The research groups operate in an independent manner and scientific quality is guaranteed by yearly internal evaluations and by site visit committees every six years according to the Standard Evaluation Protocol (SEP). In mammals, physiological Wnt signaling is intimately involved with the biology of adult stem cells and self-renewing tissues (18,19). Utrecht University (UU) USP is a vibrant and exciting place to study and work. Hans Clevers is group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research and at the Princess Máxima Center for Pediatric Oncology. 10 The Princess Maxima Center for Pediatric Oncology, Utrecht, … 2019    Citation Laureate, Web of Science Group, 2008 – 2015      Louis Jeantet Prize, Geneva E-mail: h.clevers{at}hubrecht.eu ↵ * These authors contributed equally to this work. 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. 2014    TEFAF Oncology Chair 2014, Maastricht Oncode Institute and Clevers, H. Depletion of epithelial stem cell compartments in the small intestine of mice lacking Tcf 4. 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. 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., van Rheenen, J. Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. This allowed the institute to grow into an internationally renowned research institute and facilitated the link with (pre)clinical research. Developmental Biology and Stem Cell Research UMC Utrecht ↵ ‡ To whom correspondence should be addressed. Maurice, M.M. 2014    Fellow of the AACR Academy Verified email at hubrecht.eu - Homepage. 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. The Hubrecht Institute is a research institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), situated on Utrecht Science Park. This is reflected by our broad introduction program, yearly evaluation meetings and regular drinks and outings to improve integration, collaboration and relaxation. Hubrecht Organoid Technology or HUB was founded around Organoid Technology. Independent work by the Feng Cong lab has first shown that R-spondin, when bound to Lgr5, captures and inactivates RNF43/ZNRF3. In the absence of Wnt signaling, we found that Tcf factors associate with proteins of the Groucho family of transcriptional repressors to repress target gene transcription (9). and Hans Clevers. Hubrecht Institute - Utrecht. And Clevers, H. Xtcf-3 Transcription factor mediates beta-catenin-induced axis formation in xenopus embryos. 2006 – 2008      President of the International Society of Differentiation (ISD) Research at the Hubrecht Institute focuses on developmental biology and stem cells at the organismal, cellular, and molecular level. 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. 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". Among other things, a celebratory issue of Developmental Biology was published. Science 340: 1190-1194 (2013), 41)           Clevers, H. The intestinal crypt, a prototype stem cell compartment. Hans Clevers (Hubrecht Institute) states: "These organoids contain the cells of the human intestinal lining, making them a compelling model to investigate infection by SARS-CoV-2." Developing and transferring novel biomedical methods and technology. 2014 – 2015      TEFAF Oncology Chair, Maastricht 5 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht , Utrecht, the Netherlands. 2018    Academia Europaea Erasmus Medal, Barcelona, Spain [email protected] The KNAW is the forum, conscience, and voice of the arts and sciences in the Netherlands. and Clevers, H. Visualization of the short-range Wnt gradient in the intestinal stem cell niche. A springboard for senior group leaders. Science  358: 234-238 (2017). About Us. A magnet for young talent. Hans Clevers is professor of Molecular Genetics at Utrecht University and the UMC Utrecht, Principal Investigator at the Hubrecht Institute (KNAW) and the Princess Máxima Center for Pediatric Oncology and Oncode Investigator.. 53)           Sachs N, de Ligt J, Kopper O, Gogola E, Bounova G, Weeber F, Balgobind AV, Wind K, Gracanin A, Begthel H, Korving J, van Boxtel R, Duarte AA, Lelieveld D, van Hoeck A, Ernst RF, Blokzijl F, Nijman IJ, Hoogstraat M, van de Ven M, Egan DA, Zinzalla V, Moll J, Boj SF, Voest EE, Wessels L, van Diest PJ, Rottenberg S, Vries RGJ, Cuppen E, Clevers H. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. A breeding ground for spin off companies. 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. From 2002-2012 he was director of the Hubrecht Institute in Utrecht and from 2012-2015 he was President of the Royal … 2001    Award from the European Society for Clinical Investigation The Hubrecht Institute is one of the fifteen outstanding national research institutes of the Royal Netherlands Academy of Arts and Sciences (KNAW). The cornerstones of Oncode are excellent research, intensive cooperation and bringing new treatments faster to the clinic. Presently, the Hubrecht Institute supports 23 research groups with a total of around 280 employees. 55)           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., Clevers H. Long-term expansion of functional mouse and human hepatocytes as 3D organoids 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. 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. The Hubrecht Institute collaborates with numerous laboratories, internationally, nationally and locally, always aiming to improve our research. EMBO J. 3584 CT Utrecht 2017 – present  Francqui Prize, Bruxelles During the last five years this interdisciplinary approach strengthened significantly. Clevers was the first to identify living stem cells in the intestine and is one of the world's leading researchers on adult stem cells, their role in cancer and their potential for regenerative therapy. Contact. Identification and cloning of TCF-1, a T cell-specific transcription factor containing a sequence-specific HMG box. 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. 2016    Kazemi Award for Research Excellence in Bio-Medicine The Princess Máxima Center has open her own new hospital and research building at the Utrecht Science Park in May 2018. 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. Nature 374: 70-74 (1995), 3)              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. Reads . 