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Hans Clevers

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This article is about a Dutch molecular genetics and stem cell researcher. For the purported horse mathematician, see Clever Hans.

Hans Clevers
Clevers in 2018
Born
Johannes Carolus Clevers[2]

(1957-03-27) 27 March 1957 (age 67)[3][4][5]
Eindhoven, Netherlands[3][4]
NationalityDutch
Alma materUtrecht University
Known forOrganoid generation and application
SpouseEefke Petersen[6]
Children2[3]
AwardsLouis-Jeantet Prize for Medicine
Breakthrough Prize in Life Sciences
Dr A. H. Heineken Prize for Medicine
Körber European Science Prize
Scientific career
FieldsMolecular genetics
Cell biology
InstitutionsRoche
Princess Máxima Center [nl]
University Medical Center Utrecht
Hubrecht Institute for Developmental Biology and Stem Cell Research
Utrecht University
Dana–Farber Cancer Institute
ThesisEarly events in lymphocyte activation (1985)
Doctoral advisorRudy Ballieux[1]

Johannes (Hans) Carolus Clevers (born 27 March 1957)[3][4] is a Dutch molecular geneticist, cell biologist and stem cell researcher. He became the Head of Pharma, Research and Early Development, and a member of the Corporate Executive Committee, of the Swiss healthcare company Roche in 2022.[7][8] Previously, he headed a research group at the Hubrecht Institute for Developmental Biology and Stem Cell Research[9] and at the Princess Máxima Center [nl];[10] he remained as an advisor and guest scientist or visiting researcher to both groups.[7] He is also a Professor in Molecular Genetics at Utrecht University.[8]

Early life and education

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Hans Clevers was born in Eindhoven, the Netherlands in 1957.[5] He began studying biology at Utrecht University in 1975, but also started taking medicine in 1978,[7] in part due to his interest and in part because his friends and brothers were in the medical profession.[11] He spent 1 year in Nairobi, Kenya, and half a year at the National Institutes of Health in Bethesda, United States, for biology rotations.[11][12] He received a Doctoraal (equivalent to an MSc) in Biology in 1982 and an Artsexamen (equivalent to an MD) in 1984. Mostly because of his research background, Clevers was selected for a training position in paediatrics, and then went to pursue a PhD in 1985, under the supervision of Rudy Ballieux.[1][13][14] He obtained his PhD 1 year later.[7][11]

Scholia has a profile for Hans Clevers (Q1579050).
Wikimedia Commons has media related to Hans Clevers.

Career

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After his PhD, Clevers went to the Dana–Farber Cancer Institute as a postdoctoral researcher at Cox Terhorst's group.[8][11][15][16] In 1989, he returned to the Netherlands, joining his alma mater, Utrecht University, as an assistant professor at the Department of Clinical Immunology.[8]

In 1991, Clevers became a professor and the chair of the Department of Immunology at Utrecht University.[8] He moved to the University Medical Center Utrecht in 2002 as a professor in molecular genetics, and started his lab at the Hubrecht Institute for Developmental Biology and Stem Cell Research (Hubrecht Institute).[7] At the same time, he took up the position of Director of the Hubrecht Institute.[8]

In March 2012, Clevers was elected the president of the Royal Netherlands Academy of Arts and Sciences, succeeding Robbert Dijkgraaf.[17][18] His term concluded in 2015, and he started another lab at the Princess Máxima Center [nl],[8] focusing on childhood cancer,[10] and became the Director Research and Chief Scientific Officer there until 2019.[8]

Clevers left University Medical Center Utrecht and was appointed Professor in Molecular Genetics at Utrecht University in 2020.[7]

In 2022, Clevers joined the Swiss healthcare company Roche as its Head of Pharma, Research and Early Development and a member of its Corporate Executive Committee.[19][20] He remains an advisor and guest scientist or visiting researcher to his research groups at the Princess Máxima Center and Hubrecht Institute.[9][10]

Since 2017, Clevers is an investigator at the Oncode Institute in Utrecht.[7][21]

Clevers has served at a number of scientific organizations, including on the board of directors of the American Association for Cancer Research (2013-2016),[22] and the Scientific Advisory Board of the Swiss Institute for Experimental Cancer Research at the École Polytechnique Fédérale de Lausanne (2005-2015),[8] the Research Institute of Molecular Pathology in Vienna (2015-2021)[23] and the Francis Crick Institute in London.[24] He is currently on the advisory board of various scientific journals, including The EMBO Journal,[25] Disease Models & Mechanisms,[26] Cell,[27] Cell Stem Cell[28] and EMBO Molecular Medicine.[29] From 2014 to 2022, he was also on the editorial committee of the Annual Review of Cancer Biology.[7]

