, K. Zobel, B. Maurer, E. Varfolomeev, P. Wu, H.J. Wallweber, S.G. Hymowitz, K. Deshayes, D. Vucic, and W.J. Fairbrother.
  • 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.
  • J. Biol. Chem. 286, 18969-18981.
  • A.A. Lobito, S.R. Ramani, I. Tom. J.F. Bazan, E. Luis, W.J. Fairbrother, W. Ouyang, and L.C. Gonzalez.
 
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  • The Scripps Research Institute, Department of Molecular Biology
  • Postdoctoral Fellow
  • 1989-1992
  • Oxford University, United Kingdom, Inorganic Chemistry Laboratory
  • D.Phil.
  • 1986-1989
  • University of Otago, New Zealand, Department of Chemistry
  • B.Sc.
  • 1981-1984
Publications & Recognition
  • The structure of the extracellular domain of the Jumping Translocation Breakpoint protein reveals a variation of the Midkine fold.
  • J. Mol. Biol. 415, 22-28.
  • F. Rousseau, B. Pan, W.J. Fairbrother, J.F. Bazan, and A. Lingel.
  • Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.
  • Science 334, 376-380.
  • E.C. Dueber, A.J. Schoeffler, A. Lingel, J.M. Elliott, A.V. Fedorova, A.M. Giannetti, K. Zobel, B. Maurer, E. Varfolomeev, P. Wu, H.J. Wallweber, S.G. Hymowitz, K. Deshayes, D. Vucic, and W.J. Fairbrother.
  • 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.
  • J. Biol. Chem. 286, 18969-18981.
  • A.A. Lobito, S.R. Ramani, I. Tom. J.F. Bazan, E. Luis, W.J. Fairbrother, W. Ouyang, and L.C. Gonzalez.
  • Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.
  • Science. 2011 Oct 21; 334(6054): 376-80.
  • Dueber EC, Schoeffler AJ, Lingel A, Elliott JM, Fedorova AV, Giannetti AM, Zobel K, Maurer B, Varfolomeev E, Wu P, Wallweber HJ, Hymowitz SG, Deshayes K, Vucic D, Fairbrother WJ.
  • View Abstract on PubMed
  • X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists.
  • J Biol Chem 2009 Dec 11; 284(50): 34553-60.
  • Varfolomeev E, Alicke B, Elliott JM, Zobel K, West K, Wong H, Scheer JM, Ashkenazi A, Gould SE, Fairbrother WJ, Vucic D.
  • View Abstract on PubMed
  • Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes.
  • Structure 2009 Oct 14; 17(10): 1398-410.
  • Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, Bazan JF, Fairbrother WJ.
  • View Abstract on PubMed
  • Phosphorylation of a borealin dimerization domain is required for proper chromosome segregation.
  • Biochemistry 2009 Jul 28; 48(29): 6783-93.
  • Bourhis E, Lingel A, Phung Q, Fairbrother WJ, Cochran AG.
  • View Abstract on PubMed
  • Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists.
  • ACS Chem Biol 2009 Jul 17; 4(7): 557-66.
  • Ndubaku C, Varfolomeev E, Wang L, Zobel K, Lau K, Elliott LO, Maurer B, Fedorova AV, Dynek JN, Koehler M, Hymowitz SG, Tsui V, Deshayes K, Fairbrother WJ, Flygare JA, Vucic D.
  • View Abstract on PubMed
  • Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold.
  • J Med Chem 2009 Mar 26; 52(6): 1723-30.
  • Cohen F, Alicke B, Elliott LO, Flygare JA, Goncharov T, Keteltas SF, Franklin MC, Frankovitz S, Stephan JP, Tsui V, Vucic D, Wong H, Fairbrother WJ.
  • View Abstract on PubMed
  • Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1).
  • Biochem J 2009 Jan 1; 417(1): 149-60.
  • Blankenship JW, Varfolomeev E, Goncharov T, Fedorova AV, Kirkpatrick DS, Izrael-Tomasevic A, Phu L, Arnott D, Aghajan M, Zobel K, Bazan JF, Fairbrother WJ, Deshayes K, Vucic D.
  • View Abstract on PubMed
  • c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation.
  • J Biol Chem 2008 Sep 5; 283(36): 24295-9.
  • Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D.
  • View Abstract on PubMed
  • Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas.
  • Cancer Res 2008 May 1; 68(9): 3124-32.
  • Dynek JN, Chan SM, Liu J, Zha J, Fairbrother WJ, Vucic D.
  • View Abstract on PubMed
  • IAP antagonists induce auto-ubiquitination of cIAPs, NF-κB activation, and TNFα-dependent apoptosis.
  • Cell 131 2007; 669-681.
  • Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, Zobel K, Dynek JN, Elliott LO, Wallweber HJA, Flygare JA, Fairbrother WJ, Deshayes K, Dixit VM, Vucic D.
  • Structure of SAP18: a ubiquitin fold in histone deacetylase complex assembly.
  • Biochemistry 2006 Oct 3; 45(39): 11974-82.
  • McCallum SA, Bazan JF, Merchant M, Yin J, Pan B, de Sauvage FJ, Fairbrother WJ.
  • View Abstract on PubMed
  • The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF- kappaB activation independently of TRAF1 AND TRAF2.
  • J Biol Chem 2006 Sep 29; 281(39): 29022-9.
  • Varfolomeev E, Wayson SM, Dixit VM, Fairbrother WJ, Vucic D.
  • View Abstract on PubMed
  • Design, synthesis, and biological activity of a potent Smac mimetic that sensitizes cancer cells to apoptosis by antagonizing IAPs.
