Prof. Johannes (Hans) Carolus Clevers, MD, PhD, Professor of Molecular Genetics at Utrecht University, Principal Investigator at the Hubrecht Institute and the Princess Máxima Center for Pediatric Oncology and Oncode Investigator, in Utrecht, the Netherlands. From March 2022: Head of Roche Pharmaceutical Research and Early Development (pRED).
This is a Science Portrait of Prof. Hans (J.C.) Clevers , Professor of Molecular Genetics at Utrecht University, Principal Investigator at the Hubrecht Institute and the Princess Máxima Center for Pediatric Oncology and Oncode Investigator, in Utrecht, the Netherlands. He will give a presentation at Fujita Health University, by Zoom, on Friday, February 25.
Prof. Clevers is a renowned pioneer and world leader in stem cell and organoid (an artificially grown mass of cells that resembles an organ) research. He has been suggested as a future contender for the Nobel prize, amongst other reasons because of the impact of his publications (link ), and because organoid research (in mice, organoids have already been shown to have regenerative power) may sooner or later be considered deserving of this (link ). Among the many prestigious prizes that he has won so far (see below for a fuller list), are the Breakthrough Prize in Life Sciences in 2013 Keio Medical Science Prize in 2019
Prof. Clevers has been listed as No. 72 of all researchers worldwide based on his h-index score on Google Scholar (link ). Currently, his Google Scholar scores are: h-index = 215, citations = 204941
He has >720 publications, of which 20 in Nature , 23 in Cell , and 13 in Science .
From March 18, Prof. Clevers will have one of the biggest jobs worldwide in biomedical translational research as he has been appointed as the new Head of Roche Pharmaceutical Research and Early Development (pRED) >2000 scientists .
Equally important for us as an audience is that he is a great speaker , always showing beautiful images and videos of a topic close to the heart of all biomedical scientists, namely tissue generation. In his presentation, he will explain to us how organoids can be used to model human diseases and help to find cures. He is also a very nice and friendly person.
For more information about him, see, for example, Wikipedia (where there is a video with interview) or a portrait in Science .
Prof. Clevers belongs to the top of potential speakers, both regarding his scientific achievements and his ability to explain well. So, if you have time, please visit this seminar.
CURRICULUM VITAE
Born 1957 , Son en Breugel, the Netherlands
EDUCATION
1975 – 1982 M.Sc. (“Doctoraal”) in Biology. University of Utrecht
1978 – 1984 M.D. (“Artsexamen”) University of Utrecht
1984 – 1985 Ph.D. (“Promotie”) University of Utrecht
PROFESSIONAL EXPERIENCE:
1985 – 1989 Postdoctoral Fellow, Cox Terhorst Lab at the Dana-Farber Cancer
Institute, Harvard Medical School, Boston MA, USA
1989 – 1991 Assistant Professor, Department of Clinical Immunology, University of
Utrecht
1991 – 2002 Professor and Chairman, Dept. of Immunology, Faculty of Medicine,
University of Utrecht
2002 – 2012 Director of the Hubrecht Institute, Royal Netherlands Academy of Arts
and Sciences
2002 – 2020 Professor in Molecular Genetics at University Medical Center Utrecht
2002 – present Principal Investigator of a research group of ~40 scientists at
Hubrecht Institute, Utrecht
2012 – 2015 President of the Royal Netherlands Academy of Sciences (KNAW),
Amsterdam
2014 – 2020 Chief Scientific Officer of HUB Organoids Technology, Utrecht
2015 – 2019 Chief Scientific Officer/Director Research of the Princess Máxima
Center, Utrecht
2015 – present Principal Investigator at the Princess Máxima Center, Utrecht
2017 – present Oncode Investigator
2020 – present Professor of Molecular Genetics at University Utrecht
HONORARY PROFESSORSHIPS:
2002 – present Central South University, Chang Sha, China
2014 – 2015 TEFAF Oncology Chair, Maastricht
2015 – 2016 Visiting professor, Weizmann Institute, Rehovoth, Israel
2016 – present Distinguished Visiting Professor, University of Hong Kong
2015 Visiting professor, University of Melbourne, Australia
2019 – present Honorary Director, Fudan Organoid Center, Fudan University, Shanghai
2021 Honorary Doctorate Catholic University of Leuven, Belgium
PRIZES, AWARDS
2000 Catharijne-prize for medical research, Utrecht
2001 Award from the European Society for Clinical Investigation, Nice
