Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M.A., Ellis, E., van Wenum, M., Fuchs, S., de Ligt, S., van de Wetering, M., Sasaki, N., Boers, S.J., Kemperman, H., de Jonge, J., Ijzermans, J.N.M., Niewenhuis, E.E.S., Hoekstra, R., Strom, S., Vries, R.G.J., van der Laan, L.J.W., Cuppen, E., Clevers, H. 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. Ritsma, L., Ellenbroek, S.I., Zomer, A., Snippert, H.J., de Sauvage, F.J., Simons, B.D., Clevers, H., van Rheenen, J. 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. Oncode Institute More than 10 years after the cultivation of the first organoid – at the Hubrecht Institute by Toshiro Sato in the group headed by Hans Clevers – the path to commercial applications is open. 2019 – present  Non-executive member of the Board of Directors of Roche Holding Ltd, Basel Lgr5 crypt stem cells behave in unanticipated ways: Against common belief, they divide constantly. 10 Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. All these recruits have secured an ERC Starter or Consolidator grant demonstrating that their potential is also recognized by this major funding agency. The tumor suppressor protein APC forms the core of a cytoplasmic complex which binds ß-catenin and targets it for degradation in the proteasome. 2007 – 2010      Member of the National Scientific Advisory Board NKI-AVL, Amsterdam Forskolin opens the CFTR channel, resulting in rapid swelling of normal organoids. View ORCID Profile Hans Clevers 2, †, ‡ 1 Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands. Hans Clevers (Hubrecht Institute): "These organoids contain the cells of the human intestinal lining, making them a compelling model to investigate infection by SARS-CoV-2." This was echoed by an independent scientific evaluation: “In the opinion of the committee, the quality of science done at the Hubrecht Institute is equal to that of the best research institutions in the world”. During the last five years, the Hubrecht Institute has been very successful in attracting young talented group leaders who started a tenure track at our institute. 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., Clevers, H. The Wnt/beta-catenin pathway regulates cardiac valve formation. 2006 – 2008      President of the International Society of Differentiation (ISD) He also serves as Director of the Princess Maxima Center for Pediatric Oncology. 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. Nature Biotechnology, 37:303-313 (2019), 58)          Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Prof. Dr. Alfonso Martinez Arias, University of Cambridge, Cambridge 11 Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, Utrecht, The Netherlands h.clevers@hubrecht.eu. It promotes quality in science and scholarship and strives to ensure that Dutch scholars and scientists contribute to cultural, social and economic progress. The Hubrecht Institute is a lively, international research community that is supported by high quality services. About Us. Review Johannes Carolus (Hans) Clevers (born 27 March 1957) is Principal Investigator at the Hubrecht Institute for Developmental Biology and Stem Cell Research (KNAW) and the Princess Máxima Center for Pediatric Oncology, Professor at Utrecht University and Oncode Investigator. Hubrecht Organoid Technology (HUB) was founded by the Hubrecht Institute, the University Medical Center Utrecht, and the Royal Netherlands Academy of Arts and Sciences (KNAW). The Hubrecht Institute has a tight collaboration with the UU on multiple levels: there is a lot of scientific collaboration, several PI’s are appointed as professor at the UU, all Hubrecht PhD students participate in the Graduate School of Life Sciences and various Master students perform their internships at one of the Hubrecht groups. 2017               Member of the Orden Pour le Mérite für Wissenschaften und Künste, Germany Research groups. Researchers from the UMC Utrecht work alongside researchers from the Hubrecht Institute in this new building. European Molecular Biology Laboratory (EMBL) 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., Clevers, H. Long-term culture of genome-stable bipotent stem cells from adult human liver. 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., Clevers, H. Dll1(+) secretory progenitor cells revert to stem cells upon crypt damage. From 1991-2002 Hans Clevers was Professor in Immunology at the University Utrecht and, since 2002, Professor in Molecular Genetics. 2012    Association pour la Recherche sur le Cancer (ARC) Léopold Griffuel Prize, Paris 5,898. The Hubrecht is a highly dynamic, diverse and young institute where the average age of the researchers is around 30 and more than 30 different nationalities are represented. 2016               Member of the Academie des Sciences de I’Institut de France 2014 – present  Breakthrough Prize in Life Sciences, San Francisco This technology is based on the discovery of the LGR5 positive adult epithelial stem cell, first identified in the intestine by the group headed by Prof. Hans Clevers. The direct cloning of multiple individual cells from primary tumors allows molecular and functional analysis of tumor heterogeneity with an unprecedented resolution (54). 