Iyer, Lavanya M.

[["dc.bibliographiccitation.artnumber","P4479"],["dc.bibliographiccitation.firstpage","937"],["dc.bibliographiccitation.issue","suppl_1"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Iyer, L. M."],["dc.contributor.author","Noack, C."],["dc.contributor.author","Nagarajan, S."],["dc.contributor.author","Woelfer, M."],["dc.contributor.author","Schoger, E."],["dc.contributor.author","Pang, S. T."],["dc.contributor.author","Kari, V."],["dc.contributor.author","Zafeiriou, M. P."],["dc.contributor.author","Toischer, K."],["dc.contributor.author","Hasenfuss, G."],["dc.contributor.author","Johnsen, S. A."],["dc.contributor.author","Zelarayan, L. C."],["dc.date.accessioned","2019-02-19T13:47:43Z"],["dc.date.available","2019-02-19T13:47:43Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1093/eurheartj/ehx504.P4479"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57586"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/177"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation.issn","0195-668X"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.title","B-catenin/TCF7L2 signaling orchestrates initiation of pathological hypertrophic cardiac remodeling by inducing chromatin modifications"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.contributor.author","Rathjens, Franziska S."],["dc.contributor.author","Blenkle, Alica"],["dc.contributor.author","Iyer, Lavanya M."],["dc.contributor.author","Renger, Anke"],["dc.contributor.author","Syeda, Fahima"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Jungmann, Andreas"],["dc.contributor.author","Dewenter, Matthias"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Zafeiriou, Maria Patapia"],["dc.date.accessioned","2021-06-01T10:51:17Z"],["dc.date.available","2021-06-01T10:51:17Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Aims  Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mechanisms, we aimed to reveal the ventricular TBX5-dependent transcriptional network and further test the therapeutic potential of TBX5 level normalization in mice with documented arrhythmias. Methods and results  We used a mouse model of TBX5 conditional deletion in ventricular cardiomyocytes. Ventricular (v) TBX5 loss in mice resulted in mild cardiac dysfunction and arrhythmias and was associated with a high mortality rate (60%) due to SCD. Upon angiotensin stimulation, vTbx5KO mice showed exacerbated cardiac remodelling and dysfunction suggesting a cardioprotective role of TBX5. RNA-sequencing of a ventricular-specific TBX5KO mouse and TBX5 chromatin immunoprecipitation was used to dissect TBX5 transcriptional network in cardiac ventricular tissue. Overall, we identified 47 transcripts expressed under the control of TBX5, which may have contributed to the fatal arrhythmias in vTbx5KO mice. These included transcripts encoding for proteins implicated in cardiac conduction and contraction (Gja1, Kcnj5, Kcng2, Cacna1g, Chrm2), in cytoskeleton organization (Fstl4, Pdlim4, Emilin2, Cmya5), and cardiac protection upon stress (Fhl2, Gpr22, Fgf16). Interestingly, after TBX5 loss and arrhythmia development in vTbx5KO mice, TBX5 protein-level normalization by systemic adeno-associated-virus (AAV) 9 application, re-established TBX5-dependent transcriptome. Consequently, cardiac dysfunction was ameliorated and the propensity of arrhythmia occurrence was reduced. Conclusions  This study uncovers a novel cardioprotective role of TBX5 in the adult heart and provides preclinical evidence for the therapeutic value of TBX5 protein normalization in the control of arrhythmia."],["dc.identifier.doi","10.1093/cvr/cvaa239"],["dc.identifier.pmid","32777030"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86956"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/211"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/380"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.relation.workinggroup","RG Zafeiriou (3D Electrically Excitable Cell Networks – Brain and Heart)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY-NC 4.0"],["dc.title","Preclinical evidence for the therapeutic value of TBX5 normalization in arrhythmia control"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1119"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Europace"],["dc.bibliographiccitation.lastpage","1131"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Hofhuis, Julia"],["dc.contributor.author","Bersch, Kristina"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Molina, Cristina Espinosa"],["dc.contributor.author","Fakuade, Funsho E."],["dc.contributor.author","Iyer, Lavanya M."],["dc.contributor.author","Streckfuß-Bömeke, Katrin"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Zelarayan, Laura