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| thesis_url = https://utrechtuniversity.on.worldcat.org/oclc/63836041
| thesis_url = https://utrechtuniversity.on.worldcat.org/oclc/63836041
| thesis_year = 1985
| thesis_year = 1985
| doctoral_advisor = [[Rudy Ballieux]]<ref name="cellstemcell">{{cite journal |title=Mentoring the Next Generation: Hans Clevers |journal=[[Cell Stem Cell]] |date=2018 |volume=23 |issue=6 |pages=784–786 |doi=10.1016/j.stem.2018.11.004 |s2cid=239579550 |url=https://www.sciencedirect.com/science/article/pii/S193459091830540X |access-date=23 June 2022 |archive-date=23 June 2022 |archive-url=https://archive.today/20220623030631/https://www.sciencedirect.com/science/article/pii/S193459091830540X|doi-access=free }}</ref>
| doctoral_advisor = [[Rudy Ballieux]]<ref name="cellstemcell">{{cite journal |title=Mentoring the Next Generation: Hans Clevers |journal=[[Cell Stem Cell]] |date=2018 |volume=23 |issue=6 |pages=784–786 |doi=10.1016/j.stem.2018.11.004 |s2cid=239579550 |doi-access=free }}</ref>
| academic_advisors =
| academic_advisors =
| doctoral_students =
| doctoral_students =
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Outside the academia, Clevers has been a scientific advisor to numerous [[biotechnology]] companies.<ref name="cv"/> He also co-founded [[California]]-based Surrozen<ref>{{cite web |title=Hans Clevers, MD, PhD |url=https://www.surrozen.com/team/hans-clevers |publisher=Surrozen |access-date=24 June 2022 |archive-url=https://web.archive.org/web/20220624073719/https://www.surrozen.com/team/hans-clevers |archive-date=24 June 2022}}</ref> in 2016<ref>{{cite press release |title=Surrozen to Present at Cowen and Company 40th Annual Health Care Conference |url=https://www.surrozen.com/press-releases/surrozen-to-present-at-cowen-and-company-40th-annual-health-care-conference |access-date=24 June 2022 |work=Surrozen |date=2 March 2020 |archive-url=https://web.archive.org/web/20220624074629/https://www.surrozen.com/press-releases/surrozen-to-present-at-cowen-and-company-40th-annual-health-care-conference |archive-date=24 June 2022 |location=[[South San Francisco, California]]}}</ref> and [[Shanghai]]-based D1 Medical Technology<ref>{{cite web |title=创始团队 |url=http://www.d1med.com/h-col-111.html |publisher=D1 Medical Technology |access-date=24 June 2022 |archive-url=https://web.archive.org/web/20220624082243/http://www.d1med.com/h-col-111.html |archive-date=24 June 2022 |language=zh}}</ref> in 2019.<ref>{{cite news |title=丹望医疗完成数千万元天使轮融资，凯风创投领投 |url=https://finance.sina.com.cn/tech/2021-02-08/doc-ikftssap4842394.shtml |access-date=24 June 2022 |work=[[Sina Corporation|Sina]] |date=8 February 2021 |archive-url=https://web.archive.org/web/20220624083207/https://finance.sina.com.cn/tech/2021-02-08/doc-ikftssap4842394.shtml |archive-date=24 June 2022 |language=zh}}</ref>
Outside the academia, Clevers has been a scientific advisor to numerous [[biotechnology]] companies.<ref name="cv"/> He also co-founded [[California]]-based Surrozen<ref>{{cite web |title=Hans Clevers, MD, PhD |url=https://www.surrozen.com/team/hans-clevers |publisher=Surrozen |access-date=24 June 2022 |archive-url=https://web.archive.org/web/20220624073719/https://www.surrozen.com/team/hans-clevers |archive-date=24 June 2022}}</ref> in 2016<ref>{{cite press release |title=Surrozen to Present at Cowen and Company 40th Annual Health Care Conference |url=https://www.surrozen.com/press-releases/surrozen-to-present-at-cowen-and-company-40th-annual-health-care-conference |access-date=24 June 2022 |work=Surrozen |date=2 March 2020 |archive-url=https://web.archive.org/web/20220624074629/https://www.surrozen.com/press-releases/surrozen-to-present-at-cowen-and-company-40th-annual-health-care-conference |archive-date=24 June 2022 |location=[[South San Francisco, California]]}}</ref> and [[Shanghai]]-based D1 Medical Technology<ref>{{cite web |title=创始团队 |url=http://www.d1med.com/h-col-111.html |publisher=D1 Medical Technology |access-date=24 June 2022 |archive-url=https://web.archive.org/web/20220624082243/http://www.d1med.com/h-col-111.html |archive-date=24 June 2022 |language=zh}}</ref> in 2019.<ref>{{cite news |title=丹望医疗完成数千万元天使轮融资，凯风创投领投 |url=https://finance.sina.com.cn/tech/2021-02-08/doc-ikftssap4842394.shtml |access-date=24 June 2022 |work=[[Sina Corporation|Sina]] |date=8 February 2021 |archive-url=https://web.archive.org/web/20220624083207/https://finance.sina.com.cn/tech/2021-02-08/doc-ikftssap4842394.shtml |archive-date=24 June 2022 |language=zh}}</ref>


[[File:Chemist Hans Clevers replaces worn-down body parts with organoids created outside the body-VPRO-The Mind of the Universe.ogv|thumb|Hans Clevers interviewed for the Dutch [[television show]] The Mind of the Universe.]]
