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1. A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery

Author

Emilie Crouchet, Simonetta Bandiera, Naoto Fujiwara, Shen Li, Hussein El Saghire, Mirian Fernández-Vaquero, Tobias Riedl, Xiaochen Sun, Hadassa Hirschfield, Frank Jühling, Shijia Zhu, Natascha Roehlen, Clara Ponsolles, Laura Heydmann, Antonio Saviano, Tongqi Qian, Anu Venkatesh, Joachim Lupberger, Eloi R. Verrier, Mozhdeh Sojoodi, Marine A. Oudot, François H. T. Duong, Ricard Masia, Lan Wei, Christine Thumann, Sarah C. Durand, Victor González-Motos, Danijela Heide, Jenny Hetzer, Shigeki Nakagawa, Atsushi Ono, Won-Min Song, Takaaki Higashi, Roberto Sanchez, Rosa S. Kim, C. Billie Bian, Karun Kiani, Tom Croonenborghs, Aravind Subramanian, Raymond T. Chung, Beate K. Straub, Detlef Schuppan, Maliki Ankavay, Laurence Cocquerel, Evelyne Schaeffer, Nicolas Goossens, Anna P. Koh, Milind Mahajan, Venugopalan D. Nair, Ganesh Gunasekaran, Myron E. Schwartz, Nabeel Bardeesy, Alex K. Shalek, Orit Rozenblatt-Rosen, Aviv Regev, Emanuele Felli, Patrick Pessaux, Kenneth K. Tanabe, Mathias Heikenwälder, Catherine Schuster, Nathalie Pochet, Mirjam B. Zeisel, Bryan C. Fuchs, Yujin Hoshida, and Thomas F. Baumert

Subjects
Science
Abstract

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

Published
2021
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2. Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes

Author

Eloi R. Verrier, Che C. Colpitts, Charlotte Bach, Laura Heydmann, Laetitia Zona, Fei Xiao, Christine Thumann, Emilie Crouchet, Raphaël Gaudin, Camille Sureau, François-Loïc Cosset, Jane A. McKeating, Patrick Pessaux, Yujin Hoshida, Catherine Schuster, Mirjam B. Zeisel, and Thomas F. Baumert

Subjects
Biology (General), QH301-705.5
Abstract

Summary: Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies. : Verrier et al. identify the sodium taurocholate co-transporter NTCP as a host factor regulating HCV infection. NTCP-mediated bile acid transport regulates innate responses targeting HCV infection. NTCP is a mediator of innate immunity and plays a role in the infection of multiple hepatotropic viruses. Keywords: NTCP, hepatitis C virus, solute carrier, innate immune responses, viral entry, host factor, signaling, antiviral therapy, hepatitis B virus, hepatitis D virus

Published
2016
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3. Treatment of HCC with claudin-1-specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment

Author

Natascha Roehlen, Marion Muller, Zeina Nehme, Emilie Crouchet, Frank Jühling, Fabio Del Zompo, Sara Cherradi, Francois H.T. Duong, Nuno Almeida, Antonio Saviano, Mirian Fernández-Vaquero, Tobias Riedl, Houssein El Saghire, Sarah C. Durand, Clara Ponsolles, Marine A. Oudot, Romain Martin, Nicolas Brignon, Emanuele Felli, Patrick Pessaux, Antonin Lallement, Irwin Davidson, Simonetta Bandiera, Christine Thumann, Patrice Marchand, Solange Moll, Brandon Nicolay, Nabeel Bardeesy, Yujin Hoshida, Mathias Heikenwälder, Roberto Iacone, Alberto Toso, Markus Meyer, Greg Elson, Tamas Schweighoffer, Geoffrey Teixeira, Mirjam B. Zeisel, Patrice Laquerriere, Joachim Lupberger, Catherine Schuster, Laurent Mailly, Thomas F. Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nouvel Hôpital Civil de Strasbourg, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre médical universitaire de Genève (CMU), Harvard Medical School [Boston] (HMS), University of Texas Southwestern Medical Center, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)

