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Scientist Profile

Mike Costa

Senior Scientist, Discovery Oncology
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"I am inspired by my daily interactions here with like-minded scientists driven by a passion for discovery and commitment to translating a deeper understanding of biologic processes into novel disease therapies."
 

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.

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My Focus

My research group is focused on developing mechanism-based therapies targeting Wnt/β-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 β-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.

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Publications & Recognition
  • Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6.
  • J Biol Chem 2010 Mar 19; 285(12): 9172-9.
  • Bourhis E, Tam C, Franke Y, Bazan JF, Ernst J, Hwang J, Costa M, Cochran AG, Hannoush RN.
  • View Abstract on PubMed
  • TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling.
  • Cell 2009 Oct 16; 139(2): 299-311.
  • Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W.
  • View Abstract on PubMed
  • Inhibition of Wnt signaling by Dishevelled PDZ peptides.
  • Nat Chem Biol. 2009 Apr; 5(4): 217-9.
  • Zhang Y, Appleton BA, Wiesmann C, Lau T, Costa M, Hannoush RN, Sidhu SS.
  • View Abstract on PubMed
 
View All Publications & Recognition
 
  • Princeton University, Department of Molecular Biology
  • Ph.D.
  • 1988-1994
  • Cornell University, Department Biological Sciences
  • B.S.
  • 1982-1986
  • Fred Hutchinson Cancer Research Center
  • Postdoctoral Fellow
  • 1994-1997
  • Princeton University, Department of Molecular Biology
  • Ph.D.
  • 1988-1994
  • University of California, San Francisco
  • Research Associate
  • 1986-19884
  • Cornell University, Department Biological Sciences
  • B.S.
  • 1982-1986
Publications & Recognition
  • Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6.
  • J Biol Chem 2010 Mar 19; 285(12): 9172-9.
  • Bourhis E, Tam C, Franke Y, Bazan JF, Ernst J, Hwang J, Costa M, Cochran AG, Hannoush RN.
  • View Abstract on PubMed
  • TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling.
  • Cell 2009 Oct 16; 139(2): 299-311.
  • Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W.
  • View Abstract on PubMed
  • Inhibition of Wnt signaling by Dishevelled PDZ peptides.
  • Nat Chem Biol. 2009 Apr; 5(4): 217-9.
  • Zhang Y, Appleton BA, Wiesmann C, Lau T, Costa M, Hannoush RN, Sidhu SS.
  • View Abstract on PubMed
  • Liposomal packaging generates Wnt protein with in vivo biological activity.
  • PLoS One 2008 Aug 13; 3(8): e2930.
  • Morrell NT, Leucht P, Zhao L, Kim JB, ten Berge D, Ponnusamy K, Carre AL, Dudek H, Zachlederova M, McElhaney M, Brunton S, Gunzner J, Callow M, Polakis P, Costa M, Zhang XM, Helms JA, Nusse R.
  • View Abstract on PubMed
  • Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors.
  • Cancer Cell 2005 Apr ;7(4): 325-36.
  • Lackner MR, Kindt RM, Carroll PM, Brown K, Cancilla MR, Chen C, de Silva H, Franke Y, Guan B, Heuer T, Hung T, Keegan K, Lee JM, Manne V, O'Brien C, Parry D, Perez-Villar JJ, Reddy RK, Xiao H, Zhan H, Cockett M, Plowman G, Fitzgerald K, Costa M, Ross-Macdonald P.
  • View Abstract on PubMed
  • Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family.
  • Genes Dev 2001 Mar 15; 15(6): 672-86.
  • Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, Buchman AR, Ferguson KC, Heller J, Platt DM, Pasquinelli AA, Liu LX, Doberstein SK, Ruvkun G.
  • View Abstract on PubMed
  • A putative catenin-cadherin system mediates morphogenesis of the Caenorhabditis elegans embryo.
  • J Cell Biol 1998 Apr 6; 141(1): 297-308.
  • Costa M, Raich W, Agbunag C, Leung B, Hardin J, Priess JR.
  • View Abstract on PubMed
  • Hyperactivation of the folded gastrulation pathway induces specific cell shape changes.
  • Development 1998 Feb; 125(4): 589-97.
  • Morize P, Christiansen AE, Costa M, Parks S, Wieschaus E.
  • View Abstract on PubMed
  • The dance of the Hox genes: patterning the anteroposterior body axis of Caenorhabditis elegans.
  • Cold Spring Harb Symp Quant Biol 1997; 62: 293-305.
  • Kenyon CJ, Austin J, Costa M, Cowing DW, Harris JM, Honigberg L, Hunter CP, Maloof JN, Muller-Immerglück MM, Salser SJ, Waring DA, Wang BB, Wrischnik LA.
  • View Abstract on PubMed
  • A putative cell signal encoded by the folded gastrulation gene coordinates cell shape changes during Drosophila gastrulation.
  • Cell 1994 Mar 25; 76(6): 1075-89.
  • Costa M, Wilson ET, Wieschaus E.
  • View Abstract on PubMed
  • Gastrulation in Drosophila: cellular mechanisms of morphogenetic movements. In: Bate M, Martinez-Arias A, editors.
  • The development of Drosophila melanogaster Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press; 1993. p. 425-66.
  • Costa M, Sweeton D, Wieschaus E.
  • (1991). Genes controlling cell shape changes during gastrulation in Drosophila melanogaster In: Gerhart J, editor.
  • Cell-cell interactions in early development. New York: Wiley-Liss; 1991.
  • Wieschaus E, Parks S, Costa M, Sweeton D.
  • Convergence and extension during germ band elongation in Drosophila embryos. In: Keller R, Clark W Jr, Griffini F, editors. Gastrulation: movements, patterns, and molecules.
  • New York: Plenum Press; 1991. p. 213-23.
  • Wieschaus E, Sweeton D, Costa M.
  • Gastrulation in Drosophila: the formation of the ventral furrow and posterior midgut invaginations.
  • Development 1991 Jul; 112(3): 775-89.
  • Sweeton D, Parks S, Costa M, Wieschaus E.
  • View Abstract on PubMed
  • Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox.
  • Cell 1988 Dec 2; 55(5): 747-56.
  • Costa M, Weir M, Coulson A, Sulston J, Kenyon C.
  • View Abstract on PubMed
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Awards & Honors
  • Damon Runyon-Walter Winchell Foundation Postdoctoral Fellowship--1994-1997
  • Card Family Fund Dissertation Travel Research Award--1992

Mike Costa, 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.