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2. Epidermal growth factor receptor (EGFR) is a target of the tumor-suppressor E3 ligase FBXW7

Author

Boretto, Matteo, primary, Geurts, Maarten H., additional, Gandhi, Shashank, additional, Ma, Ziliang, additional, Staliarova, Nadzeya, additional, Celotti, Martina, additional, Lim, Sangho, additional, He, Gui-Wei, additional, Millen, Rosemary, additional, Driehuis, Else, additional, Begthel, Harry, additional, Smabers, Lidwien, additional, Roodhart, Jeanine, additional, van Es, Johan, additional, Wu, Wei, additional, and Clevers, Hans, additional

Published
2024
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3. Epidermal growth factor receptor (EGFR) is a target of the tumor-suppressor E3 ligase FBXW7

Author

Onderzoek Medische Oncologie, Cancer, MS Medische Oncologie, CMM, Hubrecht Institute with UMC, Boretto, Matteo, Geurts, Maarten H, Gandhi, Shashank, Ma, Ziliang, Staliarova, Nadzeya, Celotti, Martina, Lim, Sangho, He, Gui-Wei, Millen, Rosemary, Driehuis, Else, Begthel, Harry, Smabers, Lidwien, Roodhart, Jeanine, van Es, Johan, Wu, Wei, Clevers, Hans, Onderzoek Medische Oncologie, Cancer, MS Medische Oncologie, CMM, Hubrecht Institute with UMC, Boretto, Matteo, Geurts, Maarten H, Gandhi, Shashank, Ma, Ziliang, Staliarova, Nadzeya, Celotti, Martina, Lim, Sangho, He, Gui-Wei, Millen, Rosemary, Driehuis, Else, Begthel, Harry, Smabers, Lidwien, Roodhart, Jeanine, van Es, Johan, Wu, Wei, and Clevers, Hans

Published
2024

4. Epidermal growth factor receptor (EGFR) is a target of the tumor-suppressor E3 ligase FBXW7

Author

Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Boretto, Matteo, Geurts, Maarten H., Gandhi, Shashank, Ma, Ziliang, Staliarova, Nadzeya, Celotti, Martina, Lim, Sangho, He, Gui Wei, Millen, Rosemary, Driehuis, Else, Begthel, Harry, Smabers, Lidwien, Roodhart, Jeanine, van Es, Johan, Wu, Wei, Clevers, Hans, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Boretto, Matteo, Geurts, Maarten H., Gandhi, Shashank, Ma, Ziliang, Staliarova, Nadzeya, Celotti, Martina, Lim, Sangho, He, Gui Wei, Millen, Rosemary, Driehuis, Else, Begthel, Harry, Smabers, Lidwien, Roodhart, Jeanine, van Es, Johan, Wu, Wei, and Clevers, Hans

Published
2024

6. Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease

Author

Mayr, Lisa, Grabherr, Felix, Schwärzler, Julian, Reitmeier, Isabelle, Sommer, Felix, Gehmacher, Thomas, Niederreiter, Lukas, He, Gui-Wei, Ruder, Barbara, Kunz, Kai T. R., Tymoszuk, Piotr, Hilbe, Richard, Haschka, David, Feistritzer, Clemens, Gerner, Romana R., Enrich, Barbara, Przysiecki, Nicole, Seifert, Markus, Keller, Markus A., Oberhuber, Georg, Sprung, Susanne, Ran, Qitao, Koch, Robert, Effenberger, Maria, Tancevski, Ivan, Zoller, Heinz, Moschen, Alexander R., Weiss, Günter, Becker, Christoph, Rosenstiel, Philip, Kaser, Arthur, Tilg, Herbert, and Adolph, Timon E.

Published
2020
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8. Data from Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

Author

Driehuis, Else, primary, Kolders, Sigrid, primary, Spelier, Sacha, primary, Lõhmussaar, Kadi, primary, Willems, Stefan M., primary, Devriese, Lot A., primary, de Bree, Remco, primary, de Ruiter, Emma J., primary, Korving, Jeroen, primary, Begthel, Harry, primary, van Es, Johan H., primary, Geurts, Veerle, primary, He, Gui-Wei, primary, van Jaarsveld, Richard H., primary, Oka, Rurika, primary, Muraro, Mauro J., primary, Vivié, Judith, primary, Zandvliet, Maurice M.J.M., primary, Hendrickx, Antoni P.A., primary, Iakobachvili, Nino, primary, Sridevi, Priya, primary, Kranenburg, Onno, primary, van Boxtel, Ruben, primary, Kops, Geert J.P.L., primary, Tuveson, David A., primary, Peters, Peter J., primary, van Oudenaarden, Alexander, primary, and Clevers, Hans, primary