[[File:Chemist Hans Clevers replaces worn-down body parts with organoids created outside the body-VPRO-The Mind of the Universe.ogv|thumb|Hans Clevers interviewed for the Dutch [[television show]] The Mind of the Universe]]


== Research ==
== Research ==
Clevers's early career focused on the [[Wnt signaling pathway]].<ref>{{cite journal |last1=Sinha |first1=Gunjan |title=The organoid architect |journal=Science |date=2017 |volume=357 |issue=6353 |pages=746–749 |doi=10.1126/science.357.6353.746 |pmid=28839056 |url=https://www.science.org/doi/full/10.1126/science.357.6353.746 |access-date=28 June 2022 |archive-date=28 June 2022 |archive-url=https://archive.today/20220628041747/https://www.science.org/doi/full/10.1126/science.357.6353.746}}</ref> His group identified the [[TCF7|TCF1]] protein, a member of the [[TCF/LEF family|TCF gene family]] and a crucial downstream component of the Wnt signaling pathway, making it central in [[immune response]]s, [[Human embryonic development|embryonic development]] and tissue repair.<ref>{{cite journal |last1=van de Wetering |first1=Marc |last2=Oosterwegel |first2=Mariette |last3=Dooijes |first3=Dennis |last4=Clevers |first4=Hans |title=Identification and cloning of TCF-1, a T cell-specific transcription factor containing a sequence-specific HMG box |journal=The EMBO Journal |date=1991 |volume=10 |issue=1 |pages=123–132 |doi=10.1002/j.1460-2075.1991.tb07928.x |pmid=1989880 |pmc=452620 }}</ref> His interest in the [[gastrointestinal tract]] began with the discovery that another TCF family member, the [[TCF7L2|TCF4]] protein, is required in forming [[Intestinal gland|intestinal crypts]].<ref>{{cite journal |last1=Korinek |first1=Vladimir |last2=Barker |first2=Nick |last3=Moerer |first3=Petra |last4=van Donselaar |first4=Elly |last5=Huls |first5=Gerwin |last6=Peters |first6=Peter J. |last7=Clevers |first7=Hans |title=Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4 |journal=[[Nature Genetics]] |date=1997 |volume=19 |issue=4 |pages=379–383 |doi=10.1038/1270 |pmid=9697701 |s2cid=1052683 |url=https://www.nature.com/articles/ng0898_379 |access-date=28 June 2022 |url-access=subscription}}</ref> Collaborating with [[Bert Vogelstein]], he found that in [[Colorectal cancer|colon cancer]] where the [[Adenomatous polyposis coli|APC]] gene is doubly mutated, TCF family members activate [[catenin beta-1]], which then enhances the expression of many genes that cause [[Carcinogenesis|cancer transformation]],<ref>{{cite journal |last1=Korinek |first1=Vladimir |last2=Barker |first2=Nick |last3=Morin |first3=Patrice J. |last4=van Wichen |first4=Dick |last5=de Weger |first5=Roel |last6=Kinzler |first6=Kenneth W. |last7=Vogelstein |first7=Bert |last8=Clevers |first8=Hans |title=Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC<sup>−/−</sup> Colon Carcinoma |journal=[[Science (journal)|Science]] |date=1997 |volume=275 |issue=5307 |pages=1784–1787 |doi=10.1126/science.275.5307.1784 |pmid=9065401 |s2cid=33935423 |url=https://www.science.org/doi/10.1126/science.275.5307.1784 |access-date=28 June 2022 |url-access=subscription}}</ref> connecting the Wnt signaling pathway with colon cancer.