Outside the academia, Clevers has been a scientific advisor to numerous biotechnology companies.[7] He also co-founded California-based Surrozen[30] in 2016[31] and Shanghai-based D1 Medical Technology[32] in 2019.[33]

Hans Clevers interviewed for the Dutch television show The Mind of the Universe

Research

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Clevers's early career focused on the Wnt signaling pathway.[34] His group identified the TCF1 protein, a member of the TCF gene family and a crucial downstream component of the Wnt signaling pathway, making it central in immune responses, embryonic development and tissue repair.[35] His interest in the gastrointestinal tract began with the discovery that another TCF family member, the TCF4 protein, is required in forming intestinal crypts.[36] Collaborating with Bert Vogelstein, he found that in colon cancer where the APC gene is doubly mutated, TCF family members activate catenin beta-1, which then enhances the expression of many genes that cause cancer transformation,[37] connecting the Wnt signaling pathway with colon cancer.

In 2007, Clevers's group identified a marker for stem cells of the small and large intestines, LGR5, itself also a target of the Wnt signaling pathway.[38] This led to his finding that LGR5 is a stem cell marker in other organs as well, including the stomach[39] and hair follicles.[40]

Building on this discovery, in 2009, his group published a landmark paper, describing for the first time how organoids, which are 3-dimensional in vitro structures that behave anatomically and molecularly like the organ from which they are derived, were generated from adult stem cells, creating organoids of the small intestine.[41] Clevers's group has applied this technology to culturing organoids from other organs, such as the stomach[39] and liver,[42] as well as from various cancer types, including cancer of the breast[43] and the ovaries.[44] This platform has since been applied in personalized medicine, by generating organoids from specific patients to screen for drugs.[45][46] This is not limited to cancer but is applicable to other diseases as well (for example, cystic fibrosis).[47] His current major research interest is in using organoids derived from adult stem cells to study the molecular mechanism of tissue and cancer development.

During the COVID-19 pandemic, Clevers's group modelled the infection of SARS-CoV-2 using lung organoids.[48]