Subjects
tumor immune microenvironment, Hepatology, tight junction, Aucun, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, resistance, stemness, pharmacology, therapeutic use, CLDN1, plasticity, genetics, HCC, Liver cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Despite recent approvals, the response to treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) remain poor. Claudin-1 (CLDN1) is a membrane protein that is expressed at tight junctions, but it can also be exposed non-junctionally, such as on the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored. Using humanized monoclonal antibodies (mAbs) specifically targeting the extracellular loop of human non-junctional CLDN1 and a large series of patient-derived cell-based and animal model systems we aimed to investigate the role of CLDN1 as a therapeutic target for HCC. Targeting non-junctional CLDN1 markedly suppressed tumor growth and invasion in cell line-based models of HCC and patient-derived 3D ex vivo models. Moreover, the robust effect on tumor growth was confirmed in vivo in a large series of cell line-derived xenograft and patient-derived xenograft mouse models. Mechanistic studies, including single-cell RNA sequencing of multicellular patient HCC tumorspheres, suggested that CLDN1 regulates tumor stemness, metabolism, oncogenic signaling and perturbs the tumor immune microenvironment. Our results provide the rationale for targeting CLDN1 in HCC and pave the way for the clinical development of CLDN1-specific mAbs for the treatment of advanced HCC. Hepatocellular carcinoma (HCC) is associated with high mortality and unsatisfactory treatment options. Herein, we identified the cell surface protein Claudin-1 as a treatment target for advanced HCC. Monoclonal antibodies targeting Claudin-1 inhibit tumor growth in patient-derived ex vivo and in vivo models by modulating signaling, cell stemness and the tumor immune microenvironment. Given the differentiated mechanism of action, the identification of Claudin-1 as a novel therapeutic target for HCC provides an opportunity to break the plateau of limited treatment response. The results of this preclinical study pave the way for the clinical development of Claudin-1-specific antibodies for the treatment of advanced HCC. It is therefore of key impact for physicians, scientists and drug developers in the field of liver cancer and gastrointestinal oncology. journal article research support, non-u.s. gov't 2023 Feb 2022 10 27 imported

Published
2023
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4. A monoclonal antibody targeting nonjunctional claudin-1 inhibits fibrosis in patient-derived models by modulating cell plasticity

Author

Natascha Roehlen, Antonio Saviano, Houssein El Saghire, Emilie Crouchet, Zeina Nehme, Fabio Del Zompo, Frank Jühling, Marine A. Oudot, Sarah C. Durand, François H. T. Duong, Sara Cherradi, Victor Gonzalez Motos, Nuno Almeida, Clara Ponsolles, Laura Heydmann, Tessa Ostyn, Antonin Lallement, Patrick Pessaux, Emanuele Felli, Andrea Cavalli, Jacopo Sgrignani, Christine Thumann, Olga Koutsopoulos, Bryan C. Fuchs, Yujin Hoshida, Maike Hofmann, Mogens Vyberg, Birgitte Martine Viuff, Elisabeth D. Galsgaard, Greg Elson, Alberto Toso, Markus Meyer, Roberto Iacone, Tamas Schweighoffer, Geoffrey Teixeira, Solange Moll, Claudio De Vito, Tania Roskams, Irwin Davidson, Danijela Heide, Mathias Heikenwälder, Mirjam B. Zeisel, Joachim Lupberger, Laurent Mailly, Catherine Schuster, and Thomas F. Baumert

Subjects
Liver Cirrhosis, Mice, Claudin-1, Cell Plasticity, Antibodies, Monoclonal, Animals, Humans, General Medicine, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Antibodies, Monoclonal/pharmacology, Liver Cirrhosis/drug therapy
Abstract

Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family. Although the role of CLDN1 incorporated in tight junctions is well established, the function of nonjunctional CLDN1 (njCLDN1) is largely unknown. Using highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed njCLDN1, we show in patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models that CLDN1 is a mediator and target for liver fibrosis. Targeting CLDN1 reverted inflammation-induced hepatocyte profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies of a fully humanized antibody in nonhuman primates did not reveal any serious adverse events even at high steady-state concentrations. Our results provide preclinical proof of concept for CLDN1-specific monoclonal antibodies for the treatment of advanced liver fibrosis and cancer prevention. Antifibrotic effects in lung and kidney fibrosis models further indicate a role of CLDN1 as a therapeutic target for tissue fibrosis across organs. In conclusion, our data pave the way for further therapeutic exploration of CLDN1-targeting therapies for fibrotic diseases in patients.