Clevers's early career focused on the [[Wnt signaling pathway]].<ref>{{cite journal |last1=Sinha |first1=Gunjan |title=The organoid architect |journal=Science |date=2017 |volume=357 |issue=6353 |pages=746–749 |doi=10.1126/science.357.6353.746 |pmid=28839056 |url=https://www.science.org/doi/full/10.1126/science.357.6353.746 |access-date=28 June 2022 |archive-date=28 June 2022 |archive-url=https://archive.today/20220628041747/https://www.science.org/doi/full/10.1126/science.357.6353.746}}</ref> His group identified the [[TCF7|TCF1]] protein, a member of the [[TCF/LEF family|TCF gene family]] and a crucial downstream component of the Wnt signaling pathway, making it central in [[immune response]]s, [[Human embryonic development|embryonic development]] and tissue repair.<ref>{{cite journal |last1=van de Wetering |first1=Marc |last2=Oosterwegel |first2=Mariette |last3=Dooijes |first3=Dennis |last4=Clevers |first4=Hans |title=Identification and cloning of TCF-1, a T cell-specific transcription factor containing a sequence-specific HMG box |journal=The EMBO Journal |date=1991 |volume=10 |issue=1 |pages=123–132 |doi=10.1002/j.1460-2075.1991.tb07928.x |pmid=1989880 |pmc=452620 }}</ref> His interest in the [[gastrointestinal tract]] began with the discovery that another TCF family member, the [[TCF7L2|TCF4]] protein, is required in forming [[Intestinal gland|intestinal crypts]].<ref>{{cite journal |last1=Korinek |first1=Vladimir |last2=Barker |first2=Nick |last3=Moerer |first3=Petra |last4=van Donselaar |first4=Elly |last5=Huls |first5=Gerwin |last6=Peters |first6=Peter J. |last7=Clevers |first7=Hans |title=Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4 |journal=[[Nature Genetics]] |date=1997 |volume=19 |issue=4 |pages=379–383 |doi=10.1038/1270 |pmid=9697701 |s2cid=1052683 |url=https://www.nature.com/articles/ng0898_379 |access-date=28 June 2022 |url-access=subscription}}</ref> Collaborating with [[Bert Vogelstein]], he found that in [[Colorectal cancer|colon cancer]] where the [[Adenomatous polyposis coli|APC]] gene is doubly mutated, TCF family members activate [[catenin beta-1]], which then enhances the expression of many genes that cause [[Carcinogenesis|cancer transformation]],<ref>{{cite journal |last1=Korinek |first1=Vladimir |last2=Barker |first2=Nick |last3=Morin |first3=Patrice J. |last4=van Wichen |first4=Dick |last5=de Weger |first5=Roel |last6=Kinzler |first6=Kenneth W. |last7=Vogelstein |first7=Bert |last8=Clevers |first8=Hans |title=Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC<sup>−/−</sup> Colon Carcinoma |journal=[[Science (journal)|Science]] |date=1997 |volume=275 |issue=5307 |pages=1784–1787 |doi=10.1126/science.275.5307.1784 |pmid=9065401 |s2cid=33935423 |url=https://www.science.org/doi/10.1126/science.275.5307.1784 |access-date=28 June 2022 |url-access=subscription}}</ref> connecting the Wnt signaling pathway with colon cancer.


In 2007, Clevers's group identified a marker for [[stem cell]]s of the [[Small intestine|small]] and [[large intestine]]s, [[LGR5]], itself also a target of the Wnt signaling pathway.