h.clevers@hubrecht.eu. In 1916, after Hubrecht’s death, the first Hubrecht Laboratory was established in Hubrecht’s residence at Janskerkhof. Cell 161: 933-945 (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., Clevers, H. Sequential cancer mutations in cultured human intestinal stem cells. 2013 – 2015      Canada Gairdner Award, Toronto The Institute is very strong in developing new methods and transferring this knowledge to institutes and universities in the Netherlands and beyond. 2014    TEFAF Oncology Chair 2014, Maastricht 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. 2011    The Ernst Jung Medical Award, Germany 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. Here, several important advances in developmental biology were made, including the pioneering work of Pieter Nieuwkoop, after whom the area of an embryo called the “Nieuwkoop center” is named. 1991 – 2002      Professor and Chairman, Dept. 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. 2014    Fellow of the AACR Academy 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). Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. Science 307: 1904-1909 (2005), 19)           Reya, T., Clevers, H., Wnt signalling in stem cells and cancer. This is reflected by a citation impact score of around 3.0, putting the Hubrecht at the top of the list of all institutes and universities in the Netherlands. 2020 – present  Member of the Board of Genentech, South San Francisco From Utrecht Central Station, it takes only 30 min to get to Amsterdam airport, Schiphol, an international hub for most major airlines. 2005    The Science and Society Prize, Amsterdam Stem cells and organoids Hans Clevers became famous with his stem-cell research into healthy and sick intestines. He also serves as Director of the Princess Maxima Center for Pediatric Oncology. Celebrating 100 years of Developmental Biology at the Hubrecht Institute European Molecular Biology Laboratory (EMBL) In 2000 the Hubrecht moved into a new, larger building built alongside the old building to accommodate the growing number of research groups. 2019               Foreign Member of the Royal Society, London, United Kingdom 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. 10 Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. At the beginning of the 1880s Hubrecht corresponded with Charles Darwin, who paved the way for the theory of evolution in his book “On the origin of species”. About Us. 2016    The Ilse & Helmut Wachter award, Hamburg, Germany 1985 – 1989      Postdoctoral Fellow, Cox Terhorst Lab at the Dana-Farber Cancer Institute, Boston MA, USA 3584 CT Utrecht Oncode Institute 3 Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. 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., Clevers, H. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. UMC Utrecht Marie-José Goumans. 2012 – 2015      Member of the Board of the American Association of Cancer Research Find 152 researchers working at Hubrecht Institute | Utrecht, Netherlands | Prof. Dr. Alfonso Martinez Arias, University of Cambridge, Cambridge Amongst the Wnt target genes, we found the Lgr5 gene to be unique in that it marks small cycling cells at crypt bottoms. 2012               Member of the Royal Netherlands Society of Sciences and Humanities Marie-José Goumans: Cultured heart cells. Lgr5 resides in Wnt receptor complexes and mediates signaling of the R-spondin Wnt agonists (33), explaining the unique dependence of Lgr5 stem cells of various epithelia on R-spondins in vivo and in vitro. 2012    Knight in the Order of the Netherlands’ Lion The tumor suppressor protein APC forms the core of a cytoplasmic complex which binds ß-catenin and targets it for degradation in the proteasome. 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. and Clevers, H. Visualization of the short-range Wnt gradient in the intestinal stem cell niche. Currently, four private partners distribute technologies developed at the Hubrecht Institute. It promotes quality in science and scholarship and strives to ensure that Dutch scholars and scientists contribute to cultural, social and economic progress. 2019 – present  Honorary Director, Fudan Organoid Center, Fudan University, Shanghai 220 were here. Royal Netherlands Academy of Arts and Sciences (KNAW) Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Clevers Group. Stem cells and organoids Hans Clevers became famous with his stem-cell research into healthy and sick intestines. 