2019 – present  Foreign Advisory Board Member of Consortium for Neogenetic Medicine, Tokyo, 1999               Member European Molecular Biology Organisation (EMBO) Science 364:952-955 Review (2019), Lamers MM, Beumer J, van der Vaart J [...] Haagmans, BL, Clevers H, Post Y, Puschhof J, Beumer B [...] Casewell NR, Clevers H, Pleguezuelos-Manzano C, Puschhof J, Rosendahl A [...] van Boxtel R, Clevers H, Kopper O, de Witte, CJ [...] Kloosterman WP, Clevers H, Schutgens F, Rookmaaker MB [...] Verhaar MC, Clevers H, Gehart H, van Es J, [...] Rios A, and Clevers H, Hu H, Gehart H [...] de Jong YP, Clevers H, Roerink SF, Sasaki N [...] Stratton MR, Clevers H, Sachs N, de Ligt J [...] Cuppen E, Clevers H, Drost J, van Boxtel R [...] Cuppen E, Clevers H. 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. Farin, H.F., Jordens, I., Mosa, M.H., Basak, O., Korving, J., Tauriello, D.V.F., de Punder, K., Angers, S., Peters, P.J. 2016    The Ilse & Helmut Wachter award, Hamburg, Germany This allowed the institute to grow into an internationally renowned research institute and facilitated the link with (pre)clinical research. 10 Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. ); a.vanoudenaarden{at}hubrecht.eu (A.v.O.) Utrecht Life Sciences is a platform that supports collaboration and innovation. 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. Independent work by the Feng Cong lab has first shown that R-spondin, when bound to Lgr5, captures and inactivates RNF43/ZNRF3. Maurice, M.M. A springboard for senior group leaders. In APC-deficient colon carcinoma cells, we demonstrated that ß-catenin accumulates and is constitutively complexed with the TCF family member TCF4, providing a molecular explanation for the initiation of colon cancer (5). To this end, we founded the non-for-profit HUB foundation which currently builds a biobank of all 1500 Dutch CF patients funded by our national insurance companies. Cited by. Gijs van den Brink. The Hubrecht aims to be a springboard for talent and offers its employees the opportunity for personal and professional development, through a wide variety of workshops and courses, including those organized by our mother organization the Royal Netherlands Academy of Arts and Sciences (KNAW). Hubrecht Organoid Technology. Dr. Clevers is a Professor of Molecular Genetics at Hubrecht Institute, Utrecht, The Netherlands. 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. 17 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands; Cancer Genomics Netherlands, Oncode Institute, 3584 CG Utrecht, the Netherlands. These epithelial organoid cultures are genetically and phenotypically extremely stable, allowing transplantation of the cultured offspring of a single stem cell, as well as disease modeling by growing organoids directly from diseased patient tissues (31, 46, 53). The Princess Máxima Center has open her own new hospital and research building at the Utrecht Science Park in May 2018. Dolf Weijers: roots of the future. 2 Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht, Utrecht, Netherlands. Cell 116: 457-466 (2004), 17)           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. Research at the Hubrecht Institute is pioneering in developmental and stem cell biology. and Hans Clevers. 2019    Honorary Fellow of the Royal Society of Edinburgh (UK) Currently, there are more than 70 PhD students at the Hubrecht Institute. Science 327: 1385-1389 (2010), 30)           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. 2017 – present  Francqui Prize, Bruxelles 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., Clevers, H. Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients. Prof. Dr. Michiel Vermeulen, Radboud University, Nijmegen. Review. Nature Genetics 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. Related genes exist in genomes throughout the animal kingdom.We have shown in frogs (4), flies (7) and worms (11) that the TCF proteins constitute the effectors of the canonical Wnt pathway. 2016    The Körber European Science Prize, Germany The related Lgr6 marks multipotent skin stem cells (29). ↵ * Corresponding author. M., van den Born, M., Begthel, H., Vries, R.G., Stange, D.E., Toftgård, R., Clevers, H. 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. van der Flier, L.G., van Gijn, M.E., .., and Clevers, H. 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. Jaks V., Barker N., Kasper M., van Es J.H., Snippert H.J., Clevers H., Toftgård, R. Barker, N, van Es, J.H., Kuipers, J., Kujala P., van den Born, M., Cozijnsen, M., Korving, J., Begthel, H., Peters, P.C., and Clevers, H. 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. 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. Haramis A.P., Begthel H., van den Born M., van Es J., Jonkheer S., Offerhaus G.J., Clevers H. Baas A.F., Kuipers J., van der Wel N.N., Batlle E., Koerten H.K., Peters P.J., Clevers H.C. Hurlstone A.F., Haramis A.P., Wienholds E., Begthel H., Korving J., Van Eeden F., Cuppen E., Zivkovic D., Plasterk R.H., Clevers H. Battle, 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. 