2001 Spinoza Award of the Netherlands Reserach Council (NWO, Den Haag)
2004 Louis-Jeantet Prize for Medicine, Geneva, Switzerland
2005 The Science and Society Prize, Amsterdam
2005 The French honor of “Chevalier de la Legion d’Honneur” (Netherlands
embassy)
2005 Katharine Berkan Judd Award, New York
2006 Rabbi Shai Shacknai Memorial Prize for Immunology and Cancer Research,
Jerusalem
2008 Josephine Nefkens Prize for Cancer Research (Erasmus MC, Rotterdam)
2008 Meyenburg Cancer Research Award,
Germany
2009 The Queen Wilhelmina Dutch Cancer Society Award, Amsterdam
2010 The United European Gastroenterology Federation (UEGF) Research Prize
2011 The Ernst Jung Medical Award, Germany
2011 Kolff prize, Amsterdam
2012 Association pour la Recherche sur le Cancer (ARC) Léopold Griffuel Prize,
Paris
2012 William Beaumont prize of the American Gastroenterology Association (USA)
2012 The Heineken Prize for Medicine, Amsterdam
2012 Knight in the Order of the Nederlands’ Lion
2013 The Breakthrough Prize in Life Sciences, San Francisco
2014 Massachusetts General Hospital Award in Cancer Research, Massachusetts
2014 Fellow of the AACR Academy, Washington
2014 Struyvenberg European Society for Clinical Investigation (ESCI) medal,
Utrecht
2014 National Icon of the Netherlands, Amsterdam
2015 ISSCR-McEwen Award for Innovation, San Francisco
2016 The Academy Professor Prize of the Royal Netherlands Academy,
Amsterdam
2016 Kazemi Award for Research Excellence in Bio-Medicine, Teheran
2016 The Körber European Science Prize, Germany
2016 Swammerdam medaille, Amsterdam, Netherlands
2016 The Ilse & Helmut Wachter award, Hamburg, Germany
2017 Princess Takamatsu Award of Merit, Tokyo, Japan
2017 Großes Verdienstkreuz mit Stern, Germany
2018 Academia Europaea Erasmus Medal, Barcelona, Spain
2019 Keio Medical Science Prize, Tokyo, Japan
2019 Citation Laureate, Web of Science Group
2021 Pezcoller Foundation-AACR International Award
ELECTED MEMBERSHIPS
1999 Member European Molecular Biology Organisation (EMBO)
2000 Member of the Royal Netherlands Academy of Sciences (KNAW)
2009 Member of the Academia Europaea
2012 Member of the American Academy of Arts and Sciences
2012 Member of the ‘Koninklijke Hollandsche Maatschappij der Wetenschappen’
(Royal Netherlands Society of Sciences and Humanities)
2014 International member of the National Academy of Sciences of the USA
2016 Member of the Academie des Sciences de I’Institut de France
2017 Member of the Orden Pour le Mérite für Wissenschaften und Künste,
Germany
2019 Member of the New York Academy of Sciences, New York
2019 Foreign Member of the Royal Society of London
2019 Honorary Fellowship of the Royal Society of Edinburgh,
Scotland’s National Academy of Science and Letters
BOARDS
2005 – 2015 Member of the Scientific Advisory Board of Swiss Institute for
Experimental Cancer Research, Lausanne
2006 – 2008 President of the International Society of Differentiation (ISD)
2007 – 2010 Member of the National Scientific Advisory Board NKI-AVL,
Amsterdam
2012 – 2015 Member of the Board of the American Association of Cancer Research
2015 – present Member of the Scientific Advisory Board of the Institute of Molecular
Pathology, Vienna
2016 – 2020 Member of the Scientific Advisory Board of Kallyope, New York
2016 – present Member of the Scientific Advisory Board of the Francis Crick Institute,
London
2016 – 2021 Member of the Scientific Advisory Board of Decibel Therapeutics,
Boston
2016 – present Member of the Scientific Advisory Board of Surrozen, San Francisco
2017 – 2018 President of the International Society for Stem Cell Research (ISSCR)
2018 – present Member of the Scientific Advisory Board of Merus, Utrecht
2018 – present Scientific advisor Life Science Partners, Amsterdam
2019 – present Non-executive member of the Board of Directors of Roche Holding
Ltd, Basel
2020 – 2021 Member of the Scientific Advisory Board of Volestra Therapeutic Inc.,
New York
2020 – present Chair of the Scientific Advisory Board DImed Inc., Shanghai
2020 – present Chair of the Scientific Advisory Board of Xilis, at Duke University (NC)
EDITORIAL BOARDS
2004 – present Member of the Editorial Board of EMBO Journal
2008 – present Member of Editorial Board of Disease Models & Mechanisms (DMM)
2009 – present Member of the Editorial Board of Cell
2012 – present Member of the Editorial Board of Stem Cell Reports
