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Scientist Profile

Frederic de Sauvage

Vice President, Molecular Biology
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"Collaborations, internal and external, are key to success at Genentech."

I came to Genentech in 1990 thinking I would be here only for a few years. I loved the work and the culture so much that I've been here ever since.

Over the years I have had many collaborations across the company. Recently, my lab's interest was mostly focused on the characterization of the hedgehog signaling pathway and the development of pathway antagonists for the treatment of various cancer. This project has evolved into a multidisciplinary project that involves many departments across the organization, which has given me the opportunity to interact with fantastic people.

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My Focus

We are studying and targeting a number of important signaling pathways such as Ras, Hedgehog and Notch. Development pathways such as Wnt, Hedgehog and Notch play critical roles during embryogenesis where they modulate proliferation or differentiation of numerous cell types. It is however becoming increasingly clear that these pathways are involved in tumorigenesis when reactivated in adult tissues through mutations or overexpression of pathway components. We are also involved in a number of earlier stage initiatives such as the investigation of therapeutic use of RNAi, using genetic mouse models of cancer to better predict drug efficacy as well as cancer and functional genome projects to identify novel drug targets in various therapeutic areas.

 
Postdoctoral Mentor

The Hedgehog (Hh) pathway is a signaling cascade that directs patterning in most animals and is crucial for proper development. At the molecular level, Hh ligands drive cell proliferation in some cell types while causing others to undergo differentiation. Hh signaling is most active during embryogenesis and aberrant reactivation of the pathway in adult tissue can lead to the development of cancer. Mutations in the Hh receptor components, Patched (PTCH1) or Smoothened (SMOH), result in constitutive pathway activation and have been identified in basal cell carcinoma and medulloblastoma. It has also been observed that Hh ligand production is upregulated in other cancer types such as pancreatic adenocarcinomas. The mechanisms by which the Hh signal is transmitted inside the cell, leading ultimately to the activation of the GLI family of transcription factors also remains poorly understood. The lab is interested in (i) understanding the contribution of Hh signaling in cancer by using genetic mouse models of cancer, (ii) uncovering signaling mechanisms by which the Hh signal is transduced into a cell and potentially novel therapeutic targets for the treatment of cancer and finally (iii) develop antagonists of the Hh pathway that can be used in the clinic to treat various types of tumors where the Hh pathway is activated.

 
Publications & Recognition
  • Structural ties between cholesterol transport and morphogen signaling.
  • Cell 2009 Sep 18; 138(6): 1055-6.
  • Bazan JF, de Sauvage FJ.
  • View Abstract on PubMed
  • Smoothened mutation confers resistance to a hedgehog pathway inhibitor in medulloblastoma.
  • Science 2009 Sep 2.
  • Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, Pujara K, Stinson J, Callahan CA, Tang T, Bazan JF, Kan Z, Seshagiri S, Hann CL, Gould SE, Low JA, Rudin CM, de Sauvage FJ.
  • View Abstract on PubMed
  • Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.
  • N Engl J Med 2009 Sep 17; 361(12): 1164-72.
  • Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JF, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA.
  • View Abstract on PubMed
 
