Hans Clevers

Hans Clevers
Clevers in 2013
Born	(1957-03-27) 27 March 1957 Eindhoven [1]
Nationality	Dutch
Fields	Molecular genetics
Institutions	Hubrecht Institute - Utrecht University - UMC Utrecht - The Princess Maxima Center for pediatric oncology
Education	University of Utrecht
Doctoral advisor	Cox Terhorst
Known for	Research on normal stem cells and their potential for regenerative therapy
Notable awards	Breakthrough Prize in Life Sciences

Johannes Carolus (Hans) Clevers (born 27 March 1957) is a professor in molecular genetics, a geneticist, physician, medical researcher who was the first to identify stem cells in the intestine and is one of the world's leading researchers on normal stem cells and their potential for regenerative therapy.^[2] Clevers obtained his M.D. in 1984 and his Ph.D. in 1985 at Utrecht University and was a professor in immunology there between 1991 and 2002. Since then, he is Professor in Molecular Genetics at the same university. He received the Spinoza Prize in 2001 and became director of the Hubrecht Institute in 2002. He was elected as the president of the Royal Netherlands Academy of Arts and Sciences (KNAW) to succeed Robbert Dijkgraaf from 2012-2015.^[3] Clevers has his own research group at the Hubrecht Institute and is director Research of the Princess Maxima Center for pediatric oncology since 1 June 2015. In 2013 he was awarded the $3 million Breakthrough Prize in Life Sciences for his work ^[4]

Early life and education

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 PhD he studied under Rudy Ballieux.^[5][6] 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 stint at Harvard, he returned to the Netherlands. 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.”^{[7][8][9][10][11]}

Career

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. Also in 2002 he became director of the Hubrecht Institute for Developmental Biology and Stem-Cell Research at the Royal Dutch Academy of Sciences. Clevers discovered similarities between the normal renewal of intestinal tissue and the onset of colon cancer. In 2007 he received a grant of two million euros from the Dutch Cancer Society (KWF) to study the function of stem cells in the normal intestines and in colon cancer, and in 2008 and 2015 he received ERC Advanced Investigator Grants. In March 2012, Clevers, who since 2000 had been a member of the Royal Netherlands Academy of Arts and Sciences, was elected its president, a position he assumed on 1 June of that year, 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.^{[7][8][9][10][12]} From 2012-2015 he was President of the Royal Netherlands Academy of Arts and Sciences (KNAW). Since 1 June 2015 he is director Research of the Princess Maxima Center for paediatric oncology, located on the Utrecht campus close to the Hubrecht where he maintains his lab.

Research

Highlights of research

To summarise his scientific highlights, Hans Clevers identified the crucial downstream component of the Wnt signaling cascade, TCF, and the mechanism by which Wnt signals activate specific TCF target genes. With these insights and in a collaboration with Bert Vogelstein, he proposed that in APC-deficient colon cancer, it is the inappropriate activation of the Wnt pathway that transforms cells.

He was the first to link Wnt signaling with adult stem cell biology, when he showed that TCF4 gene disruption leads to the abolition of crypt stem cell compartments of the gut. He went on to show that the Tcf4-driven target gene program in colorectal cancer cells is the malignant counterpart of a physiological crypt stem cell program.

He then described the Wnt target Lgr5 as a marker for adult stem cells including those of crypts. By the creation of several ingenious Lgr5-based transgenic mice, he established the intestinal crypt as one of the pre-eminent models to visualize and study adult stem cells in mammals. He described several counter-intuitive characteristics for crypt stem cells: Lgr5 stem cells are abundant, they cycle rapidly, they divide symmetrically, and utilize their Paneth cell-daughters as their niche.

He then identified the Wnt signal-enhancing Rspondins as ligands of Lgr5, and exploited the Rspondin/Lgr5 axis to develop a 3D organoid culture system for indefinite expansion of normal intestinal epithelium starting from a single adult Lgr5 stem cell. Similar results were then reported by him for multiple additional human and mouse tissues. This has opened ways to generate disease models directly from patients as well as avenues for regenerative medicine.

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.”

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.”^[7]

Other professional activities

Clevers holds a dozen patents and was involved in the establishment of the biotech firm Ubisys, which, with Ton Logtenberg as CEO, later merged with Introgene to become Crucell. Clevers also played a key role in the founding of Semaia Pharmaceuticals, which was later acquired by Hybrigenics SA.