<ref>{{cite journal |last1=Barker |first1=Nick |last2=van Es |first2=Johan H. |last3=Kuipers |first3=Jeroen |last4=Kujala |first4=Pekka |last5=van den Born |first5=Maaike |last6=Cozijnsen |first6=Miranda |last7=Haegebarth |first7=Andrea |last8=Korving |first8=Jeroen |last9=Begthel |first9=Harry |last10=Peters |first10=Peter J. |last11=Clevers |first11=Hans |title=Identification of stem cells in small intestine and colon by marker gene Lgr5 |journal=[[Nature (journal)|Nature]] |date=2007 |volume=449 |issue=7165 |pages=1003–1007 |doi=10.1038/nature06196 |pmid=17934449 |bibcode=2007Natur.449.1003B |s2cid=4349637 |url=https://www.nature.com/articles/nature06196 |access-date=23 June 2022 |url-access=subscription}}</ref> This led to his finding that LGR5 is a stem cell marker in other [[Organ (biology)|organs]] as well, including the [[stomach]]<ref name="stomachorganoid">{{cite journal |first1=Nick |last1=Barker |first2=Meritxell |last2=Huch |first3=Pekka |last3=Kujala |first4=Marc |last4=van de Wetering |first5=Hugo J. |last5=Snippert |first6=Johan H. |last6=van Es |first7=Toshiro |last7=Sato |first8=Daniel E. |last8=Stange |first9=Harry |last9=Begthel |first10=Maaike |last10=van den Born |first11=Esther |last11=Danenberg |first12=Stieneke |last12=van den Brink |first13=Jeroen |last13=Korving |first14=Arie |last14=Abo |first15=Peter J. |last15=Peters |first16=Nick |last16=Wright |first17=Richard |last17=Poulsom |first18=Hans |last18=Clevers |title=Lgr5<sup>+ve</sup> Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro |journal=Cell Stem Cell |date=2010 |volume=6 |issue=1 |pages=25–36 |doi=10.1016/j.stem.2009.11.013 |pmid=20085740 |url=https://www.sciencedirect.com/science/article/pii/S1934590909006183 |access-date=29 June 2022 |archive-date=29 June 2022 |archive-url=https://archive.today/20220629033911/https://www.sciencedirect.com/science/article/pii/S1934590909006183|doi-access=free }}</ref> and [[hair follicle]]s.<ref>{{cite journal |last1=Jaks |first1=Viljar |last2=Barker |first2=Nick |last3=Kasper |first3=Maria |last4=van Es |first4=Johan H |last5=Snippert |first5=Hugo J |last6=Clevers |first6=Hans |last7=Toftgård |first7=Rune |title=Lgr5 marks cycling, yet long-lived, hair follicle stem cells |journal=Nature Genetics |date=2008 |volume=40 |issue=11 |pages=1291–1299 |doi=10.1038/ng.239 |pmid=18849992 |s2cid=10883817 |access-date=23 June 2022 |url=https://www.nature.com/articles/ng.239 |url-access=subscription}}</ref>
In 2007, Clevers's group identified a marker for [[stem cell]]s of the [[Small intestine|small]] and [[large intestine]]s, [[LGR5]], itself also a target of the Wnt signaling pathway.<ref>{{cite journal |last1=Barker |first1=Nick |last2=van Es |first2=Johan H. |last3=Kuipers |first3=Jeroen |last4=Kujala |first4=Pekka |last5=van den Born |first5=Maaike |last6=Cozijnsen |first6=Miranda |last7=Haegebarth |first7=Andrea |last8=Korving |first8=Jeroen |last9=Begthel |first9=Harry |last10=Peters |first10=Peter J. |last11=Clevers |first11=Hans |title=Identification of stem cells in small intestine and colon by marker gene Lgr5 |journal=[[Nature (journal)|Nature]] |date=2007 |volume=449 |issue=7165 |pages=1003–1007 |doi=10.1038/nature06196 |pmid=17934449 |bibcode=2007Natur.449.1003B |s2cid=4349637 |url=https://www.nature.com/articles/nature06196 |access-date=23 June 2022 |url-access=subscription}}</ref> This led to his finding that LGR5 is a stem cell marker in other [[Organ (biology)|organs]] as well, including the [[stomach]]<ref name="stomachorganoid">{{cite journal |first1=Nick |last1=Barker |first2=Meritxell |last2=Huch |first3=Pekka |last3=Kujala |first4=Marc |last4=van de Wetering |first5=Hugo J. |last5=Snippert |first6=Johan H. |last6=van Es |first7=Toshiro |last7=Sato |first8=Daniel E. |last8=Stange |first9=Harry |last9=Begthel |first10=Maaike |last10=van den Born |first11=Esther |last11=Danenberg |first12=Stieneke |last12=van den Brink |first13=Jeroen |last13=Korving |first14=Arie |last14=Abo |first15=Peter J. |last15=Peters |first16=Nick |last16=Wright |first17=Richard |last17=Poulsom |first18=Hans |last18=Clevers |title=Lgr5<sup>+ve</sup> Stem Cells Drive Self-Renewal in the Stomach and Build Long-Lived Gastric Units In Vitro |journal=Cell Stem Cell |date=2010 |volume=6 |issue=1 |pages=25–36 |doi=10.1016/j.stem.2009.11.013 |pmid=20085740 |doi-access=free }}</ref> and [[hair follicle]]s.