At the interface between stem cells and cancer
The Royal Netherlands Academy of Arts and Sciences has awarded the 2012 Dr A.H. Heineken Prize for Medicine (USD 150,000) to Hans Clevers (director of the Hubrecht Institute for Developmental Biology and Stem Cell Research, one of the Academy’s research Institutes, and professor at Utrecht University, the Netherlands). He is receiving the prize for his unique understanding of how tissue growth is regulated, both in normal development and in cancer.
Hans Clevers commenced his career in science by studying cells in the human immune system and signalling proteins that influence the development of immune cells. His findings quickly turned out to have much wider implications, however.
It became clear that the cellular chain reactions he had unravelled together constitute a crucial mechanism determining the direction of cell division and growth, not only in human beings, but also in other mammals, amphibians, worms and even insects.
Will the cells that make up a tiny embryo gradually grow into an entire stomach or intestine? Or will they furnish a daily supply of fresh intestinal epithelium cells in the adult? Or will the same regulatory mechanism be disrupted, causing the stem cell to suddenly change into one that develops into intestinal cancer?
Clevers’ findings and his visionary in-depth investment in new research methods and animal models helped found a new and flourishing field of medical research. Its quest is to identify stem cells, which have the ability to grow into new tissues and organs, and work to harness that ability to replace damaged tissue or even organs. Clevers’ laboratory has already succeeded in isolating stem cells and causing them to grow into miniscule stomachs.
Equally important is how his work is helping us discover why healthy stem cells sometimes turn into intestinal cancer cells, which genetic factors increase the chance of that happening, and what we may be able to accomplish with medication in future.
At present, Clevers’ discoveries are most tangible in the world of science. He has published hundreds of articles in leading journals such as Science, Nature and Cell, sources of tens of thousands of citations by other researchers around the world. Each one of his discoveries, however, also has the potential to bring about monumental changes in the medical world.
Hans Clevers was born in 1957. He studied medicine and biology at Utrecht University and obtained his PhD there in 1985, studying under clinical immunologist Professor R.E. Ballieux. He then spent four years at the Dana Farber Cancer Institute at Harvard Medical School in Boston, USA.
Clevers returned to Utrecht in 1991 and was appointed Chairman of the Department of Immunology. When the focus of his worked shifted, he was appointed Professor of Molecular Genetics and Director of the Hubrecht Institute, both in 2002. In these positions, he has become one of the leading figures in Dutch science.
Clevers' international reputation has brought him numerous grants and awards, for example the Dutch Spinoza Award, the Swiss Louis Jeantet Prize, the American Katharine Berkan Judd Award, the Israeli Rabbi Shai Shacknai Memorial Prize, the German Ernst Jung Prize for Medicine, and, very recently, the French Léopold Griffuel Prize for cancer research. Last year the Netherlands Organisation for Scientific Research (NWO) awarded him a grant of EUR 2 million to support his work on generating intestinal tissue from stem cells.
Professor Clevers is a member of the Royal Netherlands Academy of Arts and Sciences and the American Association for Cancer Research. In 2005 he was made a Chevalier in the Ordre national de la Légion d'honneur, one of the highest French distinctions.
- Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H. Science. 1997 Mar 21;275(5307):1784-7.
- The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, van der Horn K, Batlle E, Coudreuse D, Haramis AP, Tjon-Pon-Fong M, Moerer P, van den Born M, Soete G, Pals S, Eilers M, Medema R, Clevers H. Cell. 2002 Oct 18;111(2):241-50.
- Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Nature. 2009 May 14;459(7244):262-5.
- Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, Kroon-Veenboer C, Barker N, Klein AM, van Rheenen J, Simons BD, Clevers H. Cell. 2010 Oct 1;143(1):134-44
- Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering M, Stange DE, van Es J, Guardavaccaro D, Schasfoort RB, Mohri Y, Nishimori K, Mohammed S, Heck AJ, Clevers H. Nature. 2011 Jul 4. doi: 10.1038/nature10337.
The Dr A.H. Heineken Prize for Medicine was established in 1989. Previous laureates include Richard Peto, Paul Lauterbur (Nobel Prize in Medicine), David de Wied , Eric Kandel (Nobel Prize in Medicine), Elizabeth Blackburn (Nobel Prize in Medicine) and Mary-Claire King . The jury was chaired by Christine Mummery.
The Heineken Prizes will be presented on Thursday 27 September 2012 during an extraordinary meeting of the Royal Netherlands Academy of Arts and Sciences.