CARDYADS SIGNED
Controlling Cardiomyocyte Dyadic Structure
Total Cost €
0EC-Contrib. €
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Project "CARDYADS" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITETET I OSLO
Organization address contact info |
| Coordinator Country | Norway [NO] |
| Total cost | 2˙000˙000 € |
| EC max contribution | 2˙000˙000 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-CoG |
| Funding Scheme | ERC-COG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-07-01 to 2020-06-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITETET I OSLO | NO (OSLO) | coordinator | 2˙000˙000.00 |
Map
Project objective
Contraction and relaxation of cardiac myocytes, and thus the whole heart, are critically dependent on dyads. These functional junctions between t-tubules, which are invaginations of the surface membrane, and the sarcoplasmic reticulum allow efficient control of calcium release into the cytosol, and also its removal. Dyads are formed gradually during development and break down during disease. However, the precise nature of dyadic structure is unclear, even in healthy adult cardiac myocytes, as are the triggers and consequences of altering dyadic integrity. In this proposal, my group will investigate the precise 3-dimensional arrangement of dyads and their proteins during development, adulthood, and heart failure by employing CLEM imaging (PALM and EM tomography). This will be accomplished by developing transgenic mice with fluorescent labels on four dyadic proteins (L-type calcium channel, ryanodine receptor, sodium-calcium exchanger, SERCA), and by imaging tissue from explanted normal and failing human hearts. The signals responsible for controlling dyadic formation, maintenance, and disruption will be determined by performing high-throughput sequencing to identify novel genes involved with these processes in several established model systems. Particular focus will be given to investigating left ventricular wall stress and stretch-dependent gene regulation as controllers of dyadic integrity. Candidate genes will be manipulated in cell models and transgenic animals to promote dyadic formation and maintenance, and reverse dyadic disruption in heart failure. The consequences of dyadic structure for function will be tested experimentally and with mathematical modeling to examine effects on cardiac myocyte calcium homeostasis and whole-heart function. The results of this project are anticipated to yield unprecedented insight into dyadic structure, regulation, and function, and to identify novel therapeutic targets for heart disease patients.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
D. B. Lipsett, M. Frisk, J. M. Aronsen, E. S. Nordén, O. R. Buonarati, A. Cataliotti, J. W. Hell, I. Sjaastad, G. Christensen, W. E. Louch Cardiomyocyte substructure reverts to an immature phenotype during heart failure published pages: 1833-1853, ISSN: 0022-3751, DOI: 10.1113/jp277273 |
The Journal of Physiology 597/7 | 2020-03-05 |
| 2018 |
Kylie S. Foo, Miia L. Lehtinen, Chuen Yan Leung, Xiaojun Lian, Jiejia Xu, Wendy Keung, Lin Geng, Terje R.S. Kolstad, Sebastian Thams, Andy On-tik Wong, Nicodemus Wong, Kristine Bylund, Chikai Zhou, Xiaobing He, Shao-Bo Jin, Jonathan Clarke, Urban Lendahl, Ronald A. Li, William E. Louch, Kenneth R. Chien Human ISL1 + Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post Infarction published pages: 1644-1659, ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2018.02.012 |
Molecular Therapy 26/7 | 2020-03-05 |
| 2019 |
William E. Louch Channel surfing: new insights into plasticity of excitationâ€contraction coupling published pages: 2119-2120, ISSN: 0022-3751, DOI: 10.1113/jp277783 |
The Journal of Physiology 597/8 | 2020-03-05 |
| 2018 |
Xin Shen, Jonas den Brink, Yufeng Hou, Dylan Colli, Christopher Le, Terje R. Kolstad, Niall MacQuaide, Cathrine R. Carlson, Peter M. Kekenesâ€Huskey, Andrew G. Edwards, Christian Soeller, William E. Louch 3D dSTORM imaging reveals novel detail of ryanodine receptor localization in rat cardiac myocytes published pages: 399-418, ISSN: 0022-3751, DOI: 10.1113/JP277360 |
The Journal of Physiology 597/2 | 2020-03-05 |
| 2018 |
Åsmund T Røe, Marianne Ruud, Emil K Espe, Ornella Manfra, Stefano Longobardi, Jan M Aronsen, Einar Sjaastad Nordén, Trygve Husebye, Terje R S Kolstad, Alessandro Cataliotti, Geir Christensen, Ole M Sejersted, Steven A Niederer, Geir Øystein Andersen, Ivar Sjaastad, William E Louch Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression published pages: 752-764, ISSN: 0008-6363, DOI: 10.1093/cvr/cvy257 |