He is on the editorial board Cell, Cell Stem Cell, Stem Cell Reports, EMBO Reports, Gastroenterology, amongst others.^{[7][8][9][10][12]}

He is a Scientific Advisory Board member for IMP in Vienna; the Institute for Research in Biomedicine in Barcelona and the Netherlands Cancer Institute (NKI) ^[9] He is also an honorary professor at Central South University in Changsha, Hunan, China.^[10]

He is member of the American Academy of Arts and Sciences (Boston), and foreign associate of the National Academy of Sciences (Washington) and the Academy des Sciences de l'Institut de France (Paris).

Honors and awards

Clevers has been recognized on a number of occasions for his research:

• 1999: Elected EMBO member
• 2000: Elected Royal Netherlands Academy of Arts and Sciences member^[13]
  • Catharijne-prize for medical science
• 2001: Award from the European Society for Clinical Investigation
  • Spinoza Prize (Netherlands)^[14]
• 2004: Louis-Jeantet Prize for Medicine (Switzerland)
  • Named Chevalier of the Légion d'honneur (France)
• 2005: Memorial Sloan-Kettering Katharine Berkan Judd Award (U.S.)
  • Science and Society Prize
• 2006: Rabbi Shai Shacknai Memorial Prize for Immunology and Cancer Research (Israel)
• 2008: Josephine Nefkens Prize for Cancer Research from Erasmus MC Rotterdam (Netherlands)
  • Meyenburg Cancer Research Award (Germany)
• 2009: Dutch Cancer Society Award
• 2010: United European Gastroenterology Federation (UEGF) Research Prize
• 2011: Ernst Jung Prize for Medicine from the Jung Foundation for Science and Research (Germany)
• 2012: Léopold Griffuel Prize from Association pour la Recherche sur le Cancer (France)
  • Kolff Prize
  • Knight of the Order of the Netherlands Lion (Netherlands)
  • William Beaumont Prize of the American Gastroenterology Association
  • Dr A.H. Heineken Prize for Medicine (Netherlands)^[8][9]
• 2013: Breakthrough Prize in Life Sciences
• 2014: Massachusetts General Hospital Award in Cancer Research
• 2014: TEFAF Oncology Chair 2014
• 2014: Fellow of the AACR Academy
• 2014: Struyvenberg European Society for Clinical Investigation (ESCI) medal
• 2015: ISSCR-McEwen Award for Innovation
• 2016: Royal Netherlands Academy of Arts and Sciences Professor Prize^[15]
• 2016: Kazemi Prize of Royan Research Institute (Iran)

Major publications

Clevers has more than 540 publications to his name and has been cited a total of more than 62,000 times. His h-index is 127. Some of his most important publications are:

• van de Wetering, M., Oosterwegel, M., Dooijes, D., and Clevers, H.C. Identification and cloning of TCF-1, a T cell-specific transcription factor containing a sequence-specific HMG box. EMBO J. 10:123-132 (1991)
• Verbeek, J.S., Ison, D., Hofhuis, F., Robanus-Maandag, E., te Riele, H., van de Wetering, M., Oosterwegel, M., Wilson, A., MacDonald, H.R. and Clevers, H.C. An HMG box containing T-cell factor required for thymocyte differentiation. Nature 374: 70-74 (1995)
• Schilham, M., Oosterwegel, M., Moerer, P., Jing Ya, de Boer, P., van de Wetering, M., Verbeek, S., S., Lamers, W., Kruisbeek, A., Cumano, A., and Clevers, H.Sox-4 gene is required for cardiac outflow tract formation and pro-B lymphocyte expansion. Nature 380: 711-714 (1996)
• Molenaar, M., Van de Wetering, M., Oosterwegel, M., Peterson-Maduro, J., Godsave, S., Korinek, V., Roose, J., Destrée, O. And Clevers, H. Xtcf-3 Transcription factor mediates beta-catenin-induced axis formation in xenopus embryos. Cell 86: 391-399 (1996)
• Korinek, V, Barker, N., Morin, P.J., van Wichen, D., de Weger, R., Kinzler, K.W., Vogelstein, B., and Clevers, H. Constitutive Transcriptional Activation by a beta-catenin-Tcf complex in APC-/- Colon Carcinoma. Science 275: 1784-1787 (1997)
• Morin, P.J., Sparks, A., Korinek, V., Barker, N., Clevers, H., Vogelstein, B., and Kinzler, K. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275: 1787-1790 (1997)
• van de Wetering, M., Cavallo, R., Dooijes, D., van Beest, M., van Es, J., Loureiro, J., Ypma, A., Hursh, D., Jones, T., Bejsovec, A., Peifer, M., Mortin, M., and Clevers, H. Armadillo co-activates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88, 789-799 (1997)
• Korinek, V., Barker, N., Moerer, P., van Donselaar, E., Huls, G., Peters, P.J. and Clevers, H. Depletion of epithelial stem cell compartments in the small intestine of mice lacking Tcf 4. Nat Genet 19: 379 383 (1998)
• Roose, J., Molenaar, M., Peterson, J., Hurenkamp, J., Brantjes, H., Moerer, P., van de Wetering, M., Destree, O., and Clevers, H. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395: 608-612 (1998)
• Roose, J., Huls, G., van Beest, M., Moerer, P., van der Horn, K., Goldschmeding, R., Logtenberg, T., and Clevers, H. Synergie between tumor suppressor APC and the beta-catenin/Tcf4 target gene Tcf1. Science 285: 1923-1926 (1999)
• Korswagen, R., Herman, M. and Clevers, H. Separate beta-catenins mediate Wnt signaling and cadherin adhesion in C. elegans. Nature 406: 527-532 (2000)
• Bienz, M., and Clevers, H. Linking colorectal cancer to Wnt signaling. Review Cell 103: 311-320 (2000)
• van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Horn, K., Batlle, E., Coudreuse, D., Haramis, A-P., Tjon-Pon-Fong, M., Moerer, P., van den Born, M., Soete, G., Pals, S., Eilers, M., Medema, R., Clevers, H. The beta catenin/TCF4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111: 241-250 (2002)
• Batlle, E., Henderson, J.T., Beghtel, H., van den Born, M., Sancho, E., Huls, G., Meeldijk, J., Robertson, J., van de Wetering, M., Pawson, T., Clevers, H. Beta- catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell 111: 251-263 (2002)
• Hurlstone, A.F., Haramis, A.P., Wienholds, E., Begthel, H., Korving, J., van Eeden, F., Cuppen, E., Zivkovic, D., Plasterk, R.H., Clevers, H. The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature 425: 633-637 (2003)
• Baas, A.F., Kuipers, J., van der Wel, N.N., Batlle, E., Koerten, H.K., Peters, P.J., Clevers, H.C. Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Cell 116: 457-466 (2004)
• Haramis, A.P., Begthel, H., van den Born, M., van Es, J., Jonkheer, S., Offerhaus, G.J., Clevers, H. De novo crypt formation and Juvenile Polyposis upon BMP inhibition. Science 303: 1684-1686 (2004)
• Radtke, F and Clevers, H., Self-renewal and cancer of the gut: Two sides of a coin. Review Science 307: 1904-1909 (2005)
• Reya, T., Clevers, H., Wnt signalling in stem cells and cancer. Review. Nature 434: 843-850 (2005)
• Van Es, J.H., Van Gijn, M.E., Riccio, O., van den Born, M., Vooijs, M., Begthel, H., Cozijnsen, M., Robine, S., Winton, D.J., Radtke, F., Clevers H. Notch pathway/γ-secretase inhibition turns proliferative cells in intestinal crypts and neoplasia into Goblet cells. Nature 435: 959-963 (2005)
