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STEMCARDIORISK SIGNED

Stem Cells for Cardiac Arrhythmia Risk Assessment

Total Cost €

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EC-Contrib. €

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Partnership

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 STEMCARDIORISK project word cloud

Explore the words cloud of the STEMCARDIORISK project. It provides you a very rough idea of what is the project "STEMCARDIORISK" about.

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Project "STEMCARDIORISK" data sheet

The following table provides information about the project.

Coordinator
ACADEMISCH ZIEKENHUIS LEIDEN 

Organization address
address: ALBINUSDREEF 2
city: LEIDEN
postcode: 2333 ZA
website: www.lumc.nl

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 Netherlands [NL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2020-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ACADEMISCH ZIEKENHUIS LEIDEN NL (LEIDEN) coordinator 1˙500˙000.00

Map

 Project objective

Among the most significant conceptual changes in stem cell biology of the past decade has been the use of human pluripotent stem cells (hPSCs) for disease modelling and drug development rather than solely as therapeutics. One area of major interest in this context is that of arrhythmic disorders of the heart. Cardiac arrhythmias are a leading cause of death among young people, with inherited forms affecting as many as 1 in 2000. Even more prevalent are acquired arrhythmias due to adverse responses to medication. These too have a significant heritable component. Although hundreds of mutations have been associated with both forms of arrhythmia, two outstanding issues remain: (i) it is difficult to prove the identified mutation is causal, and (ii) large differences in disease severity are seen even among patients with the same primary mutation. To date hPSC models of arrhythmogenic diseases exhibit the characteristic electrophysiological features of the respective disorders; however lack of appropriate controls and inherent variability between hPSC lines means that it is still unclear how well these models reflect the genotype-phenotype relationship. This proposal will combine hPSC disease modelling with recent advances in gene-editing, plus the wealth of genomic data associating genetic variants to disease phenotypes, to develop unique approaches that will 1) establish the sensitivity of these models and; 2) provide more accurate functional assessment of the contribution of individual variants to congenital and acquired arrhythmias. I believe that by creating panels of isogenic PSC lines differing exclusively at candidate genetic loci we can (i) predict the pathogenicity of variants; (ii) shed light on the mechanism underlying the disease phenotype, and (iii) improve individual risk stratification and patient-specific pharmacotherapy. This study will also offer a first entry into interpreting GWAS and capitalising on the value of the human genome sequencing projects.

 Publications

year authors and title journal last update
List of publications.
2018 David J. Anderson, David I. Kaplan, Katrina M. Bell, Katerina Koutsis, John M. Haynes, Richard J. Mills, Dean G. Phelan, Elizabeth L. Qian, Ana Rita Leitoguinho, Deevina Arasaratnam, Tanya Labonne, Elizabeth S. Ng, Richard P. Davis, Simona Casini, Robert Passier, James E. Hudson, Enzo R. Porrello, Mauro W. Costa, Arash Rafii, Clare L. Curl, Lea M. Delbridge, Richard P. Harvey, Alicia Oshlack, Michael M. Cheung, Christine L. Mummery, Stephen Petrou, Andrew G. Elefanty, Edouard G. Stanley, David A. Elliott
NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-03714-x
Nature Communications 9/1 2019-05-29
2017 Karina O. Brandão, Viola A. Tabel, Douwe E. Atsma, Christine L. Mummery, Richard P. Davis
Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies
published pages: 1039-1059, ISSN: 1754-8403, DOI: 10.1242/dmm.030320
Disease Models & Mechanisms 10/9 2019-05-29
2017 Verena Schwach, Arie O. Verkerk, Mervyn Mol, Jantine J. Monshouwer-Kloots, Harsha D. Devalla, Valeria V. Orlova, Konstantinos Anastassiadis, Christine L. Mummery, Richard P. Davis, Robert Passier
A COUP-TFII Human Embryonic Stem Cell Reporter Line to Identify and Select Atrial Cardiomyocytes
published pages: 1765-1779, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2017.10.024
Stem Cell Reports 9/6 2019-05-29
2018 Luca Sala, Berend J. van Meer, Leon G.J. Tertoolen, Jeroen Bakkers, Milena Bellin, Richard P. Davis, Chris Denning, Michel A.E. Dieben, Thomas Eschenhagen, Elisa Giacomelli, Catarina Grandela, Arne Hansen, Eduard R. Holman, Monique R.M. Jongbloed, Sarah M. Kamel, Charlotte D. Koopman, Quentin Lachaud, Ingra Mannhardt, Mervyn P.H. Mol, Diogo Mosqueira, Valeria V. Orlova, Robert Passier, Marcelo C. Ribeiro, Umber Saleem, Godfrey L. Smith, Francis L. Burton, Christine L. Mummery
MUSCLEMOTIONNovelty and Significance
published pages: e5-e16, ISSN: 0009-7330, DOI: 10.1161/CIRCRESAHA.117.312067
Circulation Research 122/3 2019-05-29

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