Published
2022
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5. In vivo loss-of-function studies unravel protein tyrosine phosphatase delta as a regulator of liver regeneration during metabolic liver disease

Author

Armando Andres Roca Suarez, Laurent Mailly, Natascha Roehlen, Alessia Virzi, Nicolas Brignon, Frank Jühling, Christine Thumann, Sarah Durand, Marine Oudot, Eugénie Schaeffer, Romain Martin, Laura Heydmann, Charlotte Bach, Romain Parent, Carole Jamey, Daniel Brumaru, Nassim Dali-Youcef, Emanuele Felli, Patrick Pessaux, Atish Mukherji, Catherine Schuster, Thomas Baumert, and Joachim Lupberger

Subjects
Hepatology
Published
2022
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6. Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma

Author

Frank Jühling, Nourdine Hamdane, Emilie Crouchet, Shen Li, Hussein El Saghire, Atish Mukherji, Christine Thumann, Marine Oudot, Antonio Saviano, Armando Andres Roca Suarez, Ricard Masia, Mozhdeh Sojoodi, Gunisha Arora, Atsushi Ono, Parissa Tabrizian, Myron Schwartz, Irwin Davidson, Christian Schmidl, Christoph Bock, Catherine Schuster, Kazuaki Chayama, Patrick Pessaux, Kenneth K. Tanabe, Yujin Hoshida, Mirjam Zeisel, François H.T. Duong, Bryan Fuchs, and Thomas Baumert

Subjects
Hepatology
Published
2020
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7. A human liver cell-based system modeling a clinical prognostic liver signature combined with single cell RNA-seq for discovery of novel liver disease therapeutics

Author

Emilie Crouchet, Simonetta Bandiera, Naoto Fujiwara, Shen Li, Hussein El Saghire, Xiaochen Sun, Hadassa Hirschfield, Natascha Roehlen, Frank Jühling, Antonio Saviano, Victor Gonzalez-Motos, Anu Venkatesh, Clara Ponsolles, Eloi Verrier, Nicolaas Van Renne, Joachim Lupberger, Christine Thumann, François H.T. Duong, Shijia Zhu, Mozhdeh Sojoodi, Ricard Masia, Lan Wei, Marine Oudot, Sarah Durand, Shigeki Nakagawa, Atsushi Ono, Won-Min Song, Takaaki Higashi, Roberto Sanchez, Rosa S. Kim, C. Billie Bian, Karun Kiani, Tom Croonenborghs, Aravind Subramanian, Raymond Chung, Danijela Heide, Jenny Hetzer, Beate Straub, Detlef Schuppan, Maliki Ankavay, Laurence Cocquerel, Evelyne Schaeffer, Nicolas Goossens, Anna P. Koh, Milind Mahajan, Venugopalan D. Nair, Ganesh Gunasekaran, Myron Schwartz, Nabeel Bardeesy, Alex K. Shalek, Orit Rozenblatt-Rosen, Aviv Regev, Mathias Heikenwalder, Emanuele Felli, Patrick Pessaux, Kenneth K. Tanabe, Catherine Schuster, Nathalie Pochet, Mirjam Zeisel, Bryan C. Fuchs, Yujin Hoshida, and Thomas Baumert

Subjects
Hepatology
Published
2020
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8. HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response

Author

Nourdine Hamdane, Frank Jühling, Emilie Crouchet, Houssein El Saghire, Christine Thumann, Marine A. Oudot, Simonetta Bandiera, Antonio Saviano, Clara Ponsolles, Armando Andres Roca Suarez, Shen Li, Naoto Fujiwara, Atsushi Ono, Irwin Davidson, Nabeel Bardeesy, Christian Schmidl, Christoph Bock, Catherine Schuster, Joachim Lupberger, François Habersetzer, Michel Doffoël, Tullio Piardi, and Daniele So

Published
2019
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9. Clearance of persistent hepatitis C virus infection using a claudin-1-targeting monoclonal antibody

Author

Christopher J. Mee, Markus H. Heim, Patrick Pessaux, Erika Girardi, Sébastien Pfeffer, Christopher Davis, Simonetta Bandiera, Isabel Fofana, Ralf Bartenschlager, Lars Kaderali, Koen Vercauteren, Diego Calabrese, Laurent Mailly, Céline Leboeuf, Nicola F. Fletcher, Maura Dandri, Pascal Villa, Helen J. Harris, Tassilo Volz, Mirjam B. Zeisel, Fei Xiao, Michel Neunlist, Eric Robinet, Marc Lütgehetmann, Béatrice Chane-Woon-Ming, Philip Meuleman, Jane A. McKeating, Thomas F. Baumert, Maria Ericsson, Joachim Lupberger, Garrick K. Wilson, Francois H.T. Duong, Philippe Aubert, Christine Thumann, univOAK, Archive ouverte, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de chimie biologique intégrative de Strasbourg (PCBiS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
Liver Cirrhosis, medicine.drug_class, Hepatitis C virus, Biomedical Engineering, Bioengineering, Hepacivirus, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Monoclonal antibody, medicine.disease_cause, Antibodies, Monoclonal, Humanized, Applied Microbiology and Biotechnology, Article, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Claudin-1, medicine, Animals, Humans, biology, Virus receptor, Antibodies, Monoclonal, Hepatitis C, medicine.disease, Virology, 3. Good health, Chronic infection, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Monoclonal, Immunology, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Hepatocytes, Molecular Medicine, Antibody, Biotechnology, CD81
Abstract