• Batlle, E., Bacani, J., Begthel, H., Jonkheer, S., Gregorieff, A., van de Born, M., Malats, N., Sancho, E., Boon, E., Pawson, T., Gallinger, S., Pals, S., Clevers, H. EphB activity suppresses colorectal cancer progression Nature 435: 1126-1130 (2005)
• Clevers, H. Wnt/β-catenin signaling in development and disease, Review Cell 127: 469-480 (2006)
• Barker, N., Van Es, J.H., Kuipers, J., Kujala, P., Van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P.J., Clevers, H. Identification of stem cells in small intestine and colon by the marker gene LGR5. Nature 449: 1003-1007 (2007)
• Jaks, V., Barker, N, Kasper, M., van Es, J.H., Snippert, H.J., Clevers, H., Toftgård, R. Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet. 40: 1291-1299 (2008)
• Barker, N., Ridgway, R.A., van Es, J.H.,van de Wetering, M., Begthel, H., van den Born, M., Danenberg, E., Clarke, A.R., Sansom, O.J., Clevers, H. Crypt Stem Cells as the Cells-of-Origin of Intestinal Cancer. Nature 457: 608-611 (2009)
• van der Flier, L.G., van Gijn, M.E., Hatzis, P., Kujala, P., Haegebarth, A., Stange, D.E., Begthel, H., van den Born, M., Guryev, V., Oving, I., van Es, J.H., Barker, N., Peters, P.J., van de Wetering, M. and Clevers, H. Transcription Factor Achaete Scute-Like 2 Controls Intestinal Stem Cell Fate. Cell 136: 903-912 (2009)
• Sato, T., Vries, R., Snippert, H., van de Wetering, M., Barker, N., Stange, D., van Es, J., Abo, A., Kujala, P., Peters, P., and Clevers, H. Single lgr5 gut stem cells build crypt-villus structures in vitro without a stromal niche. Nature 459 :262-265 (2009)
• Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H.J., van Es, J.H., Sato, T., Stange, D.E., Begthel, H., van den Born, M., Danenberg, E., van den Brink, S., Korving, J., Abo, A., Peters, P.J., Wright, N., Poulsom, R., Clevers, H. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6: 25-36 (2010)
• Snippert, H.J., Haegebarth, A., Kasper, M., Jaks, V., van Es, J.H., Barker, N., van de Wetering, M., van den Born, M., Begthel, H., Vries, R.G., Stange, D.E., Toftgård, R., Clevers H. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 327: 1385-1389 (2010)
• Sato, T., van Es, J.H., Snippert, H.J., Stange, D.E., Vries, R.G., van den Born, M., Barker, N., Shroyer, N.F., van de Wetering, M., Clevers, H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469: 415-418 (2011)
• Snippert, J., van der Flier, L.G., Sato, T., van Es, J.H., van den Born, M., Kroon-Veenboer, C., Barker, N.,Klein, A.M., van Rheenen, J. Benjamin D. Simons, B.D. and Clevers, H. Intestinal Crypt Homeostasis results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells. Cell 143:134-44 (2010)
• de Lau, W., Barker, N., Low, T.Y., Koo, B.K., Li, V.S., Teunissen, H., Kujala, P., Haegebarth, A., Peters, P.J., van de Wetering, M., Stange, D.E., van Es, J., Guardavaccaro, D., Schasfoort, R.B., Mohri, Y., Nishimori, K., Mohammed,S., Heck, A.J., Clevers, H. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476: 293-297 (2011)
• Li, V.S., Ng, S.S., Boersema, P.J., Low, T.Y., Karthaus, W.R., Gerlach, J.P., Mohammed, S., Heck, A.J., Maurice, M.M., Mahmoudi, T. and Clevers H. Wnt signaling inhibits proteasomal β-catenin degradation within a compositionally intact Axin1 complex. Cell 149: 1245-1256 (2012)
• Koo, B-K., Spit, M. Jordens, I., Low, T.Y., Stange, D.E., van de Wetering, M., van Es, J.H., Mohammed, S., Heck, A.J.R., Maurice, M.M. and Hans Clevers. Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488: 665-669 (2012)
• Schepers, A.G., Snippert, H.J., Stange, D.E., van den Born, M., van Es, J.H., van de Wetering, M., Clevers, H. Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas. Science 337: 730-735 (2012)
• van Es, J.H., Sato, T., van de Wetering, M., Lyubimova, A., Yee Nee, A.N., Gregorieff, A., Sasaki, N., Zeinstra, L., van den Born, M., Korving, J., Martens, A.C., Barker, N., van Oudenaarden, A., Clevers, H. Dll1(+) secretory progenitor cells revert to stem cells upon crypt damage. Nat Cell Biol. 14: 1099-1104 (2012)