<ref>{{cite journal |last1=Jaks |first1=Viljar |last2=Barker |first2=Nick |last3=Kasper |first3=Maria |last4=van Es |first4=Johan H |last5=Snippert |first5=Hugo J |last6=Clevers |first6=Hans |last7=Toftgård |first7=Rune |title=Lgr5 marks cycling, yet long-lived, hair follicle stem cells |journal=Nature Genetics |date=2008 |volume=40 |issue=11 |pages=1291–1299 |doi=10.1038/ng.239 |pmid=18849992 |s2cid=10883817 |access-date=23 June 2022 |url=https://www.nature.com/articles/ng.239 |url-access=subscription}}</ref>


Building on this discovery, in 2009, his group published a landmark paper, describing for the first time how [[organoid]]s, which are [[Three-dimensional space|3-dimensional]] ''[[in vitro]]'' structures that behave [[Anatomy|anatomically]] and [[Molecular biology|molecularly]] like the organ from which they are derived, were generated from [[adult stem cell]]s, creating organoids of the [[small intestine]].<ref>{{cite journal |last1=Sato |first1=Toshiro |last2=Vries |first2=Robert G. |last3=Snippert |first3=Hugo J. |last4=van de Wetering |first4=Marc |last5=Barker |first5=Nick |last6=Stange |first6=Daniel E. |last7=van Es |first7=Johan H. |last8=Abo |first8=Arie |last9=Kujala |first9=Pekka |last10=Peters |first10=Peter J. |last11=Clevers |first11=Hans |title=Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche |journal=Nature |date=2009 |volume=459 |issue=7244 |pages=262–265 |doi=10.1038/nature07935 |pmid=19329995 |bibcode=2009Natur.459..262S |s2cid=4373784 |url=https://www.nature.com/articles/nature07935 |access-date=23 June 2022 |url-access=subscription}}</ref> Clevers's group has applied this technology to [[Cell culture|culturing]] organoids from other organs, such as the stomach<ref name="stomachorganoid"/> and [[liver]],<ref>{{cite journal |first1=Meritxell |last1=Huch |first2=Craig |last2=Dorrell |first3=Sylvia F. |last3=Boj |first4=Johan H. |last4=van Es |first5=Marc |last5=van de Wetering |first6=Vivian S.W. |last6=Li |first7=Karien |last7=Hamer |first8=Nobuo |last8=Sasaki |first9=Milton J. |last9=Finegold |first10=Annelise |last10=Haft |first11=Markus |last11=Grompe |first12=Hans |last12=Clevers |title=In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration |journal=Nature |date=2013 |volume=494 |issue=7436 |pages=247–250 |doi=10.1038/nature11826 |pmid=23354049 |pmc=3634804 |bibcode=2013Natur.494..247H }}</ref> as well as from various [[cancer]] types, including cancer of the [[Breast cancer|breast]]<ref>{{cite journal |first1=Norman |last1=Sachs |first2=Joep |last2=de Ligt |first3=Oded |last3=Kopper |first4=Ewa |last4=Gogola |first5=Gergana |last5=Bounova |first6=Fleur |last6=Weeber |first7=Anjali |last7=Vanita Balgobind |first8=Karin |last8=Wind |first9=Ana |last9=Gracanin |first10=Harry |last10=Begthel |first11=Jeroen |last11=Korving |first12=Ruben |last12=van Boxtel |first13=Alexandra |last13=Alves Duarte |first14=Daphne |last14=Lelieveld |first15=Arne |last15=van Hoeck |first16=Robert Frans |last16=Ernst |first17=Francis |last17=Blokzijl |first18=Isaac Johannes |last18=Nijman |first19=Marlous |last19=Hoogstraat |first20=Marieke |last20=van de Ven |first21=David Anthony |last21=Egan |first22=Vittoria |last22=Zinzalla |first23=Jurgen |last23=Moll |first24=Sylvia |last24=Fernandez Boj |first25=Emile Eugene |last25=Voest |first26=Lodewyk |last26=Wessels |first27=Paul Joannes |last27=van Diest |first28=Sven |last28=Rottenberg |first29=Robert Gerhardus Jacob |last29=Vries |first30=Edwin |last30=Cuppen |first31=Hans |last31=Clevers |title=A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity |journal=[[Cell (journal)|Cell]] |date=2018 |volume=172 |issue=1–2 |pages=373–386 |doi=10.1016/j.cell.2017.11.010 |pmid=29224780 |s2cid=8951522 |archive-url=https://archive.today/20220629070021/https://www.sciencedirect.com/science/article/pii/S0092867417313193 |archive-date=29 June 2022 |url=https://www.sciencedirect.com/science/article/pii/S0092867417313193 |access-date=29 June 2022|doi-access=free }}</ref> and the [[Ovarian cancer|ovaries]].<ref>{{cite journal |first1=Oded |last1=Kopper |first2=Chris J. |last2=de Witte |first3=Kadi |last3=Lõhmussaar |first4=Jose Espejo |last4=Valle-Inclan |first5=Nizar |last5=Hami |first6=Lennart |last6=Kester |first7=Anjali |last7=Vanita Balgobind |first8=Jeroen |last8=Korving |first9=Natalie |last9=Proost |first10=Harry |last10=Begthel |first11=Lise M |last11=van Wijk |first12=Sonia |last12=Aristín Revilla |first13=Rebecca |last13=Theeuwsen |first14=Marieke |last14=van de Ven |first15=Markus J |last15=van Roosmalen |first16=Bas |last16=Ponsioen |first17=Victor W. H. |last17=Ho |first18=Benjamin G. |last18=Neel |first19=Tjalling |last19=Bosse |first20=Katja N. |last20=Gaarenstroom |first21=Harry |last21=Vrieling |first22=Maaike P. G. |last22=Vreeswijk |first23=Paul J. |last23=van Diest |first24=Petronella O. |last24=Witteveen |first25=Trudy |last25=Jonges |first26=Johannes L. |last26=Bos |first27=Alexander |last27=van Oudenaarden |first28=Ronald P. |last28=Zweemer |first29=Hugo J. G. |last29=Snippert |first30=Wigard P. |last30=Kloosterman 14, Hans Clevers |title=An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity |journal=[[Nature Medicine]] |date=2019 |volume=25 |issue=5 |pages=838–849 |doi=10.1038/s41591-019-0422-6 |pmid=31011202 |s2cid=126428230 |url=https://www.nature.com/articles/s41591-019-0422-6 |access-date=29 June 2022 |url-access=subscription}}</ref> This platform has since been applied in [[personalized medicine]], by generating organoids from specific patients to screen for drugs.<ref>{{cite journal |last1=Bartfeld |first1=Sina |title=Realizing the potential of organoids—an interview with Hans Clevers |journal=[[Journal of Molecular Medicine]] |date=2021 |volume=99 |issue=4 |pages=443–447 |doi=10.1007/s00109-020-02025-3 |pmid=33464358 |pmc=8026466 }}</ref><ref>{{cite journal |last1=Bender |first1=Eric |title=Q&A: Hans Clevers |journal=Nature |date=2015 |volume=521 |issue=7551 |page=S15 |doi=10.1038/521S15a |pmid=25970453 |bibcode=2015Natur.521S..15B |s2cid=4452738 |url=https://www.nature.com/articles/521S15a |access-date=29 June 2022 |archive-date=29 June 2022 |archive-url=https://web.archive.org/web/20220629064516/https://www.nature.com/articles/521S15a|doi-access=free }}</ref> This is not limited to cancer but is applicable to other diseases as well (for example, cystic fibrosis).<ref>{{cite journal |last1=Saini |first1=Angela |title=Cystic Fibrosis Patients Benefit from Mini Guts |journal=Cell Stem Cell |date=2016 |volume=19 |issue=4 |pages=425–427 |doi=10.1016/j.stem.2016.09.001 |url=https://www.cell.com/cell-stem-cell/pdf/S1934-5909(16)30295-8.pdf |access-date=26 June 2022 |archive-date=25 June 2022 |archive-url=https://web.archive.org/web/20220625160459/https://www.cell.com/cell-stem-cell/pdf/S1934-5909(16)30295-8.pdf}}</ref> His current major research interest is in using organoids derived from adult stem cells to study the molecular mechanism of [[Tissue growth|tissue]] and [[Carcinogenesis|cancer development]].
