Chris Siebel

Senior Scientist, Molecular Biology

POSTDOC MENTOR

• 18
  years at Genentech
• 5
  publications (2010-12)

Our research is aimed at understanding the role of Notch signaling in cancer. The Notch signal transduction pathway, initially discovered nearly 100 years ago as one of the first haploinsufficient genetic mutations in Drosophila, represents a highly conserved mechanism through which cells communicate with each other. This communication has been best studied as a mediator of binary cell fate decisions, but it also affects a wide range of cellular processes such as proliferation, stem cell renewal and apoptosis.

Consistent with this central role in controlling cellular metabolism, aberrant Notch signaling has been implicated in numerous cancers. Activating mutations in the Notch1 receptor have been shown to cause T cell acute lymphoblastic leukemia (T-ALL), and increased Notch activity or expression correlates with the development of a myriad of solid tumor types. Moreover, Notch signaling controls the extent of angiogenic sprouting, and targeting the pathway may inhibit the proper development of tumor vasculature.

A few primary questions anchor our research efforts: What human cancers are driven by Notch signaling, and how does the pathway affect distinct aspects of oncogenesis, including proliferation, apoptosis and cell movement? What is the mechanism of Notch receptor activation, and can we develop therapeutics that control it? How do mammalian cells regulate Notch signaling, either with novel cell-surface proteins or intracellular modulators, and what are the molecular mechanisms through which Notch "crosstalks" with other signaling pathways? We are addressing these questions using a variety of techniques, ranging from biochemical structure-function studies to genetic screens and in vivo models, with the ultimate goals of illuminating fundamental aspects of mammalian Notch biology and discovering new ways to treat cancer.

• My Focus

• Publications

  • Real-time quantification of antibody-siRNA conjugate in serum by antigen-capture RT-PCR

    Analytical Biochemistry, 2012, ISSN: 0003-2697

    Tan, Martha; Vernes, Jean-Michel; Chan, Joyce; Cuellar, Trinna L; Asundi, Aarati; Nelson, Christopher; Yip, Victor; Shen, Ben; Vandlen, Richard; Siebel, Christian; Gloria Meng, Y

     View on PubMed

  • Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells

    Development, 2012, ISSN: 0950-1991

    VanDussen, Kelli L.; Carulli, Alexis J.; Keeley, Theresa M.; Dempsey, Peter J.; Samuelson, Linda C.; Patel, Sanjeevkumar R.; Maillard, Ivan; Puthoff, Brent J.; Magness, Scott T.; Tran, Ivy T.; Kolterud, Åsa; Grosse, Ann S.; Gumucio, Deborah L.; Ernst, Stephen A.; Siebel, Christian; Tsai, Yu-Hwai

     View on PubMed

  • The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development.

    Blood, {Blood}, 23 Jun 2011 (epub: 23 6 2011), ISSN: 1528-0020.

    Niessen, Kyle; Zhang, Gu; Ridgway, John Brady; Chen, Hao; Kolumam, Ganesh; Siebel, Christian W; Yan, Minhong

     View on PubMed

  • Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia.

    Nature Immunology, 2010, ISSN: 1529-2908

    Hodson, D.; Janas, M.; Galloway, A.; Bell, S.; Andrews, S.; Li, C.; Pannell, R.; Siebel, C.; Mac Donald, H.R.; De Keersmaecker, K.; Ferrando, A.; Grutz, G.; Turner, M.

  • Therapeutic antibody targeting of individual Notch receptors.

    Nature, 2010, ISSN: 1476-4687

    Wu, Y.; Cain-Hom, C.; Choy, L.; Hagenbeek, T.J.; de Leon, G.P.; Chen, Y.; Finkle, D.; Venook, R.; Wu, X.; Ridgway, J.; Schahin-Reed, D.; Dow, G.J.; Shelton, A.; Stawicki, S.; Watts, R.J.; Zhang, J.; Choy, R.; Howard, P.; Kadyk, L.; Yan, M.; Zha, J.; Callahan, C.A.; Hymowitz, S.G.; Siebel, C.W.

• Education
  • University of California, San Francisco, Postdoctoral Fellow – 1993-1998
  • University of California Berkeley, Postdoctoral Fellow – 1992-1993
  • Massachusetts Institute of Technology, Ph.D. – 1992
  • Pomona College, B.A. – 1985