19. Royal Netherlands Academy of Arts and Sciences (KNAW) Researchers from the group of Hans Clevers at the Hubrecht Institute have modeled the development and progression of high-grade serous ovarian cancer in mini-versions of the female reproductive organs of the mouse. 2019    Honorary Fellow of the Royal Society of Edinburgh (UK) 2015 – present  Principal Investigator at the Princess Máxima Center, Utrecht The Hubrecht Institute is one of the fifteen outstanding national research institutes of the Royal Netherlands Academy of Arts and Sciences (KNAW). Prof. Dr. James Sharpe, EMBL, Barcelona 54)           Roerink S.F., Sasaki N., Lee-Six H., Young M.D., Alexandrov L.B., Behjati S., Mitchell T.J., Grossmann S., Lightfoot H., Egan D.A., Pronk A., Smakman N., van Gorp J., Anderson E., Gamble S.J., Alder C., van de Wetering M., Campbell P.J., Stratton M.R., Clevers H. Intra-tumour diversification in colorectal cancer at the single-cell level. 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. 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., Clevers, H. Beta- catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. 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., Clevers, H. EphB activity suppresses colorectal cancer progression. Stem cells and organoids Hans Clevers became famous with his stem-cell research into healthy and sick intestines. 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. 9 Hubrecht Organoid Technology, Utrecht, The Netherlands. 2019 – present  Honorary Director, Fudan Organoid Center, Fudan University, Shanghai 2011    Kolff prize, Amsterdam 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. From Utrecht Central Station, it takes only 30 min to get to Amsterdam airport, Schiphol, an international hub for most major airlines. In a collaboration with the Cystic Fibrosis clinic in Utrecht, a functional assay was established for the CFTR channel using rectal organoids. He is also University Professor at the University Utrecht and Oncode Investigator. In this video, Hans Clevers summarizes the use of organdies in cancer research. 2012 – 2015      Member of the Board of the American Association of Cancer Research Finally, organoids (as first described by Sasai for pluripotent stem cells and by us for adult stem cells) are rapidly gaining ground as research tools in a wide range of scientific disciplies including basic developmetal and cell biology, infectiology, toxicology and research on hereditary diseases and cancer. 9 Oncode Institute, Utrecht, the Netherlands. The institute encompasses 23 research groups that perform fundamental, multidisciplinary research on healthy and diseased cells, tissues and organisms. 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. Research at the Hubrecht Institute is pioneering in developmental and stem cell biology. 2005    The French honor of “Chevalier de la Legion d’Honneur” Amongst the Wnt target genes, we found the Lgr5 gene to be unique in that it marks small cycling cells at crypt bottoms. About Us. 2017                     Kovalenko Medal, National Academy of Sciences Washington, 2002 – present  Central South University, Chang Sha, China Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Publications 19. The Hubrecht Institute provides an infrastructure that embeds the group in an efficient facility support so that group leaders can focus on the research. All these recruits have secured an ERC Starter or Consolidator grant demonstrating that their potential is also recognized by this major funding agency. We were the first to link Wnt signaling with adult stem cell biology, when we showed that TCF4 gene disruption leads to the abolition of crypts of the small intestine (8), and that TCF1 gene knockout severely disables the stem cell compartment of the thymus (2). Publications. 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., Clevers H. Notch pathway/γ-secretase inhibition turns proliferative cells in intestinal crypts and neoplasia into Goblet cells. Cell 88, 789-799 (1997), 8)              Korinek, V., Barker, N., Moerer, P., van Donselaar, E., Huls, G., Peters, P.J. By time-resolved single cell sequening using a new molecular timer allele, the transcriptional hierarchy of the various enteroendocrine lineages was mapped (56). The Hubrecht Institute further expanded in 2015 with a new laboratory building that was attached to the old building. Review Dolf Weijers. It promotes quality in science and scholarship and strives to ensure that Dutch scholars and scientists contribute to cultural, social and economic progress. 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. 2020 – present  Member of the Board of Genentech, South San Francisco 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. Stem cells and organoids Hans Clevers became famous with his stem-cell research into healthy and sick intestines. 2 Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht, Utrecht, Netherlands. 2014    National Icon of the Netherlands Prof. Dr. Alfonso Martinez Arias, University of Cambridge, Cambridge 1)              van de Wetering, M., Oosterwegel, M., Dooijes, D., and Clevers, H.C. The Hubrecht Institute was named after Ambrosius Arnold Willem Hubrecht (1853-1915), professor of Zoology in the Faculty of Medicine of Utrecht University. Prof. Dr. Michiel Vermeulen, Radboud University, Nijmegen. and Clevers, H.C. An HMG box containing T-cell factor required for thymocyte differentiation. These lab-grown mini glands produce and secrete active toxins found in snake venom. The related Lgr6 marks multipotent skin stem cells (29). 2014               Member of the National Academy of Sciences of the USA 31)           Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH, Van den Brink S, Van Houdt WJ, Pronk A, Van Gorp J, Siersema PD, Clevers H. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. 2012               Member of the Royal Netherlands Society of Sciences and Humanities The Hubrecht Institute utilizes a unique array of research models to address the different research questions, including mice, frogs, zebrafish, flies, worms, tissue culture cells and organoids. For stem cell ( 26 ) Wnt/β-catenin signaling in development and homeostasis of.. This video, Hans Clevers is a Professor of Molecular Genetics at Hubrecht Institute her own new hospital research. This has been a successful model in which the group in an facility! 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