Published
2023
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9. Movie S1 from Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

Author

Driehuis, Else, primary, Kolders, Sigrid, primary, Spelier, Sacha, primary, Lõhmussaar, Kadi, primary, Willems, Stefan M., primary, Devriese, Lot A., primary, de Bree, Remco, primary, de Ruiter, Emma J., primary, Korving, Jeroen, primary, Begthel, Harry, primary, van Es, Johan H., primary, Geurts, Veerle, primary, He, Gui-Wei, primary, van Jaarsveld, Richard H., primary, Oka, Rurika, primary, Muraro, Mauro J., primary, Vivié, Judith, primary, Zandvliet, Maurice M.J.M., primary, Hendrickx, Antoni P.A., primary, Iakobachvili, Nino, primary, Sridevi, Priya, primary, Kranenburg, Onno, primary, van Boxtel, Ruben, primary, Kops, Geert J.P.L., primary, Tuveson, David A., primary, Peters, Peter J., primary, van Oudenaarden, Alexander, primary, and Clevers, Hans, primary

Published
2023
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10. Supplementary Data from Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

Author

Driehuis, Else, primary, Kolders, Sigrid, primary, Spelier, Sacha, primary, Lõhmussaar, Kadi, primary, Willems, Stefan M., primary, Devriese, Lot A., primary, de Bree, Remco, primary, de Ruiter, Emma J., primary, Korving, Jeroen, primary, Begthel, Harry, primary, van Es, Johan H., primary, Geurts, Veerle, primary, He, Gui-Wei, primary, van Jaarsveld, Richard H., primary, Oka, Rurika, primary, Muraro, Mauro J., primary, Vivié, Judith, primary, Zandvliet, Maurice M.J.M., primary, Hendrickx, Antoni P.A., primary, Iakobachvili, Nino, primary, Sridevi, Priya, primary, Kranenburg, Onno, primary, van Boxtel, Ruben, primary, Kops, Geert J.P.L., primary, Tuveson, David A., primary, Peters, Peter J., primary, van Oudenaarden, Alexander, primary, and Clevers, Hans, primary

Published
2023
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11. The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

Author

Gunther, Claudia, He, Gui-Wei, Kremer, Andreas E., Murphy, James M., Petrie, Emma J., Amann, Kerstin, Vandenabeele, Peter, Linkermann, Andreas, Poremba, Christopher, Schleicher, Ulrike, Dewitz, Christin, Krautwald, Stefan, Neurath, Markus F., Becker, Christoph, and Wirtz, Stefan

Subjects
Inflammation -- Analysis, Hepatoma -- Risk factors, Necrosis -- Analysis, Health care industry
Abstract

Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain-like protein (MLKL), which plays a key role in the execution of receptor-interacting protein (RIP) kinase-dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-γ in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases., Introduction Although the liver is an organ of remarkable regenerative capacity, cell death-related compensatory tissue injury responses commonly culminate in fibrosis and eventually cirrhosis, a major cause of morbidity worldwide. [...]

Published
2016
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13. Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

Author

Groep Holstege, CMM Groep Burgering, Cancer, CMM, Hubrecht Institute with UMC, He, Gui Wei, Lin, Lin, DeMartino, Jeff, Zheng, Xuan, Staliarova, Nadzeya, Dayton, Talya, Begthel, Harry, van de Wetering, Willine J., Bodewes, Eduard, van Zon, Jeroen, Tans, Sander, Lopez-Iglesias, Carmen, Peters, Peter J., Wu, Wei, Kotlarz, Daniel, Klein, Christoph, Margaritis, Thanasis, Holstege, Frank, Clevers, Hans, Groep Holstege, CMM Groep Burgering, Cancer, CMM, Hubrecht Institute with UMC, He, Gui Wei, Lin, Lin, DeMartino, Jeff, Zheng, Xuan, Staliarova, Nadzeya, Dayton, Talya, Begthel, Harry, van de Wetering, Willine J., Bodewes, Eduard, van Zon, Jeroen, Tans, Sander, Lopez-Iglesias, Carmen, Peters, Peter J., Wu, Wei, Kotlarz, Daniel, Klein, Christoph, Margaritis, Thanasis, Holstege, Frank, and Clevers, Hans

