Recorded: 29 May 2008
Yes, I think the highlights in my research—there would probably be three. There was a first one, when I just started my lab, within the first few months we cloned the gene that they call TCF1, t-cell factor 1, I used to be a t-cell embryologist when we first started out. And that paper was published in EMBO in ’91, first author. So in that paper we described cloning of this vector, which at that time maybe on the world scale was not great but for my own lab to clone this gene was my first thing I ever did alone. This gene then in ’96 we found to be the crucial missing component of what’s called the wind signaling pathway, and this generally seen as a major breakthrough we had. There were papers in ’96 and ’97 in Cell, and we had two papers in Science in the same two years. And that really—so what we showed there is that this TCF transcription factor, there is a small family of them, they occur in every animal on the planet, they are the end point of the signal transcription cascade, and they control virtually every decision in a developing animal. When we realized this we started changing our model systems, we used to work on lymphocytes, and we changed it, first to frogs and flies, drosophila, where the wind pathway had been studied by many other people that way we could use essays of those people. We then realized that in mammals wind signaling was only important--was not only important in embryos but also crucial in adults, which is novel. And we switched to the gut, we found that one of our knockouts, the TCF4 knockout, one of the four members of that family had no stem cells in the gut. And this is the first link in the literature, this was also a ’97 paper in Nature Genetics, between wind signaling and stem cells in adults. And in that same year we found that colon cancer comes about by the disregulation of TCF4, and those two phenomena are really linked. So stem cells need TCF4, cancers disregulate TCF4 by mutating a gene upstream in that pathway called APC. And then I think, well then my lab continued to work on the intestine and on the physiology of the intestine, which was essentially an unstudied field, much to my surprise. May I emphasize, there are thousands of very competent embryologists, and they work on tiny details, and they fight over the smallest details, are extremely competent. In this intestinal field there are thousands of gastroentromologists that study cancer or colitis or Crohn’s Disease, but there are very few, if any, labs studying normal tissue, which is amazing because that is a tissue that we use every five days. It’s the most rapidly proliferating tissue in a normal body. So my lab actually build up a lot of mouse models and we learn a lot about how that’s being done, and then finally last year we, we sort of talk about this on the Symposium, last year we finally identified the stem cells in the gut. And we now can purify them in large numbers and study their characteristics.
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. 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.