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  1. Article ; Online: Enhancing Cardiomyocyte Transcription Using In Vivo CRISPR/Cas9 Systems.

    Schoger, Eric / Zelarayán, Laura C

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2573, Page(s) 53–61

    Abstract: Endogenous gene activation by programmable transcription factors offers gene-dose-dependent phenotyping of target cells embedded in their in vivo natural tissue environment. Modified CRISPR/Cas9 systems were developed to be used as guide (g) RNA ... ...

    Abstract Endogenous gene activation by programmable transcription factors offers gene-dose-dependent phenotyping of target cells embedded in their in vivo natural tissue environment. Modified CRISPR/Cas9 systems were developed to be used as guide (g) RNA programmable transcriptional activation platforms (CRISPRa) in vitro and in vivo allowing targeted or multiplexed gene activation studies. We specifically developed these tools to be applied in cardiomyocytes providing dCas9VPR expressing mice under the control of the Myosin heavy chain 6 (Myh6) promoter. Here, we describe a protocol for the efficient design and validation of newly identified gRNA for enhancing transcriptional activity of a selected gene of interest. Additionally, we are providing insights into a downstream application in a dCas9VPR expressing mouse model specifically for cardiomyocyte biology.
    MeSH term(s) Animals ; CRISPR-Cas Systems/genetics ; Mice ; Myocytes, Cardiac ; RNA, Guide, CRISPR-Cas Systems/genetics ; Transcription Factors/genetics ; Transcriptional Activation
    Chemical Substances RNA, Guide, CRISPR-Cas Systems ; Transcription Factors
    Language English
    Publishing date 2022-08-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2707-5_5
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  2. Article: Preclinical evaluation of CRISPR-based therapies for Noonan syndrome caused by deep-intronic

    Knauer, Carolin / Haltern, Henrike / Schoger, Eric / Kügler, Sebastian / Roos, Lennart / Zelarayán, Laura C / Hasenfuss, Gerd / Zimmermann, Wolfram-Hubertus / Wollnik, Bernd / Cyganek, Lukas

    Molecular therapy. Nucleic acids

    2024  Volume 35, Issue 1, Page(s) 102123

    Abstract: Gene variants ... ...

    Abstract Gene variants in
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2024.102123
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  3. Book ; Online ; Thesis: In vivo application of CRISPR/Cas9 mediated gene re-expression in the failing mouse and human myocardium

    Schoger, Eric [Verfasser] / Zelarayán, Laura C. [Akademischer Betreuer] / Schwappach, Blanche [Gutachter] / Behr, Rüdiger [Gutachter] / Meyer, Thomas [Gutachter]

    2022  

    Author's details Eric Schoger ; Gutachter: Blanche Schwappach, Rüdiger Behr, Thomas Meyer ; Betreuer: Laura C. Zelarayán
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language German
    Publisher Niedersächsische Staats- und Universitätsbibliothek Göttingen
    Publishing place Göttingen
    Document type Book ; Online ; Thesis
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  4. Article ; Online: Inhibition of Prolyl-Hydroxylase Domain Enzymes Protects From Reoxygenation Injury in Engineered Human Myocardium.

    Levent, Elif / Noack, Claudia / Zelarayán, Laura C / Katschinski, Dörthe M / Zimmermann, Wolfram-Hubertus / Tiburcy, Malte

    Circulation

    2020  Volume 142, Issue 17, Page(s) 1694–1696

    MeSH term(s) Humans ; Myocardium/enzymology ; Prolyl Hydroxylases/metabolism
    Chemical Substances Prolyl Hydroxylases (EC 1.14.11.-)
    Language English
    Publishing date 2020-10-26
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.119.044471
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    Ui IV Zs.60: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Book ; Online ; Thesis: Wnt-TCF7L2-dependent transcriptional and chromatin dynamics in cardiac regeneration, homeostasis and disease

    Iyer, Lavanya Muthukrishnan [Verfasser] / Zelarayán, Laura C. [Akademischer Betreuer] / Zelarayán, Laura C. [Gutachter] / Johnsen, Steven A. [Gutachter]

    2018  

    Author's details Lavanya Muthukrishnan Iyer ; Gutachter: Laura C. Zelarayán, Steven A. Johnsen ; Betreuer: Laura C. Zelarayán
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Niedersächsische Staats- und Universitätsbibliothek Göttingen
    Publishing place Göttingen
    Document type Book ; Online ; Thesis
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  6. Article ; Online: Single-cell transcriptomics reveal extracellular vesicles secretion with a cardiomyocyte proteostasis signature during pathological remodeling.