View All Publications & Recognition
 
  • Catholic University of Louvain
  • Belgium, Department of Science, Ph.D.
  • 1990
  • Catholic University of Louvain
  • B.S. Belgium, Department of Chemistry
  • 1985
Publications & Recognition
  • Structural ties between cholesterol transport and morphogen signaling.
  • Cell 2009 Sep 18; 138(6): 1055-6.
  • Bazan JF, de Sauvage FJ.
  • View Abstract on PubMed
  • Smoothened mutation confers resistance to a hedgehog pathway inhibitor in medulloblastoma.
  • Science 2009 Sep 2.
  • Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, Pujara K, Stinson J, Callahan CA, Tang T, Bazan JF, Kan Z, Seshagiri S, Hann CL, Gould SE, Low JA, Rudin CM, de Sauvage FJ.
  • View Abstract on PubMed
  • Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.
  • N Engl J Med 2009 Sep 17; 361(12): 1164-72.
  • Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, Weiss GJ, Borad MJ, Hann CL, Brahmer JF, Mackey HM, Lum BL, Darbonne WC, Marsters JC Jr, de Sauvage FJ, Low JA.
  • View Abstract on PubMed
  • Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449.
  • N Engl J Med 2009 Sep 17; 361(12): 1173-8.
  • Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, Holcomb T, Stinson J, Gould SE, Coleman B, LoRusso PM, Von Hoff DD, de Sauvage FJ, Low JA.
  • View Abstract on PubMed
  • Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis.
  • Proc Natl Acad Sci USA 2009 Mar 17; 106(11): 4254-9.
  • Tian H, Callahan CA, DuPree KJ, Darbonne WC, Ahn CP, Scales SJ, de Sauvage FJ.
  • View Abstract on PubMed
  • Kinome siRNA screen identifies regulators of ciliogenesis and hedgehog signal transduction.
  • Sci Signal 2008 Sep 30; 1(39): ra7.
  • Evangelista M, Lim TY, Lee J, Parker L, Ashique A, Peterson AS, Ye W, Davis DP, de Sauvage FJ.
  • View Abstract on PubMed
  • A paracrine requirement for hedgehog signalling in cancer.
  • Nature 2008 Sep 18; 455(7211): 406-10.
  • Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, Nannini-Pepe M, Kotkow K, Marsters JF, Rubin LL, de Sauvage FJ.
  • View Abstract on PubMed
  • Targeting the Hedgehog pathway in cancer.
  • Nat Rev Drug Discov 2006 Dec; 5(12): 1026-33.
  • Rubin LL, de Sauvage FJ.
  • View Abstract on PubMed
  • Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells.
  • Nat Immunol 2006 Sep; 7(9): 929-36.
  • Batten M, Li J, Yi S, Kljavin NM, Danilenko DM, Lucas S, Lee J, de Sauvage FJ, Ghilardi N.
  • View Abstract on PubMed
  • Loss of the serine/threonine kinase fused results in postnatal growth defects and lethality due to progressive hydrocephalus.
  • Mol Cell Biol 2005 Aug; 25(16): 7054-68.
  • Merchant M, Evangelista M, Luoh SM, Frantz GD, Chalasani S, Carano RA, van Hoy M, Ramirez J, Ogasawara AK, McFarland LM, Filvaroff EH, French DM, de Sauvage FJ.
  • View Abstract on PubMed
  • Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice.
  • J Immunol 2004 Mar 1; 172(5): 2827-33.
  • Ghilardi N, Kljavin N, Chen Q, Lucas S, Gurney AL, De Sauvage FJ.
  • View Abstract on PubMed
  • IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms.
  • Proc Natl Acad Sci U S A 2003 Dec 9; 100(25): 15047-52.
  • Lucas S, Ghilardi N, Li J, de Sauvage FJ.
  • View Abstract on PubMed
  • Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17.
  • J Biol Chem 2003 Jan 17; 278(3): 1910-4.
  • Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL.
  • View Abstract on PubMed
  • Development of Th1-type immune responses requires the type I cytokine receptor TCCR.
  • Nature 2000 Oct 19; 407(6806): 916-20.
  • Chen Q, Ghilardi N, Wang H, Baker T, Xie MH, Gurney A, Grewal IS, de Sauvage FJ.
  • View Abstract on PubMed
  • Activating Smoothened mutations in sporadic basal-cell carcinoma.
  • Nature 1998 Jan 1; 391(6662): 90-2.
  • Jingwu Xie, Maximilien Murone, Shiuh-Ming Luoh, Anne Ryan, Chaohui Zhang, Quimin Gu, Jeannette M. Bonifas, Ching-Wan Lam, Mary Hynes, Audrey Goddard, Xie Xie J, Murone M, Luoh SM, Ryan A, Gu Q, Zhang C, Bonifas JM, Lam CW, Hynes M, Goddard A, Rosenthal A, Epstein EH Jr, de Sauvage FJ.
  • View Abstract on PubMed
  • The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.
  • Nature 1996 Nov 14; 384(6605): 129-34.
  • Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F, Rosenthal A.
  • View Abstract on PubMed
  • Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets.
  • Blood 1996 Mar 15; 87(6): 2154-61.
  • Fielder PJ, Gurney AL, Stefanich E, Marian M, Moore MW, Carver-Moore K, de Sauvage FJ.
  • View Abstract on PubMed
  • Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin.
  • J Exp Med 1996 Feb 1; 183(2): 651-6.
  • de Sauvage FJ, Carver-Moore K, Luoh SM, Ryan A, Dowd M, Eaton DL, Moore MW.
  • View Abstract on PubMed
  • Thrombocytopenia in c-mpl-deficient mice.
  • CScience 1994 Sep 2; 265(5177): 1445-7.
  • Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW.
  • View Abstract on PubMed
  • Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand.
  • Nature 1994 Jun 16; 369(6481): 533-8.
  • de Sauvage FJ, Hass PE, Spencer SD, Malloy BE, Gurney AL, Spencer SA, Darbonne WC, Henzel WJ, Wong SC, Kuang WJ, Oles K, Hultgren B, Solber, L, Goeddel D, Eaton D.
  • View Abstract on PubMed
  • A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein.
  • Science 1989 Aug 11; 245(4918): 651-3.
  • de Sauvage F, Octave JN.
  • View Abstract on PubMed
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Frederic de Sauvage, 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.