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. Korswagen, R., Herman, M. and Clevers, H. Roose, J., Huls, G., van Beest, M., Moerer, P., van der Horn, K., Goldschmeding, R., Logtenberg, T., and Clevers, H. Roose, J., Molenaar, M., Peterson, J., Hurenkamp, J., Brantjes, H., Moerer, P., van de Wetering, M., Destree, O., and Clevers, H. Korinek, V., Barker, N., Moerer, P., van Donselaar, E., Huls, G., Peters, P.J. 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. It promotes quality in science and scholarship and strives to ensure that Dutch scholars and scientists contribute to cultural, social and economic progress. As a patient-centered organization, its 11,000 employees are dedicated to prevent disease, improve healthcare, develop new treatment methods and refine existing ones, with quality and patient safety as cornerstones. Towards a better treatment . 2017    Princess Takamatsu Award of Merit, Tokyo The Hubrecht Institute is part of the Royal Netherlands Academy of Arts and Sciences (KNAW) and has a special partnership with the UMC Utrecht, Utrecht University, Princess Máxima Center for pediatric oncology, the European Molecular Biology Laboratory (EMBL) and Oncode Institute. Prof. Dr. Edith Heard, EMBL, Heidelberg 2020 – present  Chair of the Scientific Advisory Board DImed Inc., Shanghai 2012    Knight in the Order of the Netherlands’ Lion Nature 469: 415-418 (2011). Hans Clevers ‡ Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands. 2012               Member of the American Academy of Arts and Sciences Utrecht University is an international research university of the highest quality and the alma mater of many leading names, academics and scientists who have made an important contribution to the quality of society. 2015    ISSCR-McEwen Award for Innovation 5 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht , Utrecht, the Netherlands. The Clevers group studies the biology of Wnt signaling in tissue turnover and in cancer. Upon Wnt signaling, ß-catenin binds and activates nuclear TCFs by providing a trans-activation domain. Ushering in a new era of personalised medicine and drug development, Dutch molecular geneticist Hans Clevers and teams at the Hubrecht Institute and the University Medical Center (UMC) in Utrecht pioneered so-called "organoids". Research at the Hubrecht Institute focuses on developmental biology and stem cells at the organismal, cellular, and molecular level. In the UMC Utrecht, research is concentrated in six programs with each a limited number of disease targets. 2014    TEFAF Oncology Chair 2014, Maastricht 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., Clevers H.  Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. EMBO J. Hubrecht Institute. 2020 – present  Member of the Board of Directors of Genentech, South San Francisco This is reflected by our broad introduction program, yearly evaluation meetings and regular drinks and outings to improve integration, collaboration and relaxation. 2006    Rabbi Shai Shacknai Memorial Prize for Immunology and Cancer Research, Jerusalem The Hubrecht Institute is situated on Utrecht Science Park (USP), which provides a home base for Utrecht University, University Medical Center Utrecht, HU Utrecht University of Applied Sciences and various small and large companies. 2001    Award from the European Society for Clinical Investigation The Clevers group studies the biology of Wnt signaling in tissue turnover and in cancer. Two other Wnt target genes, RNF43 and ZNRF3, encode stem cell-specific E3 ligases that downregulate Wnt receptors. A center for interdisciplinary biomedical research. Patient-derived organoids hold promise to predict drug response in a personalized fashion and open up new avenues for regenerative medicine and, in combination with genome editing technology, for gene therapy. People are our most valuable asset and we appreciate every employee for their contribution to the success of the institute. Genetic Background Generation; F?+F23 (2020-01-20 00:00:00) Gt(ROSA)26Sor tm1(CAG-Brainbow2.1)Cle. Wnt Intestine Organoid Adult stem cell. Around 280 people from more than 30 different countries work at the Hubrecht Institute for Developmental Biology and Stem Cell Research. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. As a patient-centered organization, its 11,000 employees are dedicated to prevent disease, improve healthcare, develop new treatment methods and refine existing ones, with quality and patient safety as cornerstones. Since 2008, the Hubrecht Institute is affiliated with University Medical Center Utrecht (UMC Utrecht), which belongs to the largest public healthcare institutions in the Netherlands and is an internationally leading healthcare provider, medical school and research institute that is exciting for its people, attractive to talent and embodies a culture of teamwork, innovation, sustainability and a competitive spirit. And Clevers, H. 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 . Stem cells and organoids Hans Clevers became famous with his stem-cell research into healthy and sick intestines. 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