Published
2022

15. Interferon Lambda Promotes Paneth Cell Death Via STAT1 Signaling in Mice and Is Increased in Inflamed Ileal Tissues of Patients With Crohn’s Disease

Author

Günther, Claudia, primary, Ruder, Barbara, additional, Stolzer, Iris, additional, Dorner, Heidrun, additional, He, Gui-Wei, additional, Chiriac, Mircea Teodor, additional, Aden, Konrad, additional, Strigli, Anne, additional, Bittel, Miriam, additional, Zeissig, Sebastian, additional, Rosenstiel, Philip, additional, Atreya, Raja, additional, Neurath, Markus F., additional, Wirtz, Stefan, additional, and Becker, Christoph, additional

Published
2019
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16. Oral mucosal organoids as a potential platform for personalized cancer therapy

Author

Driehuis, Else, Kolders, Sigrid, Spelier, Sacha, Lohmussaar, Kadi, Willems, Stefan M, Devriese, Lot A, de Bree, Remco, de Ruiter, Emma J, Korving, Jeroen, Begthel, Harry, Van Es, Johan H, Geurts, Veerle, He, Gui-Wei, van Jaarsveld, Richard H, Oka, Rurika, Muraro, Mauro J, Vivie, Judith, Zandvliet, Maurice M J M, Hendrickx, Antoni P A, Iakobachvili, Nino, Sridevi, Priya, Kranenburg, Onno, van Boxtel, Ruben, Kops, Geert J P L, Tuveson, David A, Peters, Peter J, van Oudenaarden, Alexander, Clevers, Hans, Sub Clinical Pharmacology, Sub Oncologie/Cytologie, dCSCA RMSC-2, Sub Developmental Biology, Faculteit Diergeneeskunde, RS: M4I - Nanoscopy, Institute of Nanoscopy (IoN), Hubrecht Institute for Developmental Biology and Stem Cell Research, Sub Clinical Pharmacology, Sub Oncologie/Cytologie, dCSCA RMSC-2, Sub Developmental Biology, and Faculteit Diergeneeskunde

Subjects
0301 basic medicine, medicine.medical_treatment, Cetuximab, Mice, SCID, Carboplatin, Mice, chemistry.chemical_compound, 0302 clinical medicine, Mice, Inbred NOD, HUMAN HEAD, Antineoplastic Combined Chemotherapy Protocols, Precision Medicine, GENE-EXPRESSION, INHIBITOR, Chemoradiotherapy, Organoids, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, SQUAMOUS-CELL CARCINOMA, medicine.drug, Xenotransplantation, MODELS, 03 medical and health sciences, stomatognathic system, Journal Article, Carcinoma, medicine, Organoid, otorhinolaryngologic diseases, Animals, Humans, neoplasms, Cisplatin, Squamous Cell Carcinoma of Head and Neck, business.industry, HUMAN-PAPILLOMAVIRUS, Mouth Mucosa, IN-VITRO, medicine.disease, Xenograft Model Antitumor Assays, Head and neck squamous-cell carcinoma, Radiation therapy, stomatognathic diseases, 030104 developmental biology, chemistry, Cancer research, Drug Screening Assays, Antitumor, GROWTH-FACTOR RECEPTOR, business
Abstract

Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)–derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy in vitro. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs.Significance:This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. In vitro drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice.See related commentary by Hill and D'Andrea, p. 828.This article is highlighted in the In This Issue feature, p. 813

