AG Cuello


Name: Prof. Dr. rer. nat. Friederike Cuello
Clinic/Institute: Institute of Experimental Pharmacology and Toxicology
Email: f.cuello@uke.de
Phone: +49 (0) 40 7410 - 57204

Research Focus and Main research questions

The scientific focus of the group is on studying the molecular pathomechanisms underlying cardiac and vascular disease development. In particular, we are interested in the dysregulation of signal transduction processes that occur due to alterations in protein kinase activation, activity, localization and post-translational modification. Studies are performed in knock-in mouse models, isolated primary cardiomyocytes or in three-dimensional engineered tissue from human induced-pluripotent stem cell (hiPSC)-derived cardiac cells.

  • Methods
  • Methods

    Methods:

    • Kinase and phosphatase activity assays
    • western immunoblotting
    • immunofluorescence and confocal microscopy
    • proximity ligation assays
    • protein expression and purification
    • protein-protein interaction assays
    • analysis of oxidative post-translational modifications
    • gene expression analysis
    • primary cell cultures
    • cell line cultures
    • macrophage function
    • CRISPR Cas9-genome editing and hiPSC differentiation to cardiomyocytes and vascular smooth muscle cells (see relevant Figure)

  • Publications:

    1. Cuello F, Herberg FW, Stathopoulou K, Henning P, Diering S. Regulation of cardiac PKA signalling by cAMP and oxidants. Antioxidants in press. doi: org/10.3390/ antiox10050663

    2. Cuello F, Knaust A, Saleem U, Loos M, Raabe J, Mosqueira D, Laufer S, Schweizer M, Van der Kraak P, 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. Impairment of the ER/mitochondria compartment in human cardiomyocytes with PLN p.Argdel14 mutation. EMBO Mol Med in press. doi: 10.15252/emmm.20201307

    3. Rhoden A, Friedrich FW, Brandt T, Raabe J, Schweizer M, Meisterknecht J, Wittig I, Ulmer BM, Klampe B, Uebeler J, Piasecki A, Lorenz K, Eschenhagen T, Hansen A, Cuello F. Sulforaphane exposure impairs contractility and mitochondrial function in three-dimensional engineered heart tissue. Redox Biol. 2021; 41:101951. doi: 10.1016/j.redox.2021.101951

    4. Burnap SA, Mayr U, Shankar-Hari M, Cuello F, Thomas MR, Shah AM, Sabroe I, Storey RF, Mayr M. A Proteomics-Based Assessment of Inflammation Signatures in Endotoxemia. Mol Cell Proteomics. 2021 Feb 24;20:100021. doi: 10.1074/mcp.RA120.002305. Epub ahead of print. PMID: 33288685; PMCID: PMC7950208.

    5. Diering S, Stathopoulou K, Goetz M, Rathjens L, Harder S, Piasecki A, Raabe J, Schulz S, Brandt M, Pflaumenbaum J, Fuchs U, Donzelli S, Sadayappan S, Nikolaev VO, Flenner F, Ehler E, Cuello F. Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents. J Biol Chem. 2020 Nov 6;295(45):15342-15365. doi: 10.1074/jbc.RA120.014467. Epub 2020 Aug 31. PMID: 32868295; PMCID: PMC7650233.

    6. Tomasovic A, Brand T, Schanbacher C, Kramer S, Hümmert MW, Godoy P, Schmidt-Heck W, Nordbeck P, Ludwig J, Homann S, Wiegering A, Shaykhutdinov T, Kratz C, Knüchel R, Müller-Hermelink HK, Rosenwald A, Frey N, Eichler J, Dobrev D, El-Armouche A, Hengstler JG, Müller OJ, Hinrichs K, Cuello F, Zernecke A, Lorenz K. Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects. Nat Commun. 2020 Apr 7;11(1):1733. doi: 10.1038/s41467-020-15505-4. PMID: 32265441; PMCID: PMC7138859.

    7. Cuello F, Nikolaev VO. Cardiac cGMP Signaling in Health and Disease: Location, Location, Location. J Cardiovasc Pharmacol. 2020 May;75(5):399-409. doi: 10.1097/FJC.0000000000000802. PMID: 32040034.

    8. Stathopoulou K, Schobesberger S, Bork NI, Sprenger JU, Perera RK, Sotoud H, Geertz B, David JP, Christ T, Nikolaev VO, Cuello F. Divergent off-target effects of RSK N-terminal and C-terminal kinase inhibitors in cardiac myocytes. Cell Signal. 2019 Nov;63:109362. doi: 10.1016/j.cellsig.2019.109362. Epub 2019 Jul 22. PMID: 31344438.