• Boj, S,F., van Es, J.H.,Huch. M., Li, V.S., Jose, A., Hatzis, P., Mokry, M., Haegebarth, A., van den Born, M., Chambon, P., Voshol, P., Dor, Y., Cuppenm E., Fillat, C., Clevers, H. Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell 151: 1595-1607 (2012)
• Huch, M., Dorrell, C., Boj, S.F., van Es, J.H., van de Wetering, M., Li, V.S.W., Hamer, K., Sasaki, N., Finegold, M.J., Haft, A., Grompe, M., Clevers, H. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494: 247-250 (2013
• Sato, T., Clevers, H.. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Review Science 340: 1190-1194 (2013)
• Clevers, H. The intestinal crypt, a prototype stem cell compartment. Cell. 154: 274-284 (2013)
• Stange, D.E., Koo, B.K., Huch, M., Sibbel, G., Basak, O., Lyubimova, A., Kujalla, P., Bartfeld, S., Koster, J., Geahlen, J.H., Peters, P.J., van Es, J., van de Wetering, M., Mills, J.C., Clevers, H. Differentiated Troy+ chief cells act as ‘reserve’ stem cells to generate all lineages of the stomach epithelium. Cell 155: 357-368 (2013)
• Schwank, G., Koo, B.K., Sasselli, V., Dekkers, J.F., Heo, I., Demircan, T., Sasaki, N., Boymans, S., Cuppen, E., van der Ent, C.K., Nieuwenhuis, E.E., Beekman, J.M., Clevers, H. Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients. Cell Stem Cell 13: 653-658 (2013)
• Ritsma, L., Ellenbroek, S.I., Zomer, A., Snippert, H.J., de Sauvage, F.J., Simons, B.D., Clevers, H., van Rheenen, J. Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature 507: 362-365 (2014)
• Karthaus, W.R., Iaquinta, P.J., Drost, J., Gracanin, A., van Boxtel, R., Wongvipat, J., Dowling, C.M., Gao, D., Begthel, H., Sachs, N., Vries, R.G., Cuppen, E., Chen, Y., Sawyers, C.L., Clevers, H.C. Identification of Multipotent Luminal Progenitor Cells in Human Prostate Organoid Cultures. Cell. 159:163-175 (2014)
• Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M., Ellis, E., van Wenum, M., Fuchs, S., de Ligt, J., van de Wetering, M., Sasaki, N., Boers, S., Kemperman, H., de Jonge, J. IJzermans, J., Niewenhuis, E., Hoekstra, R., Strom, S., Vries, R., van der Laan, L., Cuppen, E., Clevers, H. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160: 299-312 (2015)
• Boj, S.F., Hwang, C.I., Baker, L.A., Chio, I.I., Engle, D.D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M.S., Gracanin, A., Oni, T., Yu, K.H., van Boxtel, R., Huch, M., Rivera, K.D., Wilson, J.P., Feigin, M.E., Öhlund, D., Handly-Santana, A., Ardito-Abraham, C.M., Ludwig, M., Elyada, E., Alagesan, B., Biffi, G., Yordanov, G.N., Delcuze, B., Creighton, B., Wright, K., Park, Y., Morsink, F.H., Molenaar, I.Q., Borel Rinkes, I.H., Cuppen, E., Hao, Y., Jin, Y., Nijman, I.J., Iacobuzio-Donahue, C., Leach, S.D., Pappin, D.J., Hammell, M., Klimstra, D.S., Basturk, O., Hruban RH, Offerhaus GJ, Vries RG, Clevers H, Tuveson DA. Organoid models of human and mouse ductal pancreatic cancer. Cell 160: 324-338 (2015)
• van de Wetering, M., Francies, H.E., Francis, J.M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., McLaren-Douglas, A., Blokker, J., Jaksani, S., Bartfeld, S., Volckman, R., van Sluis, P., Li, V.S.W., Seepo, S., Sekhar Pedamallu, C., Cibulskis, C., Carter, S.L., McKenna, A., Lawrence, M.S., Lichtenstein, L., Stewart, C., Koster, J., Versteeg, R., van Oudenaarden, A., Saez-Rodriguez, J., Vries, R.G.J., Getz, G., Wessels, L., Stratton, M.R., McDermott, U., Meyerson, M., Garnett, M.J., Clevers, H. Prospective derivation of a 'Living Organoid Biobank' of colorectal cancer patients. Cell 161: 933-945 (2015)
• Drost, J., van Jaarsveld, R.H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A.,Sachs, N., Overmeer, R.M., Offerhaus, G.J., Begthel, H. Korving, J., van de Wetering, M., Schwank, G. Logtenberg, M., Cuppen, E., Snippert, H.J., Medema, J.P., Kops, G. J. P. L., Clevers, H. Sequential cancer mutations in cultured human intestinal stem cells. Nature 521: 43-47 (2015)
• Farin, H.F., Jordens, I., Mosa, M.H., Basak, O., Korving, J., Tauriello, D.V.F., de Punder, K., Angers, S., Peters, P.J. Maurice, M.M. and Clevers, H. Visualization of the short-range Wnt gradient in the intestinal stem cell niche. Nature (in press)

References

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