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New Chol SIGNED

Development of New therapies against cholangiopathies.

Total Cost €

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EC-Contrib. €

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Partnership

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Project "New Chol" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 2˙499˙111 €
 EC max contribution 2˙499˙111 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-12-01   to  2022-11-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 2˙499˙111.00

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 Project objective

Cholangiopathies represent a diverse group of diseases affecting cholangiocytes which are the main cell type of the biliary tract. These disorders range from inherited (Cystic Fibrosis) and developmental (Alagille Syndrome, Biliary Atresia) to autoimmune (Primary Biliary Cirrhosis), idiopathic (Primary Sclerosing Cholangitis) and drug or toxin induced diseases. Cholangiopathies result in toxic bile accumulation in the liver inducing cell death and ultimately cirrhosis. They carry high morbidity and mortality, accounting for up to a third of chronic liver disorders. Whole liver transplantation remains the main treatment. However, organ transplant requires immunosuppression with significant side effects and an increasing number of patients die while on the transplant list due to the shortage of suitable donors. Finally, the absence of physiologically relevant in vitro systems to model and to study cholangiopathies prevents the development of new therapeutics while cell based therapy approach have been unexplored. Here, we propose to systematically address these challenges by developing a novel and innovative program of translational research focusing on cholangiopathies. We will first investigate the cellular and functional diversity of the biliary tract and its impact on disease by taking advantage of recent developments in single cell transcriptomic analyses. We will then use this basic knowledge to generate and to characterize for the first time a renewable source of cholangiocytes from human induced pluripotent stem cells and from biliary tissue. The resulting cells will be used to model cholangiopathies in vitro and to create a new platform for drug target identification. Finally, we will explore the potential for in vitro generated cholangiocytes to be used in regenerative medicine applications including cell based therapy. Overall this comprehensive program will uniquely path the way for the development of a whole range of new therapies for cholangiopathies.

 Publications

year authors and title journal last update
List of publications.
2018 Charis-Patricia Segeritz, Sheikh Tamir Rashid, Miguel Cardoso de Brito, Maria Paola Serra, Adriana Ordonez, Carola Maria Morell, Joseph E. Kaserman, Pedro Madrigal, Nicholas R.F. Hannan, Laurent Gatto, Lu Tan, Andrew A. Wilson, Kathryn Lilley, Stefan J. Marciniak, Bibek Gooptu, David A. Lomas, Ludovic Vallier
hiPSC hepatocyte model demonstrates the role of unfolded protein response and inflammatory networks in α1-antitrypsin deficiency
published pages: 851-860, ISSN: 0168-8278, DOI: 10.1016/j.jhep.2018.05.028
Journal of Hepatology 69/4 2020-01-28
2019 Loukia Yiangou, Rodrigo A. Grandy, Carola M. Morell, Rute A. Tomaz, Anna Osnato, Juned Kadiwala, Daniele Muraro, Jose Garcia-Bernardo, Shota Nakanoh, William G. Bernard, Daniel Ortmann, Davis J. McCarthy, Ingrid Simonic, Sanjay Sinha, Ludovic Vallier
Method to Synchronize Cell Cycle of Human Pluripotent Stem Cells without Affecting Their Fundamental Characteristics
published pages: 165-179, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2018.11.020
Stem Cell Reports 12/1 2020-01-28
2018 Alexander W. Justin, Kourosh Saeb-Parsy, Athina E. Markaki, Ludovic Vallier, Fotios Sampaziotis
Advances in the generation of bioengineered bile ducts
published pages: 1532-1538, ISSN: 0925-4439, DOI: 10.1016/j.bbadis.2017.10.034
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1864/4 2020-01-28
2019 Judith Kraiczy, Alexander D.B. Ross, Jessica L. Forbester, Gordon Dougan, Ludovic Vallier, Matthias Zilbauer
Genome-Wide Epigenetic and Transcriptomic Characterization of Human-Induced Pluripotent Stem Cell–Derived Intestinal Epithelial Organoids
published pages: 285-288, ISSN: 2352-345X, DOI: 10.1016/j.jcmgh.2018.10.008
Cellular and Molecular Gastroenterology and Hepatology 7/2 2020-01-28
2019 Stephanie M. Linker, Lara Urban, Stephen J. Clark, Mariya Chhatriwala, Shradha Amatya, Davis J. McCarthy, Ingo Ebersberger, Ludovic Vallier, Wolf Reik, Oliver Stegle, Marc Jan Bonder
Combined single-cell profiling of expression and DNA methylation reveals splicing regulation and heterogeneity
published pages: , ISSN: 1474-760X, DOI: 10.1186/s13059-019-1644-0
Genome Biology 20/1 2020-01-28
2018 Alessandro Bertero, Stephanie Brown, Pedro Madrigal, Anna Osnato, Daniel Ortmann, Loukia Yiangou, Juned Kadiwala, Nina C. Hubner, Igor Ruiz de los Mozos, Christoph Sadée, An-Sofie Lenaerts, Shota Nakanoh, Rodrigo Grandy, Edward Farnell, Jernej Ule, Hendrik G. Stunnenberg, Sasha Mendjan, Ludovic Vallier
The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency
published pages: 256-259, ISSN: 0028-0836, DOI: 10.1038/nature25784
Nature 555/7695 2020-01-28
2019 Angélique Fourrier, Frédéric Delbos, Séverine Menoret, Camille Collet, Linh Trinh Thi Thuy, Anne Myara, François Petit, Laia Tolosa, Sophie Laplanche, María José Gómez‐Lechón, Philippe Labrune, Ignacio Anegon, Ludovic Vallier, Delphine Garnier, Tuan Huy Nguyen
Regenerative cell therapy for the treatment of hyperbilirubinemic Gunn rats with fresh and frozen human induced pluripotent stem cells‐derived hepatic stem cells
published pages: , ISSN: 0908-665X, DOI: 10.1111/xen.12544
Xenotransplantation 2020-01-28
2018 Loukia Yiangou, Alexander D.B. Ross, Kim Jee Goh, Ludovic Vallier
Human Pluripotent Stem Cell-Derived Endoderm for Modeling Development and Clinical Applications
published pages: 485-499, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.03.016
Cell Stem Cell 22/4 2020-01-28

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