    9. Schaefer A, Schneeberger Y, Schulz S, Krasemann S, Werner T, Piasecki A, Höppner G, Müller C, Morhenn K, Lorenz K, Wieczorek D, Schwoerer AP, Eschenhagen T, Ehmke H, Reichenspurner H, Stenzig J, Cuello F. Analysis of fibrosis in control or pressure overloaded rat hearts after mechanical unloading by heterotopic heart transplantation. Sci Rep. 2019 Apr 5;9(1):5710. doi: 10.1038/s41598-019-42263-1. PMID: 30952943; PMCID: PMC6451012.

    10. Cuello F, Eaton P. Cysteine-Based Redox Sensing and Its Role in Signaling by Cyclic Nu cleotide-Dependent Kinases in the Cardiovascular System. Annu Rev Physiol. 2019 Feb 10;81:63-87. doi: 10.1146/annurev-physiol-020518-114417. Epub 2018 Sep 14. PMID: 30216743.

    11. Cuello F, Wittig I, Lorenz K, Eaton P. Oxidation of cardiac myofilament proteins: Priming for dysfunction? Mol Aspects Med. 2018 Oct;63:47-58. doi: 10.1016/j.mam.2018.08.003. Epub 2018 Aug 23. PMID: 30130564.

    12. Donzelli S, Goetz M, Schmidt K, Wolters M, Stathopoulou K, Diering S, Prysyazhna O, Polat V, Scotcher J, Dees C, Subramanian H, Butt E, Kamynina A, Schobesberger S, King SB, Nikolaev VO, de Wit C, Leichert LI, Feil R, Eaton P, Cuello F. Oxidant sensor in the cGMP-binding pocket of PKGIα regulates nitroxyl-mediated kinase activity. Sci Rep. 2017 Aug 30;7(1):9938. doi: 10.1038/s41598-017-09275-1. PMID: 28855531; PMCID: PMC5577323.

    13. Scotcher J, Prysyazhna O, Boguslavskyi A, Kistamas K, Hadgraft N, Martin ED, Worthington J, Rudyk O, Rodriguez Cutillas P, Cuello F, Shattock MJ, Marber MS, Conte MR, Greenstein A, Greensmith DJ, Venetucci L, Timms JF, Eaton P. Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response. Nat Commun. 2016 Oct 26;7:13187. doi: 10.1038/ncomms13187. PMID: 27782102; PMCID: PMC5095173.

    14. Cuello F, Lorenz K. Inhibition of cardiac CaMKII to cure heart failure: step by step towards translation? Basic Res Cardiol. 2016 Nov;111(6):66. doi: 10.1007/s00395-016-0582-1. Epub 2016 Sep 28. PMID: 27683175; PMCID: PMC5040741.

    15. Jacob F, Yonis AY, Cuello F, Luther P, Schulze T, Eder A, Streichert T, Mannhardt I, Hirt MN, Schaaf S, Stenzig J, Force T, Eschenhagen T, Hansen A. Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue. PLoS One. 2016 Feb 3;11(2):e0145937. doi: 10.1371/journal.pone.0145937. Erratum in: PLoS One. 2018 Nov 27;13(11):e0208342. PMID: 26840448; PMCID: PMC4740402.

    16. Stathopoulou K, Wittig I, Heidler J, Piasecki A, Richter F, Diering S, van der Velden J, Buck F, Donzelli S, Schröder E, Wijnker PJ, Voigt N, Dobrev D, Sadayappan S, Eschenhagen T, Carrier L, Eaton P, Cuello F. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure. FASEB J. 2016 May;30(5):1849-64. doi: 10.1096/fj.201500048. Epub 2016 Feb 2. PMID: 26839380; PMCID: PMC4836368.

    17. Flenner F, Friedrich FW, Ungeheuer N, Christ T, Geertz B, Reischmann S, Wagner S, Stathopoulou K, Söhren KD, Weinberger F, Schwedhelm E, Cuello F, Maier LS, Eschenhagen T, Carrier L. Ranolazine antagonizes catecholamine-induced dysfunction in isolated cardiomyocytes, but lacks long-term therapeutic effects in vivo in a mouse model of hypertrophic cardiomyopathy. Cardiovasc Res. 2016 Jan 1;109(1):90-102. doi: 10.1093/cvr/cvv247. Epub 2015 Nov 3. PMID: 26531128.

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