Building on this discovery, in 2009, his group published a landmark paper, describing for the first time how [[organoid]]s, which are [[Three-dimensional space|3-dimensional]] ''[[in vitro]]'' structures that behave [[Anatomy|anatomically]] and [[Molecular biology|molecularly]] like the organ from which they are derived, were generated from [[adult stem cell]]s, creating organoids of the [[small intestine]].<ref>{{cite journal |last1=Sato |first1=Toshiro |last2=Vries |first2=Robert G. |last3=Snippert |first3=Hugo J. |last4=van de Wetering |first4=Marc |last5=Barker |first5=Nick |last6=Stange |first6=Daniel E. |last7=van Es |first7=Johan H. |last8=Abo |first8=Arie |last9=Kujala |first9=Pekka |last10=Peters |first10=Peter J. |last11=Clevers |first11=Hans |title=Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche |journal=Nature |date=2009 |volume=459 |issue=7244 |pages=262–265 |doi=10.1038/nature07935 |pmid=19329995 |bibcode=2009Natur.459..262S |s2cid=4373784 |url=https://www.nature.com/articles/nature07935 |access-date=23 June 2022 |url-access=subscription}}</ref> Clevers's group has applied this technology to [[Cell culture|culturing]] organoids from other organs, such as the stomach<ref name="stomachorganoid"/> and [[liver]],<ref>{{cite journal |first1=Meritxell |last1=Huch |first2=Craig |last2=Dorrell |first3=Sylvia F. |last3=Boj |first4=Johan H. |last4=van Es |first5=Marc |last5=van de Wetering |first6=Vivian S.W. |last6=Li |first7=Karien |last7=Hamer |first8=Nobuo |last8=Sasaki |first9=Milton J. |last9=Finegold |first10=Annelise |last10=Haft |first11=Markus |last11=Grompe |first12=Hans |last12=Clevers |title=In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration |journal=Nature |date=2013 |volume=494 |issue=7436 |pages=247–250 |doi=10.1038/nature11826 |pmid=23354049 |pmc=3634804 |bibcode=2013Natur.494..247H }}</ref> as well as from various [[cancer]] types, including cancer of the [[Breast cancer|breast]]<ref>{{cite journal |first1=Norman |last1=Sachs |first2=Joep |last2=de Ligt |first3=Oded |last3=Kopper |first4=Ewa |last4=Gogola |first5=Gergana |last5=Bounova |first6=Fleur |last6=Weeber |first7=Anjali |last7=Vanita Balgobind |first8=Karin |last8=Wind |first9=Ana |last9=Gracanin |first10=Harry |last10=Begthel |first11=Jeroen |last11=Korving |first12=Ruben |last12=van Boxtel |first13=Alexandra |last13=Alves Duarte |first14=Daphne |last14=Lelieveld |first15=Arne |last15=van Hoeck |first16=Robert Frans |last16=Ernst |first17=Francis |last17=Blokzijl |first18=Isaac Johannes |last18=Nijman |first19=Marlous |last19=Hoogstraat |first20=Marieke |last20=van de Ven |first21=David Anthony |last21=Egan |first22=Vittoria |last22=Zinzalla |first23=Jurgen |last23=Moll |first24=Sylvia |last24=Fernandez Boj |first25=Emile Eugene |last25=Voest |first26=Lodewyk |last26=Wessels |first27=Paul Joannes |last27=van Diest |first28=Sven |last28=Rottenberg |first29=Robert Gerhardus Jacob |last29=Vries |first30=Edwin |last30=Cuppen |first31=Hans |last31=Clevers |title=A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity |journal=[[Cell (journal)|Cell]] |date=2018 |volume=172 |issue=1–2 |pages=373–386 |doi=10.1016/j.cell.2017.11.010 |pmid=29224780 |s2cid=8951522 |doi-access=free }}</ref> and the [[Ovarian cancer|ovaries]].<ref>{{cite journal |first1=Oded |last1=Kopper |first2=Chris J. |last2=de Witte |first3=Kadi |last3=Lõhmussaar |first4=Jose Espejo |last4=Valle-Inclan |first5=Nizar |last5=Hami |first6=Lennart |last6=Kester |first7=Anjali |last7=Vanita Balgobind |first8=Jeroen |last8=Korving |first9=Natalie |last9=Proost |first10=Harry |last10=Begthel |first11=Lise M |last11=van Wijk |first12=Sonia |last12=Aristín Revilla |first13=Rebecca |last13=Theeuwsen |first14=Marieke |last14=van de Ven |first15=Markus J |last15=van Roosmalen |first16=Bas |last16=Ponsioen |first17=Victor W. H. |last17=Ho |first18=Benjamin G. |last18=Neel |first19=Tjalling |last19=Bosse |first20=Katja N. |last20=Gaarenstroom |first21=Harry |last21=Vrieling |first22=Maaike P. G. |last22=Vreeswijk |first23=Paul J. |last23=van Diest |first24=Petronella O. |last24=Witteveen |first25=Trudy |last25=Jonges |first26=Johannes L. |last26=Bos |first27=Alexander |last27=van Oudenaarden |first28=Ronald P. |last28=Zweemer |first29=Hugo J. G. |last29=Snippert |first30=Wigard P. |last30=Kloosterman 14, Hans Clevers |title=An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity |journal=[[Nature Medicine]] |date=2019 |volume=25 |issue=5 |pages=838–849 |doi=10.1038/s41591-019-0422-6 |pmid=31011202 |s2cid=126428230 |url=https://www.nature.com/articles/s41591-019-0422-6 |access-date=29 June 2022 |url-access=subscription}}</ref> This platform has since been applied in [[personalized medicine]], by generating organoids from specific patients to screen for drugs.