Plenary 1– Global Trends in Biotech Industry (B)
Date: 22 July (Wednesday) 10:30 – 12:10 (GMT+8)
Venue: 701EF, 7F, TaiNEX2 / Online event platform
Hans Clevers (1957) 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. From 2012-2015 he was President of the Royal Netherlands Academy of Arts and Sciences (KNAW). From 2015 - June 2019 he was Director Research of the Princess Maxima Center for pediatric oncology. He continues to run his lab in the Hubrecht Institute.
Throughout his career, he has worked on the role of Wnt signalling in stem cells and cancer. His discoveries include TCF as the nuclear Wnt effector, the role of Wnt in adult stem cell biology and of Wnt pathway mutations in colon cancer, Lgr5 as a marker of multiple novel types of adult stem cells and as receptor for the Wnt-amplifying R-spondins, and –finally- a method to grow ever-expanding mini-organs (‘organoids’) from Lgr5 stem cells derived from a range of healthy or diseased human tissues. This has led to over 600 publications and >70,000 citations.
Hans Clevers is member of the Royal Netherlands Academy of Arts and Sciences (2000), of the American Academy of Arts and Sciences (2012) and the National Academy of Sciences of the USA (2014), the Academie des Sciences (2016) and the Orden pour le Merite der Wisschschaften und Kuenste (2017).
He is the recipient of multiple awards, including the Dutch Spinoza Award in 2001, the Swiss Louis Jeantet Prize in 2004, the German Meyenburg Cancer Research Award in 2008, the German Ernst Jung-Preis für Medizin in 2011, the French Association pour la Recherche sur le Cancer (ARC) Léopold Griffuel Prize, the Heineken Prize (2012), the Breakthrough Prize in Life Sciences (2013), the 2015 ISSCR McEwen Award for Innovation and the Academy Professor Prize (2015), and the Körber European Science Prize (2016). He is Chevalier de la Legion d’Honneur since 2005, Knight in the Order of the Netherlands Lion since 2012 and German prize.
Speech title & Synopsis
The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. We originally defined Lgr5 as a Wnt target gene, transcribed in colon cancer cells. Two knock-in alleles revealed exclusive expression of Lgr5 in cycling, columnar cells at the crypt base. Using lineage tracing experiments in adult mice, we found that these Lgr5+ve crypt base columnar cells (CBC) generated all epithelial lineages throughout life, implying that they represent the stem cell of the small intestine and colon. Lgr5 was subsequently found to represent an exquisitely specific, yet 'generic' marker for active epithelial stem cells in essentially all organs.
Single sorted Lgr5+ve stem cells can initiate ever-expanding crypt-villus organoids, or so called 'mini-guts' in 3D culture. The technology is based on the observation that Lgr5 is the receptor for a potent stem cell growth factor, R-spondin. Similar 3D cultures systems have been developed for the Lgr5+ve stem cells of human stomach, liver, pancreas, breast etc. Using CRISPR/Cas9 technology, genes can be efficiently modified in organoids of various origins. Organoid technology opens a range of avenues for the study of development, physiology and disease, for drug development and for personalized medicine. In the long run, cultured mini-organs may replace transplant organs from donors and hold promise in gene therapy.