Honours and awards

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References

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  1. ^ a b "Mentoring the Next Generation: Hans Clevers". Cell Stem Cell. 23 (6): 784–786. 2018. doi:10.1016/j.stem.2018.11.004. S2CID 239579550.
  2. ^ a b "Johannes Carolus Clevers". American Academy of Arts and Sciences. Archived from the original on 27 June 2022.
  3. ^ a b c d "2016 – Johannes C. Clevers". Ilse & Helmut Wachter Foundation, Medical University of Innsbruck. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  4. ^ a b c "Prof.dr. J.C. Clevers" (in Dutch). Utrecht University. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  5. ^ a b "Prof. dr. J.C. (Hans) Clevers" (in Dutch). University Medical Center Utrecht. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  6. ^ Clevers, Hans (1 October 2021). "The development of organoids for cancer research: an ode to the scientific method". Cancer World. Archived from the original on 29 June 2022. Retrieved 29 June 2022.
  7. ^ a b c d e f g h i j "CURRICULUM VITAE" (PDF). Utrecht University. Archived from the original (PDF) on 23 June 2022. Retrieved 23 June 2022.
  8. ^ a b c d e f g h i "Prof. Dr. Hans Clevers". Roche. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  9. ^ a b "Clevers: Adult stem cell-based organoids". Utrecht University. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  10. ^ a b c "Clevers group". Princess Máxima Center [nl]. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  11. ^ a b c d Clevers, H. (2013). "A gutsy approach to stem cells and signalling: an interview with Hans Clevers". Disease Models & Mechanisms. 6 (5): 1053–1056. doi:10.1242/dmm.013367. PMC 3759325. PMID 24046385. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  12. ^ "Hans Clevers on Becoming a Scientist". Cold Spring Harbor Laboratory. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  13. ^ Menkhorst, Roos (22 June 2013). "Ik leerde het belang van vertrouwen in mezelf". Trouw (in Dutch). Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  14. ^ "Hans Clevers". Breakthrough Prize in Life Sciences. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  15. ^ "Hans Clevers". Hubrecht Institute for Developmental Biology and Stem Cell Research. Archived from the original on 31 December 2011. Retrieved 15 March 2012.
  16. ^ "Distinguished Lecture: Hans Clevers - "Gut Stem Cells, Organoids, and Precision Medicine". Columbia University. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  17. ^ van Aartsen, Carina (26 March 2012). "Hans Clevers volgt KNAW-president Robbert Dijkgraaf op". Zorgvisie (in Dutch). Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  18. ^ "President: Hans Clevers". Royal Netherlands Academy of Arts and Sciences. Archived from the original on 1 February 2013.
  19. ^ "New challenge for Hans Clevers at Roche". Hubrecht Institute for Developmental Biology and Stem Cell Research. 1 February 2022. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  20. ^ "Changes to the Roche Board of Directors and the Corporate Executive Committee" (Press release). Basel: Roche. 1 February 2022. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  21. ^ "Hans Clevers Group". Oncode Institute. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  22. ^ "American Association for Cancer Research Councilors and Directors" (PDF). American Association for Cancer Research. Archived from the original (PDF) on 24 June 2022. Retrieved 24 June 2022.
  23. ^ "Former SAB Members". Research Institute of Molecular Pathology. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  24. ^ "Hans Clevers". Francis Crick Institute. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  25. ^ "Advisory Board Biographies". The EMBO Journal. Archived from the original on 27 June 2022. Retrieved 24 June 2022.
  26. ^ "Editors and Board". Disease Models & Mechanisms. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  27. ^ "Staff and advisory board". Cell. Archived from the original on 27 June 2022. Retrieved 24 June 2022.
  28. ^ "Advisory board". Cell Stem Cell. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  29. ^ "Advisory Board Biographies". EMBO Molecular Medicine. Archived from the original on 27 June 2022. Retrieved 24 June 2022.
