Hans Clevers

Clevers and his team thus showed that “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 Wnt pathway had been studied by many other people that way we could use assays of those people. We then realized that in mammals Wnt signaling...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 Wnt signaling and stem cells in adults. And in that same year we found in a collaboration with Bert Vogelstein 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.”

After this Clevers's team “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 finally identified the stem cells in the gut. And we now can purify them in large numbers and study their characteristics.”

Asked in a 2008 interview what had been the highlights of his research up to that point, Clevers said “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. 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 Wnt signaling pathway, and this [was] 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.”

In 1991 Clevers became a professor of immunology at the University Medical Center in Utrecht. Since 2002 he has been a professor of molecular genetics at UMC Utrecht and Utrecht University. Also in 2002 he became director of the Hubrecht Institute for Developmental Biology and Stem-Cell Research at the Royal Netherlands Academy of Arts and Sciences. Clevers discovered similarities between the normal renewal of intestinal tissue and the onset of colon cancer. In 2008 and 2015 he received ERC Advanced Investigator Grants. In 2013 he was awarded the $3 million Breakthrough Prize in Life Sciences for his work. In March 2012, Clevers, who since 2000 had been a member of the Royal Netherlands Academy of Arts and Sciences, was elected its president, succeeding Robbert Dijkgraaf. In connection with his election to this position, he resigned as director from the Hubrecht Institute but kept his research lab there. From 2012-2015 he was President of the Royal Netherlands Academy of Arts and Sciences (KNAW). From 2015-2019 he was director Research of the Princess Maxima Center for paediatric oncology, located on the Utrecht Science Park close to the Hubrecht where he maintains his lab. Presently, Clevers leads two research group, one at the Hubrecht Institute as well as at the Princess Maxima Center.

Hans Clevers began studying biology at the University of Utrecht in 1975, then began studying medicine as well. He spent part of his seven years of biological study in Nairobi, Kenya, and also, in his words, “did some rotations” at the National Institutes of Health in Bethesda. He received an M.Sc. in Biology in 1982, an M.D. in 1984 and a Ph.D. in 1985. For his Ph.D. he studied under Rudy Ballieux. From 1986 to 1989 he did postdoctoral work under the direction of Cox Terhorst at the Dana-Farber Cancer Institute at Harvard University. It was there that Clevers cloned the T-cell gene CD3 epsilon. After his stay at Harvard, he returned to the Netherlands to start his own research group at the department of Clinical immunology of the UMC Utrecht. Describing his path to his career as a medical researcher, Clevers said the following: “There was a bit of an awkward route. I actually studied biology first, and then took up medical school at about the same time....Did two separate studies, graduated from both, was going to be a pediatrician, then decided to spend a year in science, liked it so much more that I realized I didn’t – I shouldn’t become a real doctor. I was not good with – I liked patients, but I was a little bit impatient with them. I then decided to go for a post-doc at Boston to Dana Farber, where I really learned the trade.”