HANS CLEVERS NL
Hubrecht Institute, Utrecht, Netherlands
Monday, 23 September, 09:00-09:45, Auditorium
Lgr5 Stem Cells in self-renewal and cancer
The intestinal epithelium is the most rapidly self-renewing mammalian tissue. Lgr5 is a gene transcribed in cycling, crypt base columnar cells at the crypt base. Using lineage tracing experiments the Lgr5+ve cells were identified as the stem cells of the intestinal epithelium. Furthermore, Lgr5+ve stem cells can initiate ever-expanding organoids in vitro. The Lgr5+ve stem cell hierarchy of differentiation is maintained in these organoids. Thus, intestinal crypt-villus units can be built from a single stem cell in the absence of a non-epithelial cellular niche. Although, Lgr5 stem cells persist life-long, crypts drift toward clonality quickly. The cellular dynamics are consistent with a model in which the stem cells divide symmetrically, and stochastically adopt stem or transient amplifying cell fates after cell division. Lgr5 stem cells are interspersed between differentiated Paneth cells, which produce all essential signals for stem-cell maintenance. Co-culturing of sorted stem cells with Paneth cells dramatically improves organoid formation. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells. Intestinal cancer is initiated by Wnt pathway-activating mutations in genes such as APC. Deletion of APC in stem cells, but not in other crypt cells results in neoplasia, identifying the stem cell as the cell-of-origin of adenomas. Moreover, a stem cell/progenitor cell hierarchy is maintained in stem cell-derived adenomas, lending support to the “cancer stem cell”-concept.
Hans Clevers obtained his MD degree in 1984 and his PhD degree in 1985 from the University Utrecht, the Netherlands. His postdoctoral work (1986-1989) was done with Cox Terhorst at the Dana-Farber Cancer Institute of the Harvard University, Boston, USA.
From 1991-2002 Hans Clevers was Professor in Immunology at the University Utrecht and, since 2002, Professor in Molecular Genetics. From 2002-2012 he was director of the Hubrecht Institute in Utrecht . Since 2012 he is President of the Royal Netherlands Academy of Arts and Sciences (KNAW).
Hans Clevers has been a member of the Royal Netherlands Academy of Arts and Sciences since 2000 and a member of the American Academy of Arts and Sciences since 2012. He is the recipient of several awards, including the Dutch Spinoza Award in 2001, the Swiss Louis Jeantet Prize in 2004, the Memorial Sloan-Kettering Katharine Berkan Judd Award in 2005, the Israeli Rabbi Shai Shacknai Memorial Prize in 2006, the Dutch Josephine Nefkens Prize for Cancer Research and the German Meyenburg Cancer Research Award in 2008, the Dutch Cancer Society Award in 2009, the United European Gastroenterology Federation (UEGF) Research Prize in 2010, the German Ernst Jung-Preis für Medizin in 2011 and the French Association pour la Recherche sur le Cancer (ARC) Léopold Griffuel Prize and the Heineken Prize in 2012. He obtained an ERC Advanced Investigator grant in 2008. He is Chevalier de la Legion d'Honneur since 2005 and Knight in the Order of the Netherlands Lion since 2012.