UKE Homepage
DE
Research Group Stenzig
Cardiac epigenetics in heart failure, fibrosis and arrhythmia
Aim:
We aim to understand how DNA methylation contributes to heart disease and may represent a therapeutic target.
Scope of Research
DNA Methylation • Cardiac Tissue Engineering • Optogenetics and Arrhythmia • Pharmacology
Research Projects
1. How cardiac fibroblasts react to cardiomyocyte signaling – focus on epigenetic signal integration.
This DFG-funded project aims to identify signatures of epigenetic transformation during cardiac fibroblast pro-fibrotic activation. Importantly, we are investigating mechanisms by which cardiomyocytes signal towards fibroblasts, which then leads to epigenetic changes, with the goal to identify cardiac-specific, epigenetics-based anti-fibrotic therapeutic targets. Sandra Gajewsky in our group engineered a novel DNA-methyl transferase 3A-knock out cell line, which we now employ for this project.
2. Investigation of pro-inflammatory mechanisms in atrial engineered heart tissue.
In this collaboration project with the group of Prof. Marc Hirt, we use optogenetically paced human induced pluripotent stem cell-derived atrial engineered heart tissue (hiPSC-aEHT) and amend it with the inclusion of hiPSC-derived macrophages and fibroblasts. We aim to identify mechanisms by which fast and/or arrhythmic beating leads to pro-inflammatory processes in atrial fibrillation and, vice versa, how these may add to pro-arrhythmic propensity of the tissue. Jessica Schrapers from our group developed an advanced arrhythmic pacing model in our group, which we now employ for this project.
3. Acyl-carnitines in atrial fibrillation.
This project is the continuation of a long-standing collaboration within the DZHK with Prof. Tanja Zeller from the Institute of Cardiogenetics in Lübeck, Germany, in which we unravel mechanisms, by which circulating long-chain acyl-carnitines contribute to the pathophysiology of atrial fibrillation. For this project, Karl-Felix Müller in our group developed a model in which a fibrillation-like state can be induced in pre-conditioned aEHT and varies depending on their pro-arrhythmic propensity.
Key Techniques
- Human induced-pluripotent stem cell-derived engineered heart tissue
- Atrial stem cell-derived cardiomyocytes, stem-cell derived fibroblasts
- Optogenetic manipulation of engineered heart tissue
Group Members
Publications
-
An arrhythmogenic metabolite in atrial fibrillation.
Krause J, Nickel A, Madsen A, Aitken-Buck HM, Stoter AMS, Schrapers J, Ojeda F, Geiger K, Kern M, Kohlhaas M, Bertero E, Hofmockel P, Hübner F, Assum I, Heinig M, Müller C, Hansen A, Krause T, Park DD, Just S, Aïssi D, Börnigen D, Lindner D, Friedrich N, Alhussini K, Bening C, Schnabel RB, Karakas M, Iacoviello L, Salomaa V, Linneberg A, Tunstall-Pedoe H, Kuulasmaa K, Kirchhof P, Blankenberg S, Christ T, Eschenhagen T, Lamberts RR, Maack C, Stenzig J*, Zeller T* (2023).
J Transl Med. 24;21(1):566. *Equal contribution.
-
Recapitulation of dyssynchrony-associated contractile impairment in asymmetrically paced engineered heart tissue.
Stenzig J, Lemoine MD, Stoter AMS, Wrona KM, Lemme M, Mulla W, Etzion Y, Eschenhagen T, Hirt MN (2022).
J Mol Cell Cardiol, 163:97-105.
-
An Important Role for DNMT3A-Mediated DNA Methylation in Cardiomyocyte Metabolism and Contractility.
Madsen A, Höppner G, Krause J, Hirt MN, Laufer SD, Schweizer M, Tan WLW, Mosqueira D, Anene-Nzelu CG, Lim I, Foo RSY, Eschenhagen T, Stenzig J (2020).
Circulation, 142:1562–1578.
-
Rat atrial engineered heart tissue: a new in vitro model to study atrial biology.
Krause J, Löser A, Lemoine MD, Christ T, Scherschel K, Meyer C, Blankenberg S, Zeller T, Eschenhagen T, Stenzig J (2018).
Basic Res Cardiol 113(5):41.
-
DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors.
Stenzig J, Hirt MN, Löser A, Bartholdt LM, Hensel JT, Werner TR, Riemenschneider M, Indenbirken D, Guenther T, Müller C, Hübner N, Stoll M, Eschenhagen T (2016).
Basic Res Cardiol. 111(1):9.
Grants/Awards
- DFG-Sachbeihilfe: Reaktionen von Fibroblasten auf Signale von Kardiomyozyten - Untersuchung mit Fokus auf epigenetische Signalintegration
Most important collaboration partners
- Prof. Dr. Tanja Zeller, Institute for Cardiogenetics, University of Lübeck, Germany
- Prof. Dr. Roger Foo, Cardiovascular Research Institute, National University of Singapore, Singapore
- Prof. Dr. Larissa Fabritz, Department of Cardiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Dr. Thomas Moore-Morris, Institute of Functional Genomics, University of Montpellier, Montpellier, France
- Prof. Dr. Chukwuemeka George Anene-Nzelu, Montreal Heart Institute, Montreal, Canada