Published
2019

17. Oral mucosal organoids as a potential platform for personalized cancer therapy

Author

Sub Clinical Pharmacology, Sub Oncologie/Cytologie, dCSCA RMSC-2, Sub Developmental Biology, Faculteit Diergeneeskunde, Driehuis, Else, Kolders, Sigrid, Spelier, Sacha, Lohmussaar, Kadi, Willems, Stefan M, Devriese, Lot A, de Bree, Remco, de Ruiter, Emma J, Korving, Jeroen, Begthel, Harry, Van Es, Johan H, Geurts, Veerle, He, Gui-Wei, van Jaarsveld, Richard H, Oka, Rurika, Muraro, Mauro J, Vivie, Judith, Zandvliet, Maurice M J M, Hendrickx, Antoni P A, Iakobachvili, Nino, Sridevi, Priya, Kranenburg, Onno, van Boxtel, Ruben, Kops, Geert J P L, Tuveson, David A, Peters, Peter J, van Oudenaarden, Alexander, Clevers, Hans, Sub Clinical Pharmacology, Sub Oncologie/Cytologie, dCSCA RMSC-2, Sub Developmental Biology, Faculteit Diergeneeskunde, Driehuis, Else, Kolders, Sigrid, Spelier, Sacha, Lohmussaar, Kadi, Willems, Stefan M, Devriese, Lot A, de Bree, Remco, de Ruiter, Emma J, Korving, Jeroen, Begthel, Harry, Van Es, Johan H, Geurts, Veerle, He, Gui-Wei, van Jaarsveld, Richard H, Oka, Rurika, Muraro, Mauro J, Vivie, Judith, Zandvliet, Maurice M J M, Hendrickx, Antoni P A, Iakobachvili, Nino, Sridevi, Priya, Kranenburg, Onno, van Boxtel, Ruben, Kops, Geert J P L, Tuveson, David A, Peters, Peter J, van Oudenaarden, Alexander, and Clevers, Hans

Published
2019

18. Oral mucosal organoids as a potential platform for personalized cancer therapy

Author

Pathologie Patiëntenadministratie, UMC Utrecht, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, MS Hoofd-Hals Chirurgische Oncologie, Pathologie Groep Moelans, Hubrecht Institute with UMC, MMB Infectiepreventie, Infection & Immunity, CMM Groep Coffer, MS CGO, Regenerative Medicine and Stem Cells, CMM Groep Cuppen, CMM Sectie Molecular Cancer Research, Child Health, Driehuis, Else, Kolders, Sigrid, Spelier, Sacha, Lõhmussaar, Kadi, Willems, Stefan M., Devriese, Lot A., de Bree, Remco, de Ruiter, Emma J., Korving, Jeroen, Begthel, Harry, van Es, Johan H., Geurts, Veerle, He, Gui Wei, van Jaarsveld, Richard H., Oka, Rurika, Muraro, Mauro J., Vivié, Judith, Zandvliet, Maurice M.J.M., Hendrickx, Antoni P.A., Iakobachvili, Nino, Sridevi, Priya, Kranenburg, Onno, van Boxtel, Ruben, Kops, Geert J.P.L., Tuveson, David A., Peters, Peter J., van Oudenaarden, Alexander, Clevers, Hans, Pathologie Patiëntenadministratie, UMC Utrecht, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, MS Hoofd-Hals Chirurgische Oncologie, Pathologie Groep Moelans, Hubrecht Institute with UMC, MMB Infectiepreventie, Infection & Immunity, CMM Groep Coffer, MS CGO, Regenerative Medicine and Stem Cells, CMM Groep Cuppen, CMM Sectie Molecular Cancer Research, Child Health, Driehuis, Else, Kolders, Sigrid, Spelier, Sacha, Lõhmussaar, Kadi, Willems, Stefan M., Devriese, Lot A., de Bree, Remco, de Ruiter, Emma J., Korving, Jeroen, Begthel, Harry, van Es, Johan H., Geurts, Veerle, He, Gui Wei, van Jaarsveld, Richard H., Oka, Rurika, Muraro, Mauro J., Vivié, Judith, Zandvliet, Maurice M.J.M., Hendrickx, Antoni P.A., Iakobachvili, Nino, Sridevi, Priya, Kranenburg, Onno, van Boxtel, Ruben, Kops, Geert J.P.L., Tuveson, David A., Peters, Peter J., van Oudenaarden, Alexander, and Clevers, Hans

Published
2019

22. Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection

Author

Mahapatro, Mousumi, primary, Foersch, Sebastian, additional, Hefele, Manuela, additional, He, Gui-Wei, additional, Giner-Ventura, Elisa, additional, Mchedlidze, Tamar, additional, Kindermann, Markus, additional, Vetrano, Stefania, additional, Danese, Silvio, additional, Günther, Claudia, additional, Neurath, Markus F., additional, Wirtz, Stefan, additional, and Becker, Christoph, additional

Published
2016
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23. Caspase-8 controls the gut response to microbial challenges by Tnf-α-dependent and independent pathways

Author

Günther, Claudia, primary, Buchen, Barbara, additional, He, Gui-Wei, additional, Hornef, Mathias, additional, Torow, Natalia, additional, Neumann, Helmut, additional, Wittkopf, Nadine, additional, Martini, Eva, additional, Basic, Marijana, additional, Bleich, André, additional, Watson, Alastair J M, additional, Neurath, Markus F, additional, and Becker, Christoph, additional