Cardiovascular Research 115/4 | 2020-03-05 |
| 2019 |
Anett H. Ottesen, Cathrine R. Carlson, Olav Søvik Eken, Mani Sadredini, Peder L. Myhre, Xin Shen, Bjørn Dalhus, Derek R. Laver, Per Kristian Lunde, Jouni Kurola, Marianne Lunde, Jon Erik Hoff, Kristin Godang, Ivar Sjaastad, Ville Pettilä, Mats Stridsberg, Stephan E. Lehnart, Andrew G. Edwards, Ida G. Lunde, Torbjørn Omland, Mathis K. Stokke, Geir Christensen, Helge Røsjø, William E. Louch Secretoneurin Is an Endogenous Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor That Attenuates Ca 2+ -Dependent Arrhythmia published pages: , ISSN: 1941-3149, DOI: 10.1161/CIRCEP.118.007045 |
Circulation: Arrhythmia and Electrophysiology 12/4 | 2020-03-05 |
| 2019 |
Martin Laasmaa, Pengfei Lu, Mladen Veletić, William E. Louch, Jacob Bergsland, Ilangko Balasingham, Marko Vendelin Energy-efficiency of Cardiomyocyte Stimulation with Rectangular Pulses published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-49791-w |
Scientific Reports 9/1 | 2020-03-05 |
| 2018 |
Peter P. Jones, Niall MacQuaide, William E. Louch Dyadic Plasticity in Cardiomyocytes published pages: , ISSN: 1664-042X, DOI: 10.3389/fphys.2018.01773 |
Frontiers in Physiology 9 | 2020-03-05 |
| 2018 |
Terje R Kolstad, Jonas van den Brink, Niall MacQuaide, Per Kristian Lunde, Michael Frisk, Jan Magnus Aronsen, Einar S Norden, Alessandro Cataliotti, Ivar Sjaastad, Ole M Sejersted, Andrew G Edwards, Glenn Terje Lines, William E Louch Ryanodine receptor dispersion disrupts Ca2+ release in failing cardiac myocytes published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.39427 |
eLife 7 | 2020-03-05 |
| 2017 |
Ornella Manfra, Michael Frisk, William E. Louch Regulation of Cardiomyocyte T-Tubular Structure: Opportunities for Therapy published pages: 167-178, ISSN: 1546-9530, DOI: 10.1007/s11897-017-0329-9 |
Current Heart Failure Reports 14/3 | 2019-06-06 |
| 2017 |
Mary M Maleckar, Andrew G Edwards, William E Louch, Glenn T Lines Studying dyadic structure–function relationships: a review of current modeling approaches and new insights into Ca 2+ (mis)handling published pages: 117954681769860, ISSN: 1179-5468, DOI: 10.1177/1179546817698602 |
Clinical Medicine Insights: Cardiology 11 | 2019-06-06 |
| 2017 |
Shan S. Parikh, Daniel J. Blackwell, Nieves Gomez-Hurtado, Michael Frisk, Lili Wang, Kyungsoo Kim, Christen P. Dahl, Arnt Fiane, Theis Tønnessen, Dmytro O. Kryshtal, William E. Louch, Bjorn C. Knollmann Thyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell–Derived CardiomyocytesNovelty and Significance published pages: 1323-1330, ISSN: 0009-7330, DOI: 10.1161/CIRCRESAHA.117.311920 |
Circulation Research 121/12 | 2019-06-06 |
| 2017 |
Åsmund T. Røe, Jan Magnus Aronsen, Kristine Skårdal, Nazha Hamdani, Wolfgang A. Linke, Håvard E. Danielsen, Ole M. Sejersted, Ivar Sjaastad, William E. Louch Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy published pages: 1161-1172, ISSN: 0008-6363, DOI: 10.1093/cvr/cvx087 |
Cardiovascular Research 113/10 | 2019-06-06 |
| 2016 |
Michael Frisk, Marianne Ruud, Emil K. S. Espe, Jan Magnus Aronsen, Åsmund T. Røe, Lili Zhang, Per Andreas Norseng, Ole M. Sejersted, Geir A. Christensen, Ivar Sjaastad, William E. Louch Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis published pages: 443-451, ISSN: 0008-6363, DOI: 10.1093/cvr/cvw111 |
Cardiovascular Research 112/1 | 2019-06-06 |
| 2017 |
William E. Louch, Stanley Nattel T-tubular collagen: a new player in mechanosensing and disease? published pages: 839-840, ISSN: 0008-6363, DOI: 10.1093/cvr/cvx091 |
Cardiovascular Research 113/8 | 2019-06-06 |
| 2017 |
Sara Gattoni, Åsmund Treu Røe, Jan Magnus Aronsen, Ivar Sjaastad, William E. Louch, Nicolas P. Smith, Steven A. Niederer Compensatory and decompensatory alterations in cardiomyocyte Ca 2+ dynamics in hearts with diastolic dysfunction following aortic banding published pages: 3867-3889, ISSN: 0022-3751, DOI: 10.1113/JP273879 |
The Journal of Physiology 595/12 | 2019-06-06 |
| 2017 |
Andrew G Edwards, William E Louch Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus published pages: 117954681668606, ISSN: 1179-5468, DOI: 10.1177/1179546816686061 |
Clinical Medicine Insights: Cardiology 11 | 2019-06-06 |
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