Hans Clevers

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Johannes (Hans) Carolus Clevers (born 27 March 1957)[1][2] 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.[3][4] Previously, he headed a research group at the Hubrecht Institute for Developmental Biology and Stem Cell Research[5] and at the Princess Máxima Center [nl];[6] he remained as an advisor and guest scientist or visiting researcher to both groups.[3] He is also a Professor in Molecular Genetics at Utrecht University.[4]

Early life and education

Hans Clevers was born in Eindhoven, the Netherlands in 1957.[7] He began studying biology at Utrecht University in 1975, but also started taking medicine in 1978,[3] in part due to his interest and in part because his friends and brothers were in the medical profession.[8] He spent 1 year in Nairobi, Kenya, and half a year at the National Institutes of Health in Bethesda, United States, for biology rotations.[8][9] 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.[10][11][12] He obtained his PhD 1 year later.[3][8]

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Career

After his PhD, Clevers went to the Dana–Farber Cancer Institute as a postdoctoral researcher at Cox Terhorst's group.[4][8][13][14] In 1989, he returned to the Netherlands, joining his alma mater, Utrecht University, as an assistant professor at the Department of Clinical Immunology.[4]

In 1991, Clevers became a professor and the chair of the Department of Immunology at Utrecht University.[4] 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).[3] At the same time, he took up the position of Director of the Hubrecht Institute.[4]

In March 2012, Clevers was elected the president of the Royal Netherlands Academy of Arts and Sciences, succeeding Robbert Dijkgraaf.[15][16] His term concluded in 2015, and he started another lab at the Princess Máxima Center [nl],[4] focusing on childhood cancer,[6] and became the Director Research and Chief Scientific Officer there until 2019.[4]

Clevers left University Medical Center Utrecht and was appointed Professor in Molecular Genetics at Utrecht University in 2020.[3]

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.[17][18] He remains an advisor and guest scientist or visiting researcher to his research groups at the Princess Máxima Center and Hubrecht Institute.[5][6]

Since 2017, Clevers is an investigator at the Oncode Institute in Utrecht.[3][19]

Clevers has served at a number of scientific organizations, including on the board of directors of the American Association for Cancer Research (2013-2016),[20] and the Scientific Advisory Board of the Swiss Institute for Experimental Cancer Research at the École Polytechnique Fédérale de Lausanne (2005-2015),[4] the Research Institute of Molecular Pathology in Vienna (2015-2021)[21] and the Francis Crick Institute in London.[22] He is currently on the advisory board of various scientific journals, including The EMBO Journal,[23] Disease Models & Mechanisms,[24] Cell,[25] Cell Stem Cell[26] and EMBO Molecular Medicine.[27] From 2014 to 2022, he was also on the editorial committee of the Annual Review of Cancer Biology.[3]

Outside the academia, Clevers has been a scientific advisor to numerous biotechnology companies.[3] He also co-founded California-based Surrozen[28] in 2016[29] and Shanghai-based D1 Medical Technology[30] in 2019.[31]

File:Chemist Hans Clevers replaces worn-down body parts with organoids created outside the body-VPRO-The Mind of the Universe.ogv

Research

Clevers's early career focused on the Wnt signaling pathway.[32] 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.[33] His interest in the gastrointestinal tract began with the discovery that another TCF family member, the TCF4 protein, is required in forming intestinal crypts.[34] 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,[35] 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.[36] This led to his finding that LGR5 is a stem cell marker in other organs as well, including the stomach[37] and hair follicles.[38]

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.[39] Clevers's group has applied this technology to culturing organoids from other organs, such as the stomach[37] and liver,[40] as well as from various cancer types, including cancer of the breast[41] and the ovaries.[42] This platform has since been applied in personalized medicine, by generating organoids from specific patients to screen for drugs.[43][44] This is not limited to cancer but is applicable to other diseases as well (for example, cystic fibrosis).[45] 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.[46]

Honours and awards

References

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  2. ^ Cite error: The named reference catalogus was invoked but never defined (see the help page).
  3. ^ a b c d e f g h i j Page Module:Citation/CS1/styles.css has no content."CURRICULUM VITAE" (PDF). Utrecht University. Archived from the original (PDF) on 23 June 2022. Retrieved 23 June 2022.
  4. ^ a b c d e f g h i Page Module:Citation/CS1/styles.css has no content."Prof. Dr. Hans Clevers". Roche. Retrieved 23 June 2022.{{cite web}}: CS1 maint: deprecated archival service (link)
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  6. ^ a b c Page Module:Citation/CS1/styles.css has no content."Clevers group". Princess Máxima Center [nl]. Archived from the original on 23 June 2022. Retrieved 23 June 2022.
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  8. ^ a b c d Page Module:Citation/CS1/styles.css has no content.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.
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  14. ^ Page Module:Citation/CS1/styles.css has no content."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.
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  33. ^ Page Module:Citation/CS1/styles.css has no content.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.
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  37. ^ a b Page Module:Citation/CS1/styles.css has no content.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.
  38. ^ Page Module:Citation/CS1/styles.css has no content.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.
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  41. ^ Page Module:Citation/CS1/styles.css has no content.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.
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