AG Hansen


Name: Prof. Dr. med. Arne Hansen
Clinic/Institute: Institute of Experimental Pharmacology and Toxicology
Email: ar.hansen@uke.de
Phone: +49 (0) 40 7410 - 57207

Research Focus and Main research questions

Arne Hansen’s research team aims to develop complex cardiac in vitro models and applies them to study disease mechanisms of the heart. His work is driven by the hypothesis that human in vitro models are complementary, predictive and provide useful insight.

To reach these goals his group employs human induced pluripotent stem cell reprogramming and expansion, CRISPR/Cas9 genome editing, cardiomyocyte subtype differentiation and tissue engineering protocols as versatile tools for biomedical model development. His group develops and employs customized test systems with automated readout of physiological parameters like action potential, calcium transient and contractile force, enabling to investigate cardiac gene and drug effects with high levels of standardization. By combining automated functional analysis with surrogates for cardiac cell biology (e.g. metabolism, apoptosis, proliferation) his research group aims to deepen the understanding of cardiac biology and cardiomyopathy mechanisms. The long-term perspective of this research focus is to contribute to the development of well characterized human in vitro models closely replicating physiology and disease mechanisms and thereby to facilitate biomedical translation.

  • Methods
  • Methods

    Methods:

    • Human induced pluripotent stem cells
    • CRISPR/Cas9 genome engineering
    • Engineered heart tissue

  • Publications:

    Cuello F, Knaust AE, Saleem U, Loos M, Janice Raabe J, Mosqueira D, Laufer S, Schweizer M, Kraak Pvd, Flenner F, Ulmer BM, Braren I, Yin X, Theofilatos K, Ruiz-Orera J, Patone G, Klampe B, Schulze T, Piasecki A, Pinto Y, Vink A, Hübner N, Harding S, Mayr M, Denning C, Eschenhagen T, Hansen A (2021). Impairment of the ER/mitochondria compartment in human cardiomyocytes with PLN p.Arg14del mutation, accepted EMBO MolMed.

    Saleem U, Braren I, Mannhardt I, Denning C, Eschenhagen T, Hansen A (2020). Force and calcium transient analysis in human engineered heart tissues reveals positive force-frequency relation at physiological frequency. Stem Cell Reports,14(2):312–324. PMID 31956082

    Saleem U, Ismaili D, Mannhardt I, Pinnschmidt H, Schulze T, Christ T, Eschenhagen T, Hansen A (2020). Regulation of I Ca,L and force by PDEs in human-induced pluripotent stem cell-derived cardiomyocytes. Br J Pharmacol;177(13):3036-3045.

    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. Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium. Stem Cell Reports. 2018 Dec 11;11(6):1378-1390. PMID 30416051

    Mosqueira D, Mannhardt I, Bhagwan JR, Lis-Slimak K, Katili P, Scott E, Hassan M, Prondzynski M, Harmer SC, Tinker A, Smith JGW, Carrier L, Williams PM, Gaffney D, Eschenhagen T, Hansen A, Denning C. CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy. Eur. Heart J. (2018). PMID 29741611

    Ulmer BM, Stoehr A, Mannhardt I, Patel S, Gucek M, Schulze ML, Murphy E, Eschenhagen T, Hansen A. Contractile work contributes to maturation of energy metabolism in hiPSC-derived cardiomyocytes. Stem cell reports 10, 834–847 (2018). PMID 29503093

    Mannhardt I, Eder A, Dumotier B, Prondzynski M, Krämer E, Traebert M, Söhren KD, Flenner F, Stathopoulou K, Lemoine M, Carrier L, Christ T, Eschenhagen T, Hansen A. Blinded contractility analysis in hiPSC-cardiomyocytes in engineered heart tissue format: Comparison with human atrial trabeculae. Toxicol Sci. 2017 Apr 27. doi: 10.1093/toxsci/kfx081. PMID 28453742

    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, Marita L. Rodriguez ML, Eschenhagen T, Hansen A. Differentiation of cardiomyocytes and generation of human Engineered Heart Tissue. Nat Protoc. 2017 Jun;12(6):1177-1197. PMID 28492526

    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. Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells. Sci Transl Med. 2016 Nov 2;8(363):363ra148. PMID 27807283

    Mannhardt I, Breckwoldt K, Letuffe-Brenière D, Schaaf S, Schulz H, Neuber C, Benzin A, Werner T, Eder A, Schulze T, Klampe B, Christ T, Hirt MN, Huebner N, Moretti A, Eschenhagen T, Hansen A. Human Engineered Heart Tissue: Analysis of Contractile Force. Stem Cell Reports. 2016 Jul 12;7(1):29-42. PMID 27211213

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