2002 – 2012      Director Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences The scientific advisory board of the Hubrecht Institute meets once a year and is involved in the tenure track evaluations of the junior PI’s. The Wnt target gene encoding the transcription factor Achaete scute-like 2 controls the fate of the intestinal stem cell (26). ↵ ‡ To whom correspondence should be addressed. The Hubrecht Institute was named after Ambrosius Arnold Willem Hubrecht (1853-1915), professor of Zoology in the Faculty of Medicine of Utrecht University. Gijs van den Brink: Tackling chronic inflammatory bowel disease. 2015                     Pezcoller Foundation – AACR International Award for Cancer Research, Italy The board of directors, consisting of Prof. Alexander van Oudenaarden (director) and Prof. Jeroen den Hertog (managing director) maintains a flat organizational structure with tenure track positions for junior group leaders. The Hubrecht Institute has a partnership with the European Molecular Biology Laboratory (EMBL) based on shared institutional goals, scientific synergy and complementarity. 2015 – present  Visiting professor, University of Melbourne, Australia h.clevers@hubrecht.eu. Electronic address: h.clevers@hubrecht.eu. 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. For these studies, we designed the widely used pTOPFLASH Wnt reporters. 2006 – 2008      President of the International Society of Differentiation (ISD) A center for interdisciplinary biomedical research. 2014 – present  Breakthrough Prize in Life Sciences, San Francisco 2016    Swammerdam medal, Amsterdam and Clevers, H. Intestinal Crypt Homeostasis results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells. Since 2008, the Hubrecht is … Stem cells numbers remain fixed because stem cells compete ‘neutrally’  for niche space. Culturing heart tissue. Allele Type Gene Symbol Gene Name; Targeted (Conditional ready (e.g. 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. In this video, Hans Clevers summarizes the use of organdies in cancer research. In 2007 the name was changed from Hubrecht Laboratory to Hubrecht Institute. I am a PhD student in Hans Clevers' lab at the Hubrecht Institute with a strong interest in colorectal cancer immunotherapy and organoids. 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". The Hubrecht Institute collaborates with numerous laboratories, internationally, nationally and locally, always aiming to improve our research. In mammals, physiological Wnt signaling is intimately involved with the biology of adult stem cells and self-renewing tissues (18,19). A springboard for senior group leaders. 2015                     Dr. Paul Janssen Award, Bruxelles 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. 3584 CT Utrecht 2019    Keio Medical Science Prize of the Keio University (Japan) At the start of their PhD, the PhD students draft a Training & Supervision Agreement (TSA) and during their PhD they have yearly meetings with their supervisory committee, which includes 2-3 independent researchers. 1)              van de Wetering, M., Oosterwegel, M., Dooijes, D., and Clevers, H.C. 2 Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht, Utrecht, Netherlands. On the shoulders of Hubrecht: From embryos to stem cells. 11 Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, Utrecht, The Netherlands h.clevers@hubrecht.eu. Stem cell research and developmental biology. 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. Daughters of the small intestinal stem cells, the Paneth cells, serve as crypt niche cells by providing Wnt, Notch and EGF signals (30). Dr. Clevers received his M.D. 2009               Member of the Academia Europaea Cell 160: 299-312 (2015), 47)           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. In a collaboration with the Cystic Fibrosis clinic in Utrecht, a functional assay was established for the CFTR channel using rectal organoids. Oncode includes 62 research groups of the Dutch University Medical Centers, the Hubrecht Institute and the Netherlands Cancer Institute. For example, during the last year more than half of the top publications from the Hubrecht Institute involved more than two Hubrecht groups, demonstrating the collaborative spirit. Technology is transferred to society as efficiently as possible. Hans Clevers is both group leader at the Hubrecht Institute and scientific director of the PMC, ensuring a steady relationship. Maurice, M.M. 1991 – 2002      Professor and Chairman, Dept. A breeding ground for spin off companies. Prof. Dr. Edith Heard, EMBL, Heidelberg Organoid models of human and mouse ductal pancreatic cancer. 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. 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