/ Scientists I have been at Genentech since 1996. After training in bio-organic chemistry and in protein biophysics, I wanted to combine these fields. The Protein Engineering department at Genentech is uniquely committed to investigating basic protein structure-function questions and, in particular, to understanding molecular recognition between proteins and between proteins and smaller molecules. Projects in my lab involve diverse approaches to understanding proteins and protein complexes with the organizing theme of novel target or lead discovery in areas relevant to cancer. Many interesting potential targets are protein-protein interactions. However, these are not considered traditionally 'druggable' and often do not yield useful 'hits' in high-throughput screens. Past projects have therefore explored minimal requirements for protein-protein and protein-peptide recognition to better understand which targets may be tractable. Work in this area led us to study individual residue contributions to strand-strand recognition in ?-sheet proteins. These studies initially involved structural stability assays in peptides, leading to the design of a family of very small and stably folded ?-hairpins (tryptophan zippers). To extend our work to larger proteins, we developed a quantitative phage display method to probe cross-strand residue pairing in ?-sheets. More recently, the lab has been focused on the biochemistry and cellular function of mitotic protein kinases. We have probed activation mechanisms and cellular function by site-directed mutagenesis and applied phage display and truncation mutagenesis to define structurally important regions of reported binding partners. These subdomains are excellent starting points for structural studies by NMR or x-ray crystallography. Finally, we have employed proteomic techniques (affinity purification/mass spectrometry and yeast two-hybrid methods) to discover new binding partners and fit them into pathways. We are now starting new projects in the areas of epigenetic modifications and deubiquitinases.

• My Focus

  I collaborate extensively with structural biologists in Protein Engineering, medicinal chemists, and with colleagues in the Oncology and Cell Cycle areas. Projects in my lab involve diverse approaches to understanding proteins and protein complexes with the organizing theme of novel target or lead discovery in areas relevant to cancer. My long-term goal is to understand as much as possible about protein structure and function from a chemical perspective but more importantly, to apply this perspective to challenging biological problems.

• Publications

  • 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

  • Wnt Antagonists Bind through a Short Peptide to the First beta-Propeller Domain of LRP5/6.

    Structure, 21 Sep 2011, ISSN: 1878-4186.

    Bourhis, Eric; Wang, Weiru; Tam, Christine; Hwang, Jiyoung; Zhang, Yingnan; Spittler, Didier; Huang, Oscar W; Gong, Yan; Estevez, Alberto; Zilberleyb, Inna; Rouge, Lionel; Chiu, Cecilia; Wu, Yan; Costa, Mike; Hannoush, Rami N; Franke, Yvonne; Cochran, Andrea G

     View on PubMed

  • Recognition of UbcH5c and the nucleosome by the Bmi1/Ring1b ubiquitin ligase complex

    The EMBO journal, {EMBO-J}, 19 Jul 2011 (epub: 19 7 2011), ISSN: 1460-2075.

    Bentley, Matthew L; Corn, Jacob E; Dong, Ken C; Phung, Qui; Cheung, Tommy K; Cochran, Andrea G

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  • Reconstitution of a Frizzled8^.Wnt₃a^.LRP6 Signaling Complex Reveals Multiple Wnt and Dkk1 Binding Sites on LRP6.

    Journal of Biological Chemistry, 2010, ISSN: 1083-351X

    Bourhis, E.; Tam, C.; Franke, Y.; Bazan, J.F.; Ernst, J.; Hwang, J.; Costa, M.; Cochran, A.G.; Hannoush, R.N.

  • 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.

  • A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high selectivity against Aurora B.

    Journal of Medicinal Chemistry, 2009, ISSN: 1520-4804

    Aliagas-Martin, I.; Burdick, D.; Corson, L.; Dotson, J.; Drummond, J.; Fields, C.; Huang, O.W.; Hunsaker. T.; Kleinheinz, T.; Krueger, E.; Liang, J.; Moffat, J.; Phillips, G.; Pulk, R.; Rawson, T.E.; Ultsch, M.; Walker, L.; Wiesmann, C.; Zhang, B.; Zhu, B.Y.; Cochran, A.G.

  • Stability of cyclic β-hairpins: asymmetric contributions from side chains of a hydrogen-bonded cross-strand residue pair

    J. Amer. Chem. Soc., 2003, ISSN:

    Russell, S.J.;Blandl, T.;Skelton, N.J.;Cochran, A.G.

• Education
  • Whitehead Institute for Biomedical Research, Postdoctoral Fellow – 1996
  • University of California, Berkeley, Department of Chemistry, Ph.D. – 1992
  • Massachusetts Institute of Technology, Department of Chemistry, B.S. – 1986
• Awards & Honors
  • National Science Foundation Postdoctoral Fellow – 1992
  • Schering-Plough Fellow – 1989