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer. Cell entry of HCV and other pathogens is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model, we show that a monoclonal antibody specific for the TJ protein claudin-1 (ref. 7) eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection by means of host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy. INTERREG-IV-Rhin Supérieur-FEDER-Hepato-Regio-Net 2009 and 2012

Published
2015
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10. Humanisation of a claudin-1-specific monoclonal antibody for clinical prevention and cure of HCV infection without escape

Author

Che C Colpitts, Rajiv G Tawar, Laurent Mailly, Christine Thumann, Laura Heydmann, Sarah C Durand, Fei Xiao, Eric Robinet, Patrick Pessaux, Mirjam B Zeisel, Thomas F Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle hépato-digestif [Strasbourg], Nouvel Hôpital Civil, Hospices Civils de Strasbourg-Institut Hospitalo-Universitaire de strasbourg, This study was supported by funding from the European Union (FP7 HEPAMAB GAN 305600, ERC-2014-AdG-HEPCIR, EU H2020 HEPCAR and Interreg IV-Rhin Supérieur-FEDER-Hepato-Regio-Net 2012), the Agence Nationale de Recherche sur le SIDA (ANRS) (2012/318, 2013/108) the Direction Générale de l’Offre de Soins (A12027MS) and the US National Institutes of Health (1U19AI123862-01). This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and benefits from funding from the state managed by the French National Research Agency as part of the Investments for the Future programme. CCC is supported by fellowships from the Canadian Institutes of Health Research (201411MFE-338606-245517) and the Canadian Network on Hepatitis C., ANR-10-IDEX-0002,UNISTRA,Functional genomics of viral hepatitis and liver disease(2010), European Project: 305600,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HEPAMAB(2013), European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), daulny, anne, Initiative d'excellence - Par-delà les frontières, l'Université de Strasbourg - - UNISTRA2010 - ANR-10-IDEX-0002 - IDEX - VALID, Human monoclonal antibody therapy to prevent hepatitis C virus reinfection of liver transplants: advancing lead monoclonal antibodies into clinical trial - HEPAMAB - - EC:FP7:HEALTH2013-01-01 - 2017-12-31 - 305600 - VALID, Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID, and ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010)

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, Aucun, Antibodies, Monoclonal, Hepacivirus, Mice, SCID, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, ANTIVIRAL THERAPY, Antiviral Agents, Hepatitis C, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Mice, Treatment Outcome, TIGHT JUNCTION, Claudin-1, Hepatocytes, Animals, Humans, Immunologic Factors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; OBJECTIVE:HCV infection is a leading cause of chronic liver disease and a major indication for liver transplantation. Although direct-acting antivirals (DAAs) have much improved the treatment of chronic HCV infection, alternative strategies are needed for patients with treatment failure. As an essential HCV entry factor, the tight junction protein claudin-1 (CLDN1) is a promising antiviral target. However, genotype-dependent escape via CLDN6 and CLDN9 has been described in some cell lines as a possible limitation facing CLDN1-targeted therapies. Here, we evaluated the clinical potential of therapeutic strategies targeting CLDN1.DESIGN:We generated a humanised anti-CLDN1 monoclonal antibody (mAb) (H3L3) suitable for clinical development and characterised its anti-HCV activity using cell culture models, a large panel of primary human hepatocytes (PHH) from 12 different donors, and human liver chimeric mice.RESULTS:H3L3 pan-genotypically inhibited HCV pseudoparticle entry into PHH, irrespective of donor. Escape was likely precluded by low surface expression of CLDN6 and CLDN9 on PHH. Co-treatment of a panel of PHH with a CLDN6-specific mAb did not enhance the antiviral effect of H3L3, confirming that CLDN6 does not function as an entry factor in PHH from multiple donors. H3L3 also inhibited DAA-resistant strains of HCV and synergised with current DAAs. Finally, H3L3 cured persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy.CONCLUSIONS:Overall, these findings underscore the clinical potential of CLDN1-targeted therapies and describe the functional characterisation of a humanised anti-CLDN1 antibody suitable for further clinical development to complement existing therapeutic strategies for HCV.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Published
2016
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11. In vivo knockdown of Plk1 using a novel breakable mesoporous silica particle siRNA carrier reduces tumor growth in an orthotopic xenograft mouse model of hepatocellular carcinoma