2013 – present Member of the Editorial Board of Cell Stem Cell
2014 – present Member of the Editorial Committee of Annual Review of Cancer
Biology
2020 – present Member of Scientific Advisory Board of Med (Cell Press)
PUBLICATIONS
Selected papers (out of ~720 peer-reviewed)
1. van de Wetering, M., Oosterwegel, M., Dooijes, D. and Clevers, H., Identification and cloning of TCF-1, a T cell-specific transcription factor containing a sequence-specific HMG box. EMBO J. 10:123-132 (1991)
2. 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. An HMG box containing T-cell factor required for thymocyte differentiation. Nature 374:70-74 (1995)
3. Schilham, M., Oosterwegel, M., Moerer, P., Jing, Y., de Boer, P., van de Wetering, M., Verbeek, 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)
4. 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)
5. 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)
6. 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)
7. 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)
8. 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)
9. 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)
10. 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)
11. Korswagen, R., Herman, M. and Clevers, H. Separate beta-catenins mediate Wnt signaling and cadherin adhesion in C. elegans. Nature 406:527-532 (2000)
12. Bienz, M. and Clevers, H. Linking colorectal cancer to Wnt signaling. Cell 103:311-320 (2000)
13. 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. and Clevers, H. The beta catenin/TCF4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111:241-250 (2002)
14. 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. and 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)
15. Hurlstone, A.F., Haramis, A.P., Wienholds, E., Begthel, H., Korving, J., van Eeden, F., Cuppen, E., Zivkovic, D., Plasterk, R.H. and Clevers, H. The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature 425:633-637 (2003)
16. Baas, A.F., Kuipers, J., van der Wel, N.N., Batlle, E., Koerten, H.K., Peters, P.J. and Clevers, H. Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Cell 116:457-466 (2004)
17. Haramis, A.P., Begthel, H., van den Born, M., van Es, J., Jonkheer, S., Offerhaus, G.J. and Clevers, H. De novo crypt formation and Juvenile Polyposis upon BMP inhibition. Science 303:1684-1686 (2004)
18. Radtke, F. and Clevers, H. Self-renewal and cancer of the gut: Two sides of a coin. Review Science 307:1904-1909 (2005)
19. Reya, T. and Clevers, H. Wnt signalling in stem cells and cancer. Review. Nature 434:843-850 (2005)
20. 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. and Clevers H. Notch pathway/γ-secretase inhibition turns proliferative cells in intestinal crypts and neoplasia into Goblet cells. Nature 435:959-963 (2005)
21. 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. and Clevers, H. EphB activity suppresses colorectal cancer progression. Nature 435:1126-1130 (2005)
22. Clevers, H. Wnt/β-catenin signaling in development and disease, Review Cell 127:469-480 (2 006)
23. 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. and Clevers, H. Identification of stem cells in small intestine and colon by the marker gene LGR5. Nature 449:1003-1007 (2007)
24. 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)
25. 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. and Clevers, H. Crypt Stem Cells as the Cells-of-Origin of Intestinal Cancer. Nature 457:608-611 (2009)
26. 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)
27. 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)
28. 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. and 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)
29. 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. and Clevers H. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 327:1385-1389 (2010)
30. 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)
31. 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. and Clevers, H. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476:293-297 (2011)
32. Sato T., Stange, D.E., Ferrante, M., Vries R.G., Van Es, J.H., van den Brink, S., van Houdt, W.J., Pronk, A, van Gorp, J., Siersema, P.D. and Clevers, H. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141: 1762-1772 (2011)
33. 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. and Clevers, H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469:415-418 (2011)