    Schoger, Eric / Bleckwedel, Federico / Germena, Giulia / Rocha, Cheila / Tucholla, Petra / Sobitov, Izzatullo / Möbius, Wiebke / Sitte, Maren / Lenz, Christof / Samak, Mostafa / Hinkel, Rabea / Varga, Zoltán V / Giricz, Zoltán / Salinas, Gabriela / Gross, Julia C / Zelarayán, Laura C

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 79

    Abstract: Aberrant Wnt activation has been reported in failing cardiomyocytes. Here we present single cell transcriptome profiling of hearts with inducible cardiomyocyte-specific Wnt activation (β- ... ...

    Abstract Aberrant Wnt activation has been reported in failing cardiomyocytes. Here we present single cell transcriptome profiling of hearts with inducible cardiomyocyte-specific Wnt activation (β-cat
    MeSH term(s) Mice ; Humans ; Animals ; Myocytes, Cardiac/metabolism ; Proteostasis ; Proteomics ; Transcriptome ; Induced Pluripotent Stem Cells/metabolism ; Proteins/metabolism ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Gene Expression Profiling
    Chemical Substances Proteins
    Language English
    Publishing date 2023-01-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-022-04402-9
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  7. Article ; Online: Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced Cardiac Dysfunction.

    Sayour, Nabil V / Tóth, Viktória É / Nagy, Regina N / Vörös, Imre / Gergely, Tamás G / Onódi, Zsófia / Nagy, Noémi / Bödör, Csaba / Váradi, Barnabás / Ruppert, Mihály / Radovits, Tamás / Bleckwedel, Federico / Zelarayán, Laura C / Pacher, Pal / Ágg, Bence / Görbe, Anikó / Ferdinandy, Péter / Varga, Zoltán V

    International journal of molecular sciences

    2023  Volume 24, Issue 18

    Abstract: The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. ... ...

    Abstract The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs via droplet digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of left ventricular pressure-overload; (ii) to compare RNAseq findings with those of ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF. Male Wistar rats subjected to transverse aortic constriction (TAC,
    MeSH term(s) Male ; Rats ; Mice ; Animals ; Rats, Wistar ; Heart Failure/genetics ; Myocytes, Cardiac ; Polymerase Chain Reaction ; Hypertrophy
    Language English
    Publishing date 2023-09-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241813826
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  8. Book ; Online ; Thesis: TET3 IMPACTS CARDIAC FIBROSIS PARTIALLY VIA REGULATION OF DNA DAMAGE RESPONSE

    Rath, Sandip Kumar [Verfasser] / Zeisberg, Elisabeth [Akademischer Betreuer] / Katschinski, Dörthe [Gutachter] / Zelarayán, Laura C. [Gutachter]

    2020  

    Author's details Sandip Kumar Rath ; Gutachter: Dörthe Katschinski, Laura C. Zelarayán ; Betreuer: Elisabeth Zeisberg
    Keywords Medizin, Gesundheit ; Medicine, Health
    Subject code sg610
    Language English
    Publisher Niedersächsische Staats- und Universitätsbibliothek Göttingen
    Publishing place Göttingen
    Document type Book ; Online ; Thesis
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  9. Article ; Online: Moving toward gender equity in the cardiology and cardiovascular research workforce in Germany: a report from the German Cardiac Society.

    Lerchenmüller, Carolin / Zelarayan, Laura / Streckfuss-Bömeke, Katrin / Gimenez, Maria Rubini / Schnabel, Renate / Hashemi, Djawid / Baldus, Stephan / Rudolph, Tanja K / Morbach, Caroline

    European heart journal open

    2023  Volume 3, Issue 2, Page(s) oead034

    Abstract: Aims: Although the share of women in cardiology in Germany is growing steadily, this does not translate into leadership positions. Medical societies play a crucial role in shaping the national and international medical and scientific environment. The ... ...