Author

Eric Robinet, Antonio Saviano, Christine Thumann, G.B. About, T.F. Baumert, Francois H.T. Duong, M. Dentinger, T. Sorg-Guss, and L.D. Cola

Subjects
Gene knockdown, Hepatology, Chemistry, In vivo, Hepatocellular carcinoma, Cancer research, medicine, Particle, Tumor growth, Mesoporous silica, medicine.disease, PLK1
Published
2018
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13. Hepatitis C virus-induced epigenetic and transcriptional changes persist post cure

Author

Christoph Bock, Frank Jühling, Yujin Hoshida, Nabeel Bardeesy, François Habersetzer, Simonetta Bandiera, Sarah C. Durand, Patrick Pessaux, T.F. Baumert, Irwin Davidson, Houssein El Saghire, Christine Thumann, Christian Schmidl, Nourdine Hamdane, and Mirjam B. Zeisel

Subjects
030505 public health, Hepatology, business.industry, Hepatitis C virus, Post cure, medicine.disease_cause, Virology, 03 medical and health sciences, 0302 clinical medicine, medicine, 030212 general & internal medicine, Epigenetics, 0305 other medical science, business
Published
2017
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14. Spatiotemporal functional genomics uncovers cell circuits triggering liver disease biology of hepatitis C virus infection

Author

K. Kiani, T.F. Baumert, Steven A. Carr, N. Van Renne, Marko Jovanovic, Joachim Lupberger, Nabeel Bardeesy, Mirjam B. Zeisel, Tom Croonenborghs, Yujin Hoshida, Simonetta Bandiera, Philipp Mertins, James A. Kozubek, A. Regev, H.E. Sagire, Christine Thumann, and Nathalie Pochet

Subjects
Liver disease, medicine.anatomical_structure, Hepatology, Hepatitis C virus, Cell, medicine, Biology, medicine.disease_cause, medicine.disease, Functional genomics, Virology
Published
2017
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15. MIR-146A-5P, A Proviral Factor Up-Regulated by Hepatitis C Virus Infection, Deregulates Metabolic Pathways Relevant for Liver Disease Progression in Hepatocytes

Author

Emilie Crouchet, Tao Ye, Christine Thumann, H. El Saghire, Mirjam B. Zeisel, Sophie Pernot, Simonetta Bandiera, Markus H. Heim, T.F. Baumert, Sarah C. Durand, I. Fofana, and Catherine Schuster

Subjects
Liver disease, Metabolic pathway, Hepatology, Downregulation and upregulation, Hepatitis C virus, medicine, Biology, medicine.disease, medicine.disease_cause, Virology
Published
2016
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17. The Sodium Taurocholate Co-Transporting Polypeptide (NTCP) Facilitates HCV Entry by Modulating Bile Acid Transport and Expression of Interferon-Stimulated Genes

Author

Eloi R. Verrier, T.F. Baumert, Rajiv G. Tawar, Yujin Hoshida, Che C. Colpitts, Laetitia Zona, Camille Sureau, Christine Thumann, Mirjam B. Zeisel, C. Batch, Catherine Schuster, and Laura Heydmann

Subjects
Bile acid transport, Hepatology, Biochemistry, Interferon, Chemistry, Sodium taurocholate, medicine, Gene, medicine.drug
Published
2016
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18. P0676 : Clearance of persistent hepatitis c virus infection using a monoclonal antibody specific for tight junction protein claudin-1

Author

Simonetta Bandiera, Jane A. McKeating, Philip Meuleman, Maura Dandri, Eric Robinet, Diego Calabrese, Patrick Pessaux, Markus H. Heim, Michel Neunlist, Christopher Davis, Isabel Fofana, Francois H.T. Duong, Laurent Mailly, Philippe Aubert, Lars Kaderali, Garrick K. Wilson, Céline Leboeuf, Marc Lütgehetmann, Nicola F. Fletcher, Helen J. Harris, Christine Thumann, Béatrice Chane-Woon-Ming, Pascal Villa, Joachim Lupberger, Christopher J. Mee, Sébastien Pfeffer, Koen Vercauteren, Ralf Bartenschlager, Mirjam B. Zeisel, Fei Xiao, Erika Girardi, Tassilo Volz, Thomas F. Baumert, and Maria Ericsson

Subjects
Hepatology, Tight junction, medicine.drug_class, Hepatitis C virus, medicine, Biology, Monoclonal antibody, Claudin, medicine.disease_cause, Virology
Published
2015
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