/ Scientists / Our Scientists Frederic de Sauvage - Vice President and Staff Scientist, Molecular Oncology

Frederic de Sauvage

Vice President and Staff Scientist, Molecular Oncology

Postdoc mentor iconPostdoc Mentor
Staff Scientist
"Collaborations, internal and external, are key to success at Genentech."
  • 24
    years at Genentech
  • 55
    publications (2009-14)

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.

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 tumors such as 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) understand the mechanism of resistance to hedgehog pathway inhibitors.

More recently my lab has become interested in the role of intestinal stem cells in homeostasis and in tumor development. While developing agents to target stem cells in the gut we have uncovered mechanism(s) of compensations that allows the GI track to tolerate depletion of the stem cell compartment during homeostasis but not under various challenge situations. However this mechanism probably also reflects a great deal of plasticity in tumors as well and we are studying the signaling mechanisms that underlie this phenomenon.

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