  30. ^ "Hans Clevers, MD, PhD". Surrozen. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  31. ^ "Surrozen to Present at Cowen and Company 40th Annual Health Care Conference". Surrozen (Press release). South San Francisco, California. 2 March 2020. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  32. ^ "创始团队" (in Chinese). D1 Medical Technology. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  33. ^ "丹望医疗完成数千万元天使轮融资，凯风创投领投". Sina (in Chinese). 8 February 2021. Archived from the original on 24 June 2022. Retrieved 24 June 2022.
  34. ^ Sinha, Gunjan (2017). "The organoid architect". Science. 357 (6353): 746–749. doi:10.1126/science.357.6353.746. PMID 28839056. Archived from the original on 28 June 2022. Retrieved 28 June 2022.
  35. ^ van de Wetering, Marc; Oosterwegel, Mariette; Dooijes, Dennis; Clevers, Hans (1991). "Identification and cloning of TCF-1, a T cell-specific transcription factor containing a sequence-specific HMG box". The EMBO Journal. 10 (1): 123–132. doi:10.1002/j.1460-2075.1991.tb07928.x. PMC 452620. PMID 1989880.
  36. ^ Korinek, Vladimir; Barker, Nick; Moerer, Petra; van Donselaar, Elly; Huls, Gerwin; Peters, Peter J.; Clevers, Hans (1997). "Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4". Nature Genetics. 19 (4): 379–383. doi:10.1038/1270. PMID 9697701. S2CID 1052683. Retrieved 28 June 2022.
  37. ^ Korinek, Vladimir; Barker, Nick; Morin, Patrice J.; van Wichen, Dick; de Weger, Roel; Kinzler, Kenneth W.; Vogelstein, Bert; Clevers, Hans (1997). "Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC−/− Colon Carcinoma". Science. 275 (5307): 1784–1787. doi:10.1126/science.275.5307.1784. PMID 9065401. S2CID 33935423. Retrieved 28 June 2022.
  38. ^ Barker, Nick; van Es, Johan H.; Kuipers, Jeroen; Kujala, Pekka; van den Born, Maaike; Cozijnsen, Miranda; Haegebarth, Andrea; Korving, Jeroen; Begthel, Harry; Peters, Peter J.; Clevers, Hans (2007). "Identification of stem cells in small intestine and colon by marker gene Lgr5". Nature. 449 (7165): 1003–1007. Bibcode:2007Natur.449.1003B. doi:10.1038/nature06196. PMID 17934449. S2CID 4349637. Retrieved 23 June 2022.
  39. ^ a b Barker, Nick; Huch, Meritxell; Kujala, Pekka; van de Wetering, Marc; Snippert, Hugo J.; van Es, Johan H.; Sato, Toshiro; Stange, Daniel E.; Begthel, Harry; van den Born, Maaike; Danenberg, Esther; van den Brink, Stieneke; Korving, Jeroen; Abo, Arie; Peters, Peter J.; Wright, Nick; Poulsom, Richard; Clevers, Hans (2010). "Lgr5+ve Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro". Cell Stem Cell. 6 (1): 25–36. doi:10.1016/j.stem.2009.11.013. PMID 20085740.
  40. ^ Jaks, Viljar; Barker, Nick; Kasper, Maria; van Es, Johan H; Snippert, Hugo J; Clevers, Hans; Toftgård, Rune (2008). "Lgr5 marks cycling, yet long-lived, hair follicle stem cells". Nature Genetics. 40 (11): 1291–1299. doi:10.1038/ng.239. PMID 18849992. S2CID 10883817. Retrieved 23 June 2022.
  41. ^ Sato, Toshiro; Vries, Robert G.; Snippert, Hugo J.; van de Wetering, Marc; Barker, Nick; Stange, Daniel E.; van Es, Johan H.; Abo, Arie; Kujala, Pekka; Peters, Peter J.; Clevers, Hans (2009). "Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche". Nature. 459 (7244): 262–265. Bibcode:2009Natur.459..262S. doi:10.1038/nature07935. PMID 19329995. S2CID 4373784. Retrieved 23 June 2022.
  42. ^ Huch, Meritxell; Dorrell, Craig; Boj, Sylvia F.; van Es, Johan H.; van de Wetering, Marc; Li, Vivian S.W.; Hamer, Karien; Sasaki, Nobuo; Finegold, Milton J.; Haft, Annelise; Grompe, Markus; Clevers, Hans (2013). "In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration". Nature. 494 (7436): 247–250. Bibcode:2013Natur.494..247H. doi:10.1038/nature11826. PMC 3634804. PMID 23354049.
  43. ^ Sachs, Norman; de Ligt, Joep; Kopper, Oded; Gogola, Ewa; Bounova, Gergana; Weeber, Fleur; Vanita Balgobind, Anjali; Wind, Karin; Gracanin, Ana; Begthel, Harry; Korving, Jeroen; van Boxtel, Ruben; Alves Duarte, Alexandra; Lelieveld, Daphne; van Hoeck, Arne; Ernst, Robert Frans; Blokzijl, Francis; Nijman, Isaac Johannes; Hoogstraat, Marlous; van de Ven, Marieke; Egan, David Anthony; Zinzalla, Vittoria; Moll, Jurgen; Fernandez Boj, Sylvia; Voest, Emile Eugene; Wessels, Lodewyk; van Diest, Paul Joannes; Rottenberg, Sven; Vries, Robert Gerhardus Jacob; Cuppen, Edwin; Clevers, Hans (2018). "A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity". Cell. 172 (1–2): 373–386. doi:10.1016/j.cell.2017.11.010. PMID 29224780. S2CID 8951522.
