Developmental Pharmacology

Principal Investigator:

Priv.-Doz. Dr. rer. nat. Laura Zelarayan

About Us

The cardiac Wnt-complex in the developing, healthy and diseased heart

Heart failure is characterized by an imbalanced myocardial damage and repair. Understanding the mechanisms causing progressive damage and halting repair will be the basis to develop new therapeutic concepts for preventing heart failure progression. Based on several data indicating that modulation of Wnt/β-catenin signaling may be instrumental in cardiac function preservation and regenerative strategies, we aim to unravel Wnt-dependent factors and mechanisms instructing cardiac tissue formation, heart homeostasis and remodeling in a cell specific manner.

Our main current topics include:
(I) Krueppel-like factor (KLF) 15-Wnt dynamics in homeostasis and remodeling of the mouse and human myocardial tissue;
(II) the role of Wnt-related factors for endothelial cell homeostasis of the fetal and diseased heart;
(III) the epigenetic role of TCF7L2 on Wnt/β-catenin mediated activation in the regenerative and diseased heart;
(IV) the Wnt-exosome mediated signaling in the adult heart and its cellular cross-talk;
(V) the role of novel cardiac Wnt components in cardiogenesis and,
(VI) the characterization of cardiomyocytes secreted protein in heart failure.

This knowledge will contribute to the understanding of cardiac specific Wnt-dependent mechanisms essential for heart homeostasis with special emphasis of mechanisms conserved in human tissue.


β-catenin/TCF7L2 transcriptional activation induces TCF7L2 and H3K27ac recruitment to disease-associated enhancers and results in increased developmental processes, cardiomyocytes cell cycling and cytoskeletal remodeling in the adult heart. doi: 10.1093/nar/gky049


Our methodology is based on biochemical, epigenetic, transcriptional and functional investigation of novel identified factors using classical mouse knockout strategies combined with embryo culture and tissue explants as well as CRISPR/Cas9-based technology for gene targeting (knockout and gene activation) in vitro in human stem cells and in vivo in the mouse


Mouse embryo (day 9.5) cultured after electroporation with a GFP expressing plasmid into the developing heart tube.



Selected Publications

  • Iyer LM, Nagarajan S, Woelfer M, Schoger E, Khadjeh S, Zafiriou MP, Kari V, Herting J, Pang ST, Weber T, Rathjens FS, Fischer TH, Toischer K, Hasenfuss G, Noack C, Johnsen SA, Zelarayán LC. A context-specific cardiac β-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart. Nucleic Acids Res. 2018 Jan 31. doi: 10.1093/nar/gky049. [Epub ahead of print] PubMed PMID: 29394407.

  • Noack C, Haupt LP, Zimmermann WH, Streckfuss-Bömeke K, Zelarayán LC. Generation of a KLF15 homozygous knockout human embryonic stem cell line using paired CRISPR/Cas9n, and human cardiomyocytes derivation. Stem Cell Res. 2017 Aug;23:127-131. doi: 10.1016/j.scr.2017.07.007. Epub 2017 Jul 11. PubMed PMID: 28925362.

  • Zafiriou MP, Noack C, Unsold B, Didie M, Pavlova E, Fischer HJ, Reichardt HM, Bergmann MW, El-Armouche A, Zimmermann WH, Zelarayan LC. (2014) Erythropoietin responsive cardiomyogenic cells contribute to heart repair post myocardial infarction. Stem cells. 2014;32:2480-2491. [PubMed]

  • Renger A, Zafiriou MP, Noack C, Pavlova E, Becker A, Sharkova K, Bergmann MW, El-Armouche A, Zimmermann WH, Zelarayán LC. The four and a half LIM-domain 2 controls early cardiac cell commitment and expansion via regulating β-catenin-dependent transcription. Stem Cells. 2013 May;31(5):928-40. doi: 10.1002/stem.1332. PubMed PMID: 23341242.

  • Noack C, Zafiriou MP, Schaeffer HJ, Renger A, Pavlova E, Dietz R, Zimmermann WH, Bergmann MW, Zelarayan LC. (2012) Krueppel-like factor 15 regulates Wnt/beta-catenin transcription and controls cardiac progenitor cell fate in the postnatal heart. EMBO Mol Med