  • ACS Chem Biol 2006 Sep 19; 1(8): 525-33.
  • Zobel K, Wang L, Varfolomeev E, Franklin MC, Elliott LO, Wallweber HJ, Okawa DC, Flygare JA, Vucic D, Fairbrother WJ, Deshayes K.
  • View Abstract on PubMed
  • Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP.
  • Biochem J 2005 Jan 1; 385(Pt 1): 11-20.
  • Vucic D, Franklin MC, Wallweber HJ, Das K, Eckelman BP, Shin H, Elliott LO, Kadkhodayan S, Deshayes K, Salvesen GS, Fairbrother WJ.
  • View Abstract on PubMed
  • Convergent recognition of the IgE binding site on the high-affinity IgE receptor.
  • Structure 2004 Jul; 12(7): 1289-301.
  • Stamos J, Eigenbrot C, Nakamura GR, Reynolds ME, Yin J, Lowman HB, Fairbrother WJ, Starovasnik MA.
  • View Abstract on PubMed
  • Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP).
  • Biochemistry 2003 Jul 15; 42(27): 8223-31.
  • Franklin MC, Kadkhodayan S, Ackerly H, Alexandru D, Distefano MD, Elliott LO, Flygare JA, Mausisa G, Okawa DC, Ong D, Vucic D, Deshayes K, Fairbrother WJ.
  • View Abstract on PubMed
  • BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site.
  • Biochemistry 2003 May 27; 42(20): 5977-83.
  • Gordon NC, Pan B, Hymowitz SG, Yin J, Kelley RF, Cochran AG, Yan M, Dixit VM, Fairbrother WJ, Starovasnik MA.
  • View Abstract on PubMed
  • SMAC negatively regulates the anti-apoptotic activity of melanoma inhibitor of apoptosis (ML-IAP).
  • J Biol Chem 2002 Apr 5; 277(14): 12275-9.
  • Vucic D, Deshayes K, Ackerly H, Pisabarro MT, Kadkhodayan S, Fairbrother WJ, Dixit VM.
  • View Abstract on PubMed
  • Solution structure of a phage-derived peptide antagonist in complex with vascular endothelial growth factor.
  • J Mol Biol 2002 Feb 22; 316(3): 769-87.
  • Pan B, Li B, Russell SJ, Tom JY, Cochran AG, Fairbrother WJ.
  • View Abstract on PubMed
  • ICEBERG: a novel inhibitor of interleukin-1beta generation.
  • Cell 2000 Sep 29; 103(1): 99-111.
  • Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM.
  • View Abstract on PubMed
  • Novel peptides selected to bind vascular endothelial growth factor target the receptor-binding site.
  • Biochemistry 1998 Dec 22; 37(51): 17754-64.
  • Fairbrother WJ, Christinger HW, Cochran AG, Fuh G, Keenan CJ, Quan C, Shriver SK, Tom JY, Wells JA, Cunningham BC.
  • View Abstract on PubMed
  • Backbone dynamics of the EGF-like domain of heregulin-alpha. .
  • J Mol Biol 1998 Jun 26; 279(5): 1149-61.
  • Fairbrother WJ, Liu J, Pisacane PI, Sliwkowski MX, Palmer AG 3rd.
  • View Abstract on PubMed
  • Solution structure of the heparin-binding domain of vascular endothelial growth factor.
  • Structure 1998 May 15; 6(5): 637-48.
  • Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA.
  • View Abstract on PubMed
  • Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase.
  • Nat Struct Biol 1998 Jan; 5(1): 47-54.
  • Gitschier J, Moffat B, Reilly D, Wood WI, Fairbrother WJ.
  • View Abstract on PubMed
  • Solution structure of the E-domain of staphylococcal protein A.
  • Biochemistry 1996 Dec 3; 35(48): 15558-69.
  • Starovasnik MA, Skelton NJ, O'Connell MP, Kelley RF, Reilly D, Fairbrother WJ.
  • View Abstract on PubMed
  • Exchanging interleukin-8 and melanoma growth-stimulating activity receptor binding specificities.
  • J Biol Chem 1996 Jun 14; 271(24): 14344-52.
  • Lowman HB, Slagle PH, DeForge LE, Wirth CM, Gillece-Castro BL, Bourell JH, Fairbrother WJ.
  • View Abstract on PubMed
  • High-resolution solution structure of the EGF-like domain of heregulin-alpha.
  • Biochemistry 1996 Mar 19; 35(11): 3402-17.
  • Jacobsen NE, Abadi N, Sliwkowski MX, Reilly D, Skelton NJ, Fairbrother WJ.
  • View Abstract on PubMed
  • Minimization of a polypeptide hormone.
  • Science 1995 Dec 8; 270(5242): 1657-60.
  • Li B, Tom JY, Oare D, Yen R, Fairbrother WJ, Wells JA, Cunningham BC.
  • View Abstract on PubMed
  • The solution structure of melanoma growth stimulating activity.
  • J Mol Biol 1994 Sep 23; 242(3): 252-70.
  • Fairbrother WJ, Reilly D, Colby TJ, Hesselgesser J, Horuk R.
  • View Abstract on PubMed
  • A novel isotope labeling protocol for bacterially expressed proteins.
  • J Biomol NMR 1994 May; 4(3): 459-62.
  • Reilly D, Fairbrother WJ.
  • View Abstract on PubMed
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Awards & Honors
  • Damon Runyon-Walter Winchell Cancer Research Fund Postdoctoral Fellowship--1990-1992
  • Wolfson College Graduate Award--1987-1999
  • Commonwealth Scholarship, Wolfson College, Oxford, U.K.--1986-1989

Wayne Fairbrother, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.