  44. ^ Kopper, Oded; de Witte, Chris J.; Lõhmussaar, Kadi; Valle-Inclan, Jose Espejo; Hami, Nizar; Kester, Lennart; Vanita Balgobind, Anjali; Korving, Jeroen; Proost, Natalie; Begthel, Harry; van Wijk, Lise M; Aristín Revilla, Sonia; Theeuwsen, Rebecca; van de Ven, Marieke; van Roosmalen, Markus J; Ponsioen, Bas; Ho, Victor W. H.; Neel, Benjamin G.; Bosse, Tjalling; Gaarenstroom, Katja N.; Vrieling, Harry; Vreeswijk, Maaike P. G.; van Diest, Paul J.; Witteveen, Petronella O.; Jonges, Trudy; Bos, Johannes L.; van Oudenaarden, Alexander; Zweemer, Ronald P.; Snippert, Hugo J. G.; Kloosterman 14, Hans Clevers, Wigard P. (2019). "An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity". Nature Medicine. 25 (5): 838–849. doi:10.1038/s41591-019-0422-6. PMID 31011202. S2CID 126428230. Retrieved 29 June 2022.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  45. ^ Bartfeld, Sina (2021). "Realizing the potential of organoids—an interview with Hans Clevers". Journal of Molecular Medicine. 99 (4): 443–447. doi:10.1007/s00109-020-02025-3. PMC 8026466. PMID 33464358.
  46. ^ Bender, Eric (2015). "Q&A: Hans Clevers". Nature. 521 (7551): S15. Bibcode:2015Natur.521S..15B. doi:10.1038/521S15a. PMID 25970453. S2CID 4452738.
  47. ^ Saini, Angela (2016). "Cystic Fibrosis Patients Benefit from Mini Guts" (PDF). Cell Stem Cell. 19 (4): 425–427. doi:10.1016/j.stem.2016.09.001. Archived from the original (PDF) on 25 June 2022. Retrieved 26 June 2022.
  48. ^ Lamers, Mart M; van der Vaart, Jelte; Knoops, Kèvin; Riesebosch, Samra; Breugem, Tim I; Mykytyn, Anna Z; Beumer, Joep; Schipper, Debby; Bezstarosti, Karel; Koopman, Charlotte D; Groen, Nathalie; Ravelli, Raimond B G; Duimel, Hans Q; Demmers, Jeroen A A; Verjans, Georges M G M; Koopmans, Marion P G; Muraro, Mauro J; Peters, Peter J; Clevers, Hans; Haagmans, Bart L (2021). "An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells". The EMBO Journal. 40 (5): e105912. doi:10.15252/embj.2020105912. PMC 7883112. PMID 33283287.
  49. ^ "Hans C. Clevers". European Molecular Biology Organization. Archived from the original on 26 June 2022. Retrieved 26 June 2022.
  50. ^ "Hans Clevers". Royal Netherlands Academy of Arts and Sciences. Archived from the original on 16 August 2019. Retrieved 16 August 2019.
  51. ^ "NWO Spinoza Prize 2001". Dutch Research Council. Archived from the original on 31 October 2020. Retrieved 31 October 2020.
  52. ^ "Professor Hans CLEVERS". Louis-Jeantet Foundation. October 2017. Archived from the original on 26 June 2022. Retrieved 26 June 2022.
  53. ^ "Die Preisträger" (in German). Meyenburg Foundation. 30 April 2005. Archived from the original on 4 April 2022. Retrieved 26 June 2022.
  54. ^ "Hans Clevers". Academia Europaea. Archived from the original on 26 June 2022. Retrieved 26 June 2022.
  55. ^ "Awards & Grants : UEGF Research Prize : EUR 100.000 awarded for the most outstanding research programme". UEGW Barcelona 2010 : 18th United European Gastroenterology Week : Final Programme. United European Gastroenterology Federation (UEGF). 2010. p. 20. Archived from the original on 6 January 2024. Retrieved 6 January 2024.
  56. ^ "Laureates 1976 to 2021". Ernst Jung Foundation. Archived from the original on 27 June 2022. Retrieved 27 June 2022.
  57. ^ "William Beaumont Prize in Gastroenterology". American Gastroenterological Association. Archived from the original on 27 June 2022. Retrieved 27 June 2022.
  58. ^ "Hans Clevers". Heineken Prizes. Archived from the original on 27 June 2022. Retrieved 27 June 2022.
  59. ^ "Koninklijke onderscheidingen 2012" (in Dutch). Utrecht University. Archived from the original on 9 May 2015. Retrieved 9 May 2015.
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  62. ^ "Hans Clevers". National Academy of Sciences. Archived from the original on 27 June 2022. Retrieved 27 June 2022.
  63. ^ "Hans Clevers, MD, PhD". American Association for Cancer Research. Archived from the original on 27 June 2022. Retrieved 27 June 2022.
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  67. ^ "Hans Clevers (2016): Replacement organs from a petri dish". Körber Foundation. Archived from the original on 27 June 2022. Retrieved 27 June 2022.
  68. ^ "German award for Hans Clevers". Princess Máxima Center. 2 March 2018. Archived from the original on 27 June 2022. Retrieved 27 June 2022.
  69. ^ "Hans Clevers". Royal Society. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
  70. ^ "Professor Johannes Carolus Clevers ForMemRS, HonFRSE". Royal Society of Edinburgh. Archived from the original on 1 August 2020. Retrieved 1 August 2020.
  71. ^ "Hans C. Clevers" (in Japanese). Keio University. Archived from the original on 15 May 2020. Retrieved 27 June 2022.
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