34. 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)
35. 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 Clevers, H. Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488:665-669 (2012)
36. Schepers, A.G., Snippert, H.J., Stange, D.E., van den Born, M., van Es, J.H., van de Wetering, M. and Clevers, H. Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas. Science 337:730-735 (2012)
37. 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. and Clevers, H. Dll1(+) secretory progenitor cells revert to stem cells upon crypt damage. Nat Cell Biol. 14:1099-1104 (2012)
38. 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. and Clevers, H. Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell 151:1595-1607 (2012)
39. 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. and Clevers, H. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494:247-250 (2013)
40. Sato, T. and Clevers, H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Review Science 340:1190-1194 (2013)
41. Clevers, H. The intestinal crypt, a prototype stem cell compartment. Cell 154:274-284 (2013)
42. 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. and Clevers, H. Differentiated Troy+ chief cells act as ‘reserve’ stem cells to generate all lineages of the stomach epithelium. Cell 155:357-368 (2013)
43. 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. and 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)
44. Ritsma, L., Ellenbroek, S.I., Zomer, A., Snippert, H.J., de Sauvage, F.J., Simons, B.D., Clevers, H. and van Rheenen, J. Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature 507:362-365 (2014)
45. 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. and Clevers, H. Identification of Multipotent Luminal Progenitor Cells in Human Prostate Organoid Cultures. Cell 159:163-175 (2014)
46. 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. and Clevers, H. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160:299-312 (2015)
47. van de Wetering, M., Francies, H.E., Francis, J.M., Bounova, G., Lorio, 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 and Clevers, H. Prospective derivation of a ‘Living Organoid Biobank’ of colorectal cancer patients. Cell 161:933-945 (2015)
48. 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)
49. 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. and Clevers, H. Sequential cancer mutations in cultured human intestinal stem cells. Nature 521:43-47 (2015)
50. 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 530:340-343 (2016)
51. Clevers, H. Modeling development and disease with organoids. Cell 165:1586-1597 (2016)
52. Drost, J., van Boxtel, R., Blokzijl, F., Mizutani, T., Sasaki, N., Sasselli, V., de Ligt, J., Behjati, S., Grolleman, J.E., van Wezel, T., Nik-Zainal, S., Kuiper, R.P., Cuppen, E. and Clevers, H. Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer. Science 358:234-238 (2017)
53. Sachs, N., de Ligt, J., Kopper, O., Gogola E., Bounova G., Weeber, F., Balgobind, A.V., Wind, K., Gracanin, A., Begthel, H., Korving, J., van Boxtel, R., Duarte, A.A., Lelieveld, D., van Hoeck, A., Ernst, R.F., Blokzijl, F., Nijman, I.J., Hoogstraat, M., van de Ven, M., Egan, D.A., Zinzalla, V., Moll, J., Boj, S.F., Voest, E.E., Wessels, L., van Diest, P.J., Rottenberg, S., Vries, R.G.J., Cuppen, E. and Clevers, H. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. Cell 172:373-386 (2018)
54. Roerink, S., Sasaki, N., Lee-Six, H., Young, M., Alexandrov, L., Behjati, S., Mitchell, T., Grossmann, S., Lightfoot, H., Egan, D., Pronk, A., Smakman, N., van Gorp, J., Anderson, E., Gamble, S., Alder, C., van de Wetering, M., Campbell, P., Stratton, M. and Clevers, H. Intra-tumour diversification in colorectal cancer at the single-cell level. Nature 556:457-462 (2018)
55. Heo, I., Dutta, D., Schaefer, D.A., Lakobachvili, N., Artegiani, B., Sachs, N., Boonekamp, K.E., Bowden, G., Hendrickx, A.P.A., Willems, R.J.L., Peters, P.J., Riggs, M.W., O’Connor, R. and Clevers, H. Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat Microbiol. 3:814-823 (2018)
56. Hu, H., Gehart, H., Artegiani, B., Löpez-Iglesias, C., Dekkers, F., Basak, O., van Es, J., Chuva de Sousa Lopes, S.M., Begthel, H., Korving, J., van den Born, M., Zou, C., Quirk, C., Chiriboga, L., Rice, C.M., Ma, S., Rios, A., Peters, P.J., de Jong, Y.P. and Clevers, H. Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids. Cell 175:1591-1606 (2018)
