Titin Signals SIGNED
Molecular dissection of titin-based mechanisms in charge of cardiomyocyte dysfunction in terminal feart failure
Total Cost €
0EC-Contrib. €
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Project "Titin Signals" data sheet
The following table provides information about the project.
| Coordinator |
ZENTRALINSTITUT FUER SEELISCHE GESUNDHEIT
Organization address contact info |
| Coordinator Country | Germany [DE] |
| Total cost | 239˙860 € |
| EC max contribution | 239˙860 € (100%) |
| Programme |
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility) |
| Code Call | H2020-MSCA-IF-2014 |
| Funding Scheme | MSCA-IF-GF |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-07-01 to 2019-12-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | ZENTRALINSTITUT FUER SEELISCHE GESUNDHEIT | DE (MANNHEIM) | coordinator | 239˙860.00 |
| 2 | RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG | DE (HEIDELBERG) | participant | 0.00 |
| 3 | THE REGENTS OF THE UNIVERSITY OF CALIFORNIA | US (OAKLAND CA) | partner | 0.00 |
Map
Project objective
Chronic heart failure is a leading cause of mortality in the industrialized countries. Pathomechanistically, a variety of diverse stress signals on the cardiomyocyte trigger loss of myofibrils and cardiomyocyte death, thereby activating a vicious cycle of cardiac stress and deterioration during terminal heart failure. Despite the enormous clinical relevance, the exact pathomechanisms in charge remains unclear.
Here, I propose to investigate the molecular mechanisms that couple mechanical cardiomyocyte strain and cardiomyocyte loss during the heart failure involving the mechanosensing titin filament. For this, I will perform research in three globally leading teams and access their complementary expertise in a secondment scheme. In the the proposed 2-year outgoing phase, I will study how cardioprotection is mediated by key factors recently identified in the Ju Chen lab (UCSD, San Diego). During this time, I will be trained in cutting-edge molecular mouse genetic models and phenotyping tools. This research is expected to shed light on CARP-titinsignaling axis in cardiomyocyte death and to provide tools for manipulating this pathway. In a one-year re-integration phase I will perform follow-up mechanistic structural studies in the Olga Mayans lab (University of Liverpool) to determine the structural basis how the CARP (cardiac ankyrin repeat protein)-titin signaling axis mediates cardiomyocyte protection, and in the Labeit lab (University of Heidelberg, Medical Faculty Mannheim) how to perturb activity of this complex by small molecules.
Taken together, this work encompasses structural studies at the atomic level up to vivo animal models to study CARP-titin functions. After the propose three years, I expect to be ready to pursue an independent career in the field of molecular cardiology research. Therefore, my goal during the re-integration phase will be to set-up an interdisciplinary collaboration involving the three lead teams of this proposal.
Deliverables
| The summary of data generated in first 12 months of project | Open Research Data Pilot | 2019-09-02 09:42:46 |
Take a look to the deliverables list in detail: detailed list of Titin Signals deliverables.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2018 |
Cornelis J Boogerd, Xiaoming Zhu, Ivy Aneas, Noboru J Sakabe, Lunfeng Zhang, Debora R Sobreira, Lindsey E Montefiori, Julius Bogomolovas, Amelia C Joslin, Bin Zhou, Ju Chen, Marcelo Nobrega, Sylvia M Evans Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development published pages: CIRCRESAHA.118.3, ISSN: 0009-7330, DOI: 10.1161/CIRCRESAHA.118.311339 |
Circulation Research | 2019-09-02 |
| 2019 |
Xi Fang, Julius Bogomolovas, Christa Trexler, Ju Chen The BAG3-dependent and -independent roles of cardiac small heat shock proteins published pages: , ISSN: 2379-3708, DOI: 10.1172/jci.insight.126464 |
JCI Insight 4/4 | 2019-09-02 |
| 2019 |
Valeria Marrocco, Julius Bogomolovas, Elisabeth Ehler, Cristobal G. dos Remedios, Jiayu Yu, Chen Gao, Stephan Lange PKC and PKN in heart disease published pages: 212-226, ISSN: 0022-2828, DOI: 10.1016/j.yjmcc.2019.01.029 |
Journal of Molecular and Cellular Cardiology 128 | 2019-09-02 |
| 2017 |
Thomas Moore-Morris, Paola Cattaneo, Nuno Guimarães-Camboa, Julius Bogomolovas, Marta Cedenilla, Indroneal Banerjee, Mercedes Ricote, Tatiana Kisseleva, Lunfeng Zhang, Yusu Gu, Nancy D Dalton, Kirk L Peterson, Ju Chen, Michel Puceat, Sylvia M Evans Infarct Fibroblasts Do Not Derive From Bone Marrow Lineages published pages: CIRCRESAHA.117.3, ISSN: 0009-7330, DOI: 10.1161/circresaha.117.311490 |
Circulation Research | 2019-09-02 |
| 2017 |
Tongbin Wu, Yongxin Mu, Julius Bogomolovas, Xi Fang, Jennifer Veevers, Roberta B. Nowak, Christopher T. Pappas, Carol C. Gregorio, Sylvia M. Evans, Velia M. Fowler, Ju Chen HSPB7 is indispensable for heart development by modulating actin filament assembly published pages: 11956-11961, ISSN: 0027-8424, DOI: 10.1073/pnas.1713763114 |
Proceedings of the National Academy of Sciences 114/45 | 2019-09-02 |
| 2017 |
Xi Fang, Julius Bogomolovas, Tongbin Wu, Wei Zhang, Canzhao Liu, Jennifer Veevers, Matthew J. Stroud, Zhiyuan Zhang, Xiaolong Ma, Yongxin Mu, Dieu-Hung Lao, Nancy D. Dalton, Yusu Gu, Celine Wang, Michael Wang, Yan Liang, Stephan Lange, Kunfu Ouyang, Kirk L. Peterson, Sylvia M. Evans, Ju Chen Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy published pages: 3189-3200, ISSN: 0021-9738, DOI: 10.1172/JCI94310 |
Journal of Clinical Investigation 127/8 | 2019-09-02 |
| 2016 |
Julijus Bogomolovas, Egidijus Šimoliūnas, Ieva Rinkūnaitė, Luka Smalinskaitė, Andrej Podkopajev, Daiva Bironaitė, Cleo-Aron Weis, Alexander Marx, Virginija Bukelskienė, Norbert Gretz, Virginija Grabauskienė, Dittmar Labeit, Siegfried Labeit A Novel Murine Model of Parvovirus Associated Dilated Cardiomyopathy Induced by Immunization with VP1-Unique Region of Parvovirus B19 published pages: 1-9, ISSN: 2314-6133, DOI: 10.1155/2016/1627184 |
BioMed Research International 2016 | 2019-09-02 |
| 2016 |
Tiankun Zhou, Jennifer R. Fleming, Barbara Franke, Julius Bogomolovas, Igor Barsukov, Daniel J. Rigden, Siegfried Labeit, Olga Mayans CARP interacts with titin at a unique helical N2A sequence and at the domain Ig81 to form a structured complex published pages: 3098-3110, ISSN: 0014-5793, DOI: 10.1002/1873-3468.12362 |
FEBS Letters 590/18 | 2019-09-02 |
| 2016 |
Julius Bogomolovas, Alexander Gasch, Vilhelmas Bajoras, DovilÄ— KarÄiauskaitÄ—, Pranas Å erpytis, Virginija GrabauskienÄ—, Dittmar Labeit, Siegfried Labeit Cardiac specific titin N2B exon is a novel sensitive serological marker for cardiac injury published pages: 232-234, ISSN: 0167-5273, DOI: 10.1016/j.ijcard.2016.03.045 |
International Journal of Cardiology 212 | 2019-09-02 |
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