Published
2014
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24. Intestinal epithelial Caspase-8 signaling is essential to prevent necroptosis during SalmonellaTyphimurium induced enteritis

Author

Hefele, Manuela, Stolzer, Iris, Ruder, Barbara, He, Gui-Wei, Mahapatro, Mousumi, Wirtz, Stefan, Neurath, Markus, and Günther, Claudia

Abstract

Although induction of host cell death is a pivotal step during bacteria-induced gastroenteritis, the molecular regulation remains to be fully characterized. To expand our knowledge, we investigated the role of the central cell death regulator Caspase-8 in response to SalmonellaTyphimurium. Here, we uncovered that intestinal salmonellosiswas associated with strong upregulation of members of the host cell death machinery in intestinal epithelial cells (IECs) as an early event, suggesting that elimination of infected IECs represents a host defense strategy. Indeed, Casp8∆IECmice displayed severe tissue damage and high lethality after infection. Additional deletion of Ripk3or Mlklrescued epithelial cell death and lethality of Casp8∆IECmice, demonstrating the crucial role of Caspase-8 as a negative regulator of necroptosis. While Casp8∆IECTnfr1−/−mice showed improved survival after infection, tissue destruction was similar to Casp8∆IECmice, indicating that necroptosis partially depends on TNF-α signaling. Although there was no impairment in antimicrobial peptide secretion during the early phase of infection, functional Caspase-8 seems to be required to control pathogen colonization. Collectively, these results demonstrate that Caspase-8 is essential to prevent SalmonellaTyphimurium induced enteritis and to ensure host survival by two different mechanisms: maintenance of intestinal barrier function and restriction of pathogen colonization.

Published
2018
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25. PGAM5-mediated programmed necrosis of hepatocytes drives acute liver injury

Author

He, Gui-Wei, Gunther, Claudia, Kremer, Andreas E, Thonn, Veronika, Amann, Kerstin, Poremba, Christopher, Neurath, Markus F, Wirtz, Stefan, and Becker, Christoph

Abstract

ObjectivesAutoimmune hepatitis (AIH) is a severe necroinflammatory liver disease associated with significant mortality. Although loss of hepatocytes is generally recognised as a key trigger of liver inflammation and liver failure, the regulation of hepatic cell death causing AIH remains poorly understood. The aim of this study was to identify molecular mechanisms that drive hepatocyte cell death in the pathogenesis of acute liver injury.DesignAcute liver injury was modelled in mice by intravenous administration of concanavalin A (ConA). Liver injury was demonstrated by serum transaminases and histological assessment of liver sections. PGAM5-deficient mice (PGAM5−/−) were used to determine its role in experimental hepatitis. Mdivi-1 was used as an inhibitor of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Mitochondrial fission and the expression of PGAM5 were compared between liver biopsies derived from patients with AIH and control patients.ResultsPGAM5 was highly expressed in hepatocytes of patients with AIH and in mice with ConA-induced experimental hepatitis. Deficiency of PGAM5 protected mice from ConA-induced hepatocellular death and liver injury. PGAM5 regulated ConA-induced mitochondrial fission in hepatocytes. Administration of the Drp1-inhibitor Mdivi-1 blocked mitochondrial fission, diminished hepatocyte cell death and attenuated liver tissue damage induced by ConA.ConclusionsOur data demonstrate for the first time that PGAM5 plays an indispensable role in the pathogenesis of ConA-induced liver injury. Downstream of PGAM5, Drp1-mediated mitochondrial fission is an obligatory step that drives the execution of hepatic necrosis and tissue damage. Our data highlight the PGAM5-Drp1 axis as a potential therapeutic target for acute immune-mediated liver injury.

Published
2017
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28. Caspase-8 controls the gut response to microbial challenges by Tnf-α-dependent and independent pathways

Author

Günther, Claudia, Buchen, Barbara, He, Gui-Wei, Hornef, Mathias, Torow, Natalia, Neumann, Helmut, Wittkopf, Nadine, Martini, Eva, Basic, Marijana, Bleich, André, Watson, Alastair J. M., Neurath, Markus F., and Becker, Christoph

Subjects
3. Good health
Abstract

Gut : an international journal of gastroenterology and hepatology 64(4), 601-610 (2015). doi:10.1136/gutjnl-2014-307226, Published by MDPI, Basel

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