57. Tuveson, D. and Clevers, H. Cancer modeling meets human organoid technology. Science 364:952-955 (2019)
58. Gehart, H., van Es, J.H., Hamer, K., Beumer, J., Kretzschmar, K., Dekkers, J.F., Rios, A. and Clevers, H. Identification of Enteroendocrine Regulators by Real-Time Single-Cell Differentiation Mapping. Cell 176:1158-1173 (2019)
59. Kopper , O., de Witte, C.J., Lõhmussaar, K., Valle-Inclan, J.E., Hami, N., Kester, L., Balgobind, A.V., Korving, J., Proost, N., Begthel, H., van Wijk, L.M., Revilla, S.A., Theeuwsen, R., van de Ven, M., van Roosmalen, M.J., Ponsioen, B., Ho, V.W.H., Neel, B.G., Bosse, T., Gaarenstroom, K.N., Vrieling, H., Vreeswijk, M.P.G., van Diest, P.J., Witteveen, P.O., Jonges, T., Bos, J.L., van Oudenaarden, A., Zweemer, R.P., Snippert, H.J.G., Kloosterman, W.P. and Clevers, H. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. Nat Med. 25:838-849 (2019)
60. Tuveson, D. and Clevers, H. Cancer modeling meets human organoid technology. Science 364:952-955 (2019)
61. Post, Y., Puschhof, J., Beumer, J., Kerkkamp, H.M., de Bakker, M.A.G., Slagboom, J., de Barbanson, B., Wevers, N.R., Spijkers, X.M., Olivier, T., Kazandjian, T.D., Ainsworth, S., Iglesias, C.L., van de Wetering, W.J., Heinz, M.C., van Ineveld, R.L., van Kleef, R.G.D.M., Begthel, H., Korving, J., Bar-Ephraim, Y.E., Getreuer, W., Rios, A.C., Westerink, R.H.S., Snippert, H.J.G., van Oudenaarden, A., Peters, P.J., Vonk, F.J., Kool, J., Richardson, M.K., Casewell, N.R. and Clevers, H. Snake Venom Gland Organoids. Cell 180:233-247 (2020)
62. Artegiani, B., Hendriks, D., Beumer, J., Kok, R., Zheng, X., Joore, I., Chuva de Sousa Lopes, S., van Zon, J., Tans, S. and Clevers, H. Fast and efficient generation of knock-in human organoids using homology-independent CRISPR-Cas9 precision genome editing. Nat Cell Biol. 22:321-331 (2020)
63. Pleguezuelos-Manzano, C., Puschhof, J., Huber, A.R., van Hoeck, A., Wood, H.M., Nomburg, J., Gurjao, C., Manders, F., Dalmasso, G., Stege, P.B., Paganelli, F.L., Geurts, M.H., Beumer, J., Mizutani, T., van der Linden, R., van Elst, S.; Genomics England Research Consortium, Top J., Willems, R.J.L., Giannakis, M., Bonnet, R., Quirke, P., Meyerson, M., Cuppen, E., van Boxtel, R. and Clevers, H. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature 580:269-273 (2020)
64. Geurts, M.H., de Poel, E., Amatngalim, G.D., Oka, R., Meijers, F.M., Kruisselbrink, E., van Mourik, P., Berkers, G., de Winter-de Groot, K.M., Michel, S., Muilwijk, D., Aalbers, B.L., Mullenders, J., Boj, S.F., Suen, S.W.F., Brunsveld, J.E., Janssens, H.M., Mall, M.A., Graeber, S.Y., van Boxtel, R., van der Ent, C.K., Beekman, J.M. and Clevers, H. CRISPR-Based Adenine Editors Correct Nonsense Mutations in a Cystic Fibrosis Organoid Biobank. Cell Stem Cell 26:503-510 (2020)
65. Lamers, M.M., Beumer, J., van der Vaart, J., Knoops, K., Puschhof, J., Breugem, T.I., Ravelli, R.B.G., van Schayck, J.P., Mykytyn, A.Z., Duimel, H.Q., van Donselaar, E., Riesebosch, S., Kuijpers, H.J.H., Schipper, D., van de Wetering, W.J., de Graaf, M., Koopmans, M., Cuppen, E., Peters, P.J., Haagmans, B.L. and Clevers, H. SARS-CoV-2 productively Infects Human Gut Enterocytes. Science 369:50-54 (2020)
66. Beumer, J., Puschhof, J., Bauzá-Martinez, J., Martínez-Silgado, A., Elmentaite, R., James, K.R., Ross, A., Hendriks, D., Artegiani, B., Busslinger, G., Ponsioen, B., Andersson-Rolf, A., Saftien, A., Boot, C., Kretzschmar, K., Geurts, M.H., Bar-Ephraim, Y.E., Pleguezuelos Manzano, C., Post, Y., Begthel, H., van der Linden, F., Lopez-Iglesias, C., van de Wetering, W.J., van der Linden, R., Peters, P.J., Heck, A.J.R., Goedhart, J., Snippert, H., Zilbauer, M., Teichmann, S.A., Wu, W. and Clevers, H. High Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells. Cell 181:1291-1306 (2020)
67. Lohmussaar K., Oka R., Espejo Valle-Inclan J., Veersema S., […] van Boxtel R., Clevers H. Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer. Cell Stem Cell 28:1-17 (2021)
68. Bannier-Hélaouët M., Post Y., Korving J. […] Imhoff S., Clevers H. Exploring the human lacrimal gland using organoids and single-cell sequencing. Cell Stem Cell 28:1-12 (2021)
69. Lamers M.M., Beumer J., van der Vaart J. […] Haagmans, B.L., Clevers H. SARS-CoV-2 productively Infects Human Gut Enterocytes. Science 369:50-54 (2021)
