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Research Group Eschenhagen
Heart failure mechanisms and innovative therapeutic approaches
Aim
We aim to understand cardiac excitation-contraction coupling and, together with AG Christ, the role of PITX2 in the pathogenesis of atrial fibrillation with hiPSC-derived cardiomyocytes and engineered heart tissue.
Scope of Research
Heart Failure • Cardiac Myocyte Biology • Excitation-Contraction-Coupling • Cardiac Regeneration
Research Projects
1. Contribution of SERCA2, RyR2, NCX1 and PMCA to excitation-contraction coupling in human cardiomyocytes – tackling an old question with modern technologies. We study the impact of the respective gene knockouts (alone and in combination) on the contractile function and intracellular calcium cycling in hiPSC-derived cardiomyocytes and engineered heart tissue.
2. Impact of genes in the PITX2 locus on the electrophysiology of human atrial induced pluripotent stem cell-derived cardiomyocytes. We evaluate whether the atrial fibrillation-like phenotype in PITX2 knockout atrial EHTs is reversed by overexpressing PITX2 or reversing accompanying alterations of the transcriptome.
3. Improving cardiac repair with hiPSC-derived cardiomyocytes by transient stimulation of proliferation. We aim at substantially increasing current graft size by transiently stimulating proliferation of hiPSC-cardiomyocytes after transplantation, using regulatable or transient expression of a constitutively active version of ERBB2.
Key Techniques
- Knockout/knockin of genes and indicators by CRISPR/Cas9 technology in human induced pluripotent stem cell-derived cardiomyocytes
- AAV-mediated expression of genetically encoded calcium indicators
- Evaluation of the function in cardiomyocytes, engineered heart tissue and mice (echocardiography)
- Live cell imaging and confocal microscopy
- Molecular biology
Group Members
Michelle Hattel,
MD student;
Margaret Nandudu,
PhD student;
Lukas Narjes,
MD Student;
Marie Nehring,
PhD student;
Simona Parretta,
PhD student;
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Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells
Weinberger F, Breckwoldt K, Pecha S, Kelly A, Geertz B, Starbatty J, Yorgan T, Cheng KH, Lessmann K, Stolen T, Scherrer-Crosbie M, Smith G, Reichenspurner H, Hansen A, Eschenhagen T
Sci Transl Med 2016, 8: 363ra148. -
Differentiation of cardiomyocytes and generation of human engineered heart tissue
Breckwoldt K, Letuffe-Brenière D, Mannhardt I, Schulze T, Ulmer B, Werner T, Benzin A, Klampe B, Reinsch MC, Laufer S, Shibamiya A, Prondzynski M, Mearini G, Schade D, Fuchs S, Neuber C, Krämer E, Saleem U, Schulze ML, Rodriguez ML, Eschenhagen T, Hansen A
Nat Protoc 2017, 12:1177-1197 -
Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium
Lemme M, Ulmer BM, Lemoine MD, Zech ATL, Flenner F, Ravens U, Reichenspurner H, Rol-Garcia M, Smith G, Hansen A, Christ T, Eschenhagen T
Stem Cell Reports 2018, 11:1378-1390 -
Human Engineered Heart Tissue Patches Remuscularize the Injured Heart in a Dose-Dependent Manner
Querdel E, Reinsch M, Castro L, Köse D, Bähr A, Reich S, Geertz B, Ulmer B, Schulze M, Lemoine MD, Krause T, Lemme M, Sani J, Shibamiya A, Stüdemann T, Köhne M, von Bibra CV, Hornaschewitz N, Pecha S, Nejahsie Y, Mannhardt I, Christ T, Reichenspurner H, Hansen A, Klymiuk N, Krane M, Kupatt C, Eschenhagen T, Weinberger F
Circulation 2021, 143:1991-2006 -
Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury
Stüdemann T, Rössinger J, Manthey C, Geertz B, Srikantharajah R, von Bibra C, Shibamiya A, Köhne M, Wiehler A, Wiegert JS, Eschenhagen T, Weinberger F
Circulation 146:1159-1169
Grants/Awards
- 2022-2025
DFG (ES-88/16-1) – Influence of genes in the PITX2 locus on the electrophysiology of human atrial stem cell-derived cardiomyocytes – to Thomas Eschenhagen (Co-PIs Torsten Christ and Monika Stoll, Münster) - 2024-2027
DFG (ES/88-17-1) - Contribution of SERCA2, RyR2, NCX1 and PMCA to excitation-contraction coupling in human cardiomyocytes – tackling an old question with modern technologies – to Thomas Eschenhagen (Co-PI Torsten Christ) - 2025 – 2027
Deutsche Herzstiftung - Assoziation zwischen Einnahme von Pseudoephedrin-haltigen Erkältungsmitteln und Herzinfarkten – to Thomas Eschenhagen (Co-PI Edzard Schwedhelm, Johannes Neumann) - 2026-2030
German Center for Cardiovascular Research (DZHK) – High-throughput functional analysis of genetic DCM and aortopathy variants in pluripotent stem cell-derived cardiovascular cells – to Thomas Eschenhagen, co-Principal Investigator with Arne Hansen and Friederike Cuello (IEPT, UKE)
Prizes/Honors (Selection):
- 2025 Peter Harris Distinguished Scientist Award of the ISHR
- 2019 Brutsaert Award Lecture, ESC Heart Failure Association
- 2017 Member of the Academia Europeae
- 2016 President´s Award Lecture of the ISHR
- 2014 ERC Advanced Grant
- 2012 Outstanding Investigator Award of the ISHR
- 2011 Ursula M. Händel Animal Replacement Award (DFG)
- 2008 Member of the National Academy of Science Leopoldina
- 2004 Member of the Academy of Sciences, Göttingen
- 1997 Fraenkel Award, German Society of Cardiology (DGK)
- 1995 Sandoz Award, German Society for Pharmacology and Toxicology (DGPT)
Patents
- Matrixkörper für die Messung isometrischer Kraftparameter von Zellgewebe, Verfahren zum Herstellen des Matrixkörpers, Set für dieses Verfahren und Verwendung des Matrixkörpers zum Kultivieren von Kardiomyozyten (DPA 1995)
- Engineered muscle tissue for the in vitro analysis of effects of substances on the contractility of muscle, especially heart muscle cells (3D); EPA, USPO 2001/2002
- Use of CARB inhibitors for the treatment of heart diseases (EPA 2001)
- Pouch-like construct comprising mammalian tissue (EPA 2006)
- Gene-therapy vectors for treating cardiomyopathy (EPA14719704, US20160108430, CA2944186), 2014, licensed to DiNAQOR AG (2021)
Most important national and international collaboration partners:
- Monika Stoll, University of Münster and Maastricht
- Oliver Müller, University of Kiel
- Christoph Maack, University of Würzburg
- Manuel Mayr, Imperial College London, UK
- Yigal Pinto, University Medical Center Amsterdam, NL
- Christine Mummery, University of Leiden, NL