Cecilia"],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Maier, Lars Siegfried"],["dc.contributor.author","Klinge, Lars"],["dc.contributor.author","Thoms, Sven"],["dc.date.accessioned","2020-08-10T05:34:04Z"],["dc.date.available","2020-08-10T05:34:04Z"],["dc.date.issued","2020"],["dc.description.abstract","The multi-C2 domain protein dysferlin localizes to the T-Tubule system of skeletal and heart muscles. In skeletal muscle, dysferlin is known to play a role in membrane repair and in T-tubule biogenesis and maintenance. Dysferlin deficiency manifests as muscular dystrophy of proximal and distal muscles. Cardiomyopathies have been also reported, and some dysferlinopathy mouse models develop cardiac dysfunction under stress. Generally, the role and functional relevance of dysferlin in the heart is not clear. The aim of this study was to analyse the effect of dysferlin deficiency on the transverse-axial tubule system (TATS) structure and on Ca2+ homeostasis in the heart."],["dc.identifier.doi","10.1093/europace/euaa093"],["dc.identifier.pmid","32572487"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/67547"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/360"],["dc.language.iso","en"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A10: Peroxisomen als modulatorische Einheiten im Herzstoffwechsel und bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation","SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1002 | A13: Bedeutung einer gestörten zytosolischen Calciumpufferung bei der atrialen Arrhythmogenese bei Patienten mit Herzinsuffizienz (HF)"],["dc.relation.eissn","1532-2092"],["dc.relation.issn","1099-5129"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Thoms (Biochemistry and Molecular Medicine)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.title","Dysferlin links excitation-contraction coupling to structure and maintenance of the cardiac transverse-axial tubule system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2850"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","2867"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Iyer, Lavanya M"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Woelfer, Monique"],["dc.contributor.author","Schoger, Eric"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Zafiriou, Maria Patapia"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Pang, Sze Ting"],["dc.contributor.author","Weber, Tobias"],["dc.contributor.author","Rathjens, Franziska S."],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Zelarayán, Laura C."],["dc.date.accessioned","2018-04-23T11:47:57Z"],["dc.date.available","2018-04-23T11:47:57Z"],["dc.date.issued","2018"],["dc.description.abstract","Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression. This enhances active chromatin, characterized by increased H3K27ac and TCF7L2 occupancies to cardiac developmental and remodelling genes in vivo. Accordingly, transcriptomic analysis of β-catenin stabilized hearts shows a strong recapitulation of cardiac developmental processes like cell cycling and cytoskeletal remodelling. Mechanistically, TCF7L2 co-occupies distal genomic regions with cardiac transcription factors NKX2–5 and GATA4 in stabilized-β-catenin hearts. Validation assays revealed a previously unrecognized function of GATA4 as a cardiac repressor of the TCF7L2/β-catenin complex in vivo, thereby defining a transcriptional switch controlling disease progression. Conversely, preventing β-catenin activation post-pressure-overload results in a downregulation of these novel TCF7L2-targets and rescues cardiac function. Thus, we present a novel role for TCF7L2/β-catenin in CMs-specific chromatin modulation, which could be exploited for manipulating the ubiquitous Wnt pathway."],["dc.description.sponsorship","Open-Access-Publikatinsfonds 2018"],["dc.identifier.doi","10.1093/nar/gky049"],["dc.identifier.gro","3142314"],["dc.identifier.pmid","29394407"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15089"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13447"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/201"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A11: Absolute Arrhythmie bei Vorhofflimmern - ein neuer Mechanismus, der zu einer Störung von Ca2+-Homöostase und elektrischer Stabilität in der Transition zur Herzinsuffizienz führt"],["dc.relation","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation","SFB 1002 | INF: Unterstützung der SFB 1002 Forschungsdatenintegration, -visualisierung und -nachnutzung"],["dc.relation.issn","0305-1048"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","A context-specific cardiac β-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]