Iyer, Lavanya M.

[["dc.bibliographiccitation.firstpage","51"],["dc.bibliographiccitation.journal","Progress in Biophysics and Molecular Biology"],["dc.bibliographiccitation.lastpage","60"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Schlick, Susanne F."],["dc.contributor.author","Spreckelsen, Florian"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Iyer, Lavanya M."],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Zelarayan, Laura C."],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Parlitz, Ulrich"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Rehfeldt, Florian"],["dc.date.accessioned","2020-12-10T15:20:42Z"],["dc.date.available","2020-12-10T15:20:42Z"],["dc.date.issued","2019"],["dc.description.abstract","Cardiomyocyte and stroma cell cross-talk is essential for the formation of collagen-based engineered heart muscle, including engineered human myocardium (EHM). Fibroblasts are a main component of the myocardial stroma. We hypothesize that fibroblasts, by compacting the surrounding collagen network, support the self-organization of cardiomyocytes into a functional syncytium. With a focus on early self-organization processes in EHM, we studied the molecular and biophysical adaptations mediated by defined populations of fibroblasts and embryonic stem cell-derived cardiomyocytes in a collagen type I hydrogel. After a short phase of cell-independent collagen gelation (30 min), tissue compaction was progressively mediated by fibroblasts. Fibroblast-mediated tissue stiffening was attenuated in the presence of cardiomyocytes allowing for the assembly of stably contracting, force-generating EHM within 4 weeks. Comparative RNA-sequencing data corroborated that fibroblasts are particularly sensitive to the tissue compaction process, resulting in the fast activation of transcription profiles, supporting heart muscle development and extracellular matrix synthesis. Large amplitude oscillatory shear (LAOS) measurements revealed nonlinear strain stiffening at physiological strain amplitudes (>2%), which was reduced in the presence of cells. The nonlinear stress-strain response could be characterized by a mathematical model. Collectively, our study defines the interplay between fibroblasts and cardiomyocytes during human heart muscle self-organization in vitro and underscores the relevance of fibroblasts in the biological engineering of a cardiomyogenesis-supporting viscoelastic stroma. We anticipate that the established mathematical model will facilitate future attempts to optimize EHM for in vitro (disease modelling) and in vivo applications (heart repair)."],["dc.identifier.doi","10.1016/j.pbiomolbio.2018.11.011"],["dc.identifier.pmid","30553553"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72769"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/248"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["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 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.workinggroup","RG Luther (Biomedical Physics)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY 4.0"],["dc.title","Agonistic and antagonistic roles of fibroblasts and cardiomyocytes on viscoelastic stiffening of engineered human myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["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","1804"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","1819"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Iyer, Lavanya M."],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Schoger, Eric"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Wagner, Eva"],["dc.contributor.author","Woelfer, Monique"],["dc.contributor.author","Zafiriou, Maria-Patapia"],["dc.contributor.author","Milting, Hendrik"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Zelarayán, Laura C."],["dc.date.accessioned","2020-12-10T14:24:44Z"],["dc.date.available","2020-12-10T14:24:44Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.jacc.2019.07.076"],["dc.identifier.pmid","31582141"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16513"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72339"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/283"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["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 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","KLF15-Wnt–Dependent Cardiac Reprogramming Up-Regulates SHISA3 in the Mammalian Heart"],["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","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"]]