<ref>{{cite journal |last1=Bartfeld |first1=Sina |title=Realizing the potential of organoids—an interview with Hans Clevers |journal=[[Journal of Molecular Medicine]] |date=2021 |volume=99 |issue=4 |pages=443–447 |doi=10.1007/s00109-020-02025-3 |pmid=33464358 |pmc=8026466 }}</ref><ref>{{cite journal |last1=Bender |first1=Eric |title=Q&A: Hans Clevers |journal=Nature |date=2015 |volume=521 |issue=7551 |page=S15 |doi=10.1038/521S15a |pmid=25970453 |bibcode=2015Natur.521S..15B |s2cid=4452738 |doi-access=free }}</ref> This is not limited to cancer but is applicable to other diseases as well (for example, cystic fibrosis).<ref>{{cite journal |last1=Saini |first1=Angela |title=Cystic Fibrosis Patients Benefit from Mini Guts |journal=Cell Stem Cell |date=2016 |volume=19 |issue=4 |pages=425–427 |doi=10.1016/j.stem.2016.09.001 |url=https://www.cell.com/cell-stem-cell/pdf/S1934-5909(16)30295-8.pdf |access-date=26 June 2022 |archive-date=25 June 2022 |archive-url=https://web.archive.org/web/20220625160459/https://www.cell.com/cell-stem-cell/pdf/S1934-5909(16)30295-8.pdf}}</ref> His current major research interest is in using organoids derived from adult stem cells to study the molecular mechanism of [[Tissue growth|tissue]] and [[Carcinogenesis|cancer development]].


During the [[COVID-19 pandemic]], Clevers's group modelled the infection of [[SARS-CoV-2]] using [[lung]] organoids.<ref>{{cite journal |first1=Mart M |last1=Lamers |first2=Jelte |last2=van der Vaart |first3=Kèvin |last3=Knoops |first4=Samra |last4=Riesebosch |first5=Tim I |last5=Breugem |first6=Anna Z |last6=Mykytyn |first7=Joep |last7=Beumer |first8=Debby |last8=Schipper |first9=Karel |last9=Bezstarosti |first10=Charlotte D |last10=Koopman |first11=Nathalie |last11=Groen |first12=Raimond B G |last12=Ravelli |first13=Hans Q |last13=Duimel |first14=Jeroen A A |last14=Demmers |first15=Georges M G M |last15=Verjans |first16=Marion P G |last16=Koopmans |first17=Mauro J |last17=Muraro |first18=Peter J |last18=Peters |first19=Hans |last19=Clevers |first20=Bart L |last20=Haagmans |title=An organoid‐derived bronchioalveolar model for SARS‐CoV‐2 infection of human alveolar type II‐like cells |journal=The EMBO Journal |date=2021 |volume=40 |issue=5 |page=e105912 |doi=10.15252/embj.2020105912 |pmid=33283287 |pmc=7883112 }}</ref>
During the [[COVID-19 pandemic]], Clevers's group modelled the infection of [[SARS-CoV-2]] using [[lung]] organoids.<ref>{{cite journal |first1=Mart M |last1=Lamers |first2=Jelte |last2=van der Vaart |first3=Kèvin |last3=Knoops |first4=Samra |last4=Riesebosch |first5=Tim I |last5=Breugem |first6=Anna Z |last6=Mykytyn |first7=Joep |last7=Beumer |first8=Debby |last8=Schipper |first9=Karel |last9=Bezstarosti |first10=Charlotte D |last10=Koopman |first11=Nathalie |last11=Groen |first12=Raimond B G |last12=Ravelli |first13=Hans Q |last13=Duimel |first14=Jeroen A A |last14=Demmers |first15=Georges M G M |last15=Verjans |first16=Marion P G |last16=Koopmans |first17=Mauro J |last17=Muraro |first18=Peter J |last18=Peters |first19=Hans |last19=Clevers |first20=Bart L |last20=Haagmans |title=An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells |journal=The EMBO Journal |date=2021 |volume=40 |issue=5 |page=e105912 |doi=10.15252/embj.2020105912 |pmid=33283287 |pmc=7883112 }}</ref>


== Honours and awards ==
== Honours and awards ==

Revision as of 00:00, 29 March 2024

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 materUniversity of Utrecht
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 the University of Utrecht.[8]

Early life and education

Hans Clevers was born in Eindhoven, the Netherlands in 1957.[5] He began studying biology at the University of Utrecht 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

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, the University of Utrecht, 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 the University of Utrecht.[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 the University of Utrecht 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

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

References

  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). University of Utrecht. 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". University of Utrecht. 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.
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