    Abstract Aims: Although the share of women in cardiology in Germany is growing steadily, this does not translate into leadership positions. Medical societies play a crucial role in shaping the national and international medical and scientific environment. The German Cardiac Society (DGK) aims to serve the public discourse on gender-equity by systematic analysis of data on gender representation within the society and in Germany.
    Methods and results: We present gender disaggregated data collection of members, official organs, working groups, scientific meetings, as well as awards of the DGK based on anonymized exports from the DGK office as well as on data gathered from the DGK web page. From 2000 to 2020, the overall number of DGK members as well as the share of women increased (12.5% to 25.3%). In 2021, the share of women ranged from 40% to 50% in earlier career stages but was substantially lower at senior levels (23.9% of consulting/attending physicians, 7.1% of physicians-in-chief, 3.4% of directors). The share of women serving in DGK working groups had gained overall proportionality, but nuclei and speaker positions were largely held by men. Boards and project groups were predominantly represented by men as well. At the DGK-led scientific meetings, women contributed more often in junior relative to (invited) senior roles.
    Conclusion: Increasing numbers of women in cardiology and in the DGK over the past 20 years did not translate into the respective increase in representation of women in leadership positions. There is an urgent need to identify and, more importantly, to overcome barriers towards gender equity. Transparent presentation of society-related data is the first step for future targeted actions in this regard.
    Language English
    Publishing date 2023-03-29
    Publishing country England
    Document type Journal Article
    ISSN 2752-4191
    ISSN (online) 2752-4191
    DOI 10.1093/ehjopen/oead034
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  10. Article ; Online: Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice.

    Chen, Yanpu / Lüttmann, Felipe F / Schoger, Eric / Schöler, Hans R / Zelarayán, Laura C / Kim, Kee-Pyo / Haigh, Jody J / Kim, Johnny / Braun, Thomas

    Science (New York, N.Y.)

    2021  Volume 373, Issue 6562, Page(s) 1537–1540

    Abstract: ... that heart-specific expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) induces adult CMs to dedifferentiate ...

    Abstract Cardiomyocyte (CM) replacement is very slow in adult mammalian hearts, preventing regeneration of damaged myocardium. By contrast, fetal hearts display considerable regenerative potential owing to the presence of less mature CMs that still have the ability to proliferate. In this study, we demonstrate that heart-specific expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) induces adult CMs to dedifferentiate, conferring regenerative capacity to adult hearts. Transient, CM-specific expression of OSKM extends the regenerative window for postnatal mouse hearts and induces a gene expression program in adult CMs that resembles that of fetal CMs. Extended expression of OSKM in CMs leads to cellular reprogramming and heart tumor formation. Short-term OSKM expression before and during myocardial infarction ameliorates myocardial damage and improves cardiac function, demonstrating that temporally controlled dedifferentiation and reprogramming enable cell cycle reentry of mammalian CMs and facilitate heart regeneration.
    MeSH term(s) Actins/genetics ; Actins/metabolism ; Animals ; Cell Dedifferentiation ; Cell Proliferation ; Cellular Reprogramming ; Doxycycline/pharmacology ; Gene Expression ; Heart/embryology ; Heart/physiology ; Heart Neoplasms/pathology ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism ; Mice ; Mitosis ; Myocardial Infarction/pathology ; Myocardial Infarction/physiopathology ; Myocardial Infarction/therapy ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/physiology ; Octamer Transcription Factor-3/genetics ; Octamer Transcription Factor-3/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Regeneration ; SOXB1 Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism
    Chemical Substances Actins ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors ; Myc protein, mouse ; Octamer Transcription Factor-3 ; Pou5f1 protein, mouse ; Proto-Oncogene Proteins c-myc ; SOXB1 Transcription Factors ; Sox2 protein, mouse ; Doxycycline (N12000U13O)
    Language English
    Publishing date 2021-09-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abg5159
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 27: Show issues Location:
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