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Titin Signals SIGNED

Molecular dissection of titin-based mechanisms in charge of cardiomyocyte dysfunction in terminal feart failure

Total Cost €

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EC-Contrib. €

0

Partnership

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 Titin Signals project word cloud

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

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Project "Titin Signals" data sheet

The following table provides information about the project.

Coordinator
ZENTRALINSTITUT FUER SEELISCHE GESUNDHEIT 

Organization address
address: Square J 5
city: MANNHEIM
postcode: 68159
website: www.zi-mannheim.de

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 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.

# participants  country  role  EC contrib. [€] 
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

List of 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
List of publications.
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, Dovilė Karčiauskaitė, Pranas Šerpytis, Virginija Grabauskienė, 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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