I came to Genentech in 2004 to extend my research focus from signal transduction genetics in invertebrate model systems to cancer pathways biology.

I feel that the critical mass of talented scientists and valuable resources at Genentech provides a research environment uniquely suited to uncovering how complex, interacting signaling pathways and their components drive human diseases. Importantly, Genentech also has the expertise and infrastructure to efficiently advance early-stage research discoveries into clinical development of targeted therapies, and through to marketed products that benefit patients.

• My Focus

  My research group is focused on developing mechanism-based therapies targeting Wnt/?-catenin signaling, which is aberrantly activated at different points in the pathway at high incidence in many tumor types. We are pursuing diverse approaches to inhibit specific components of the pathway using monoclonal antibodies and small molecules.

  Additionally, we are identifying new Wnt signaling components in genetic screens and defining their molecular mechanisms and pathway interactions that mediate or modify ?-catenin activity. Finally, we are utilizing the research tools developed from these studies to better understand the different ways in which activated Wnt signaling initiates tumorigenesis and is required for tumor progression in different cancers.

• Publications

  • A Novel Tankyrase Small-molecule Inhibitor Suppresses APC Mutation-driven Colorectal Tumor Growth

    Cancer Research, 2013, ISSN: 0008-5472

    Lau, Ted; Chan, Emily; Callow, Marinella; Waaler, Jo; Boggs, Jason; Blake, Robert A; Magnuson, Steven; Sambrone, Amy; Schutten, Melissa; Firestein, Ron; Machon, Ondrej; Korinek, Vladimir; Choo, Edna; Diaz, Dolores; Merchant, Mark; Polakis, Paul; Holsworth, Daniel D; Krauss, Stefan; Costa, Mike

     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

  • Ubiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling

    PLoS ONE, {PLoS-ONE}, 2011, vol. 6, no. 7, article number: e22595, 35 refs, eISSN: 1932-6203. Publisher: Public Library of Science, 185 Berry Street, Suite 1300, San Francisco, CA 94107, USA.

    Callow, Marinella G; Tran, Hoanh; Phu, Lilian; Lau, Ted; Lee, James; Sandoval, Wendy N; Liu, Peter S; Bheddah, Sheila; Tao, Janet; Lill, Jennie R; Hongo, Jo Anne; Davis, David; Kirkpatrick, Donald S; Polakis, Paul; Costa, Mike

     View on PubMed

  • Wnt Isoform-Specific Interactions with Coreceptor Specify Inhibition or Potentiation of Signaling by LRP6 Antibodies.

    PloS ONE, 2010, ISSN: 1932-6203

    Gong, Y.; Bourhis, E.; Chiu, C.; Stawicki, S.; DeAlmeida, V.; Liu, B.; Phamluong, K.; Cao, T.; Carano, R.; Ernst, J.; Solloway, M.; Rubinfeld, B.; Hannoush, R.; Wu, Y.; Polakis, P.; Costa, M.

  • 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.

  • TSPAN12 regulates retinal vascular development by promoting Norrin but not Wnt-induced FZD4/β-catenin signaling.

    Cell, 2009, ISSN: 1097-4172

    Junge, H.J.; Yang, S.; Burton, J.B.; Paes, K.; Shu, X.; French, D.M.; Costa, M.; Rice, D.S.; Ye, W.

  • Inhibition of Wnt signaling by Dishevelled PDZ peptides.

    Nature Chemical Biology, 2009, ISSN: 1552-4469

    Zhang, Y.; Appleton, B.A.; Wiesmann, C.; Lau, T.; Costa, M.; Hannoush, R.N.; Sidhu, S.S.

• Education
  • Fred Hutchinson Cancer Research Center, Postdoctoral Fellow – 1997
  • Fred Hutchinson Cancer Research Center, Postdoctoral Fellow – 1997
  • Princeton University, Department of Molecular Biology, Ph.D. – 1994
  • Princeton University, Department of Molecular Biology, Ph.D. – 1994
  • Princeton University, Department of Molecular Biology, Ph.D. – 1994
  • Princeton University, Department of Molecular Biology, Ph.D. – 1994
  • Cornell University, Department Biological Sciences, B.S. – 1986
  • Cornell University, Department Biological Sciences, B.S. – 1986
  • Cornell University, Department Biological Sciences, B.S. – 1986
  • Cornell University, Department Biological Sciences, B.S. – 1986
  • University of California, San Francisco, Research Associate – 1984
  • University of California, San Francisco, Research Associate – 1984
• Awards & Honors
  • Damon Runyon-Walter Winchell Foundation Postdoctoral Fellowship – 1994
  • Damon Runyon-Walter Winchell Foundation Postdoctoral Fellowship – 1994
  • Card Family Fund Dissertation Travel Research Award – 1986
  • Card Family Fund Dissertation Travel Research Award – 1986