Hans Clevers, MD PhD

Keynote lecture: Prof. dr. Hans Clevers, MD PhD

 
"Lgr5 Stem Cells in self-renewal and cancer"
The intestinal epithelium is the most rapidly self-renewing tissue in mammals. Lgr5 is expresed in small cycling cells at the crypt base. Using an inducible Cre knock-in allele, lineage tracing experiments were performed. The Lgr5+ve cells generated all epithelial lineages over a 14 month period, thus representing the stem cell of the small intestine and colon. Similar obserations were made in hair follicles and stomach epithelium. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.
Long-term culture conditions were established under which single Lgr5+ve stem cells generate ever-expanding crypt/villus organoids containing all differentiated cell types. The same technology has now been developed for the Lgr5+ve stomach stem cells.
Intestinal cancer is initiated by APC. The cell-of-origin has remained elusive. Deletion of APC in Lgr5+ve stem cells leads to their transformation within days. Transformed stem cells remain located at crypt bottoms, while fueling a growing microadenoma in stomach, small intestine and colon. These microadenomas develop into macroscopic adenomas within 4-6 weeks. Moreover, a stem cell/progenitor cell hierarchy is maintained in early stem cell-derived adenomas, lending support to the "cancer stem cell"-concept.

About Hans Clevers
Hans Clevers obtained his MD degree in 1984 and his PhD degree in 1985 from the University of 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 of Utrecht and, since 2002, Professor in Molecular Genetics. Since 2002, he is Director of the Hubrecht Institute in Utrecht .
Hans Clevers has been a member of the Royal Netherlands Academy of Arts and Sciences since 2000 and 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, and the Dutch Josephine Nefkens Prize for Cancer Research and the German Meyenburg Cancer Research Award in 2008. He obtained an ERC Advanced Investigator grant in 2008. He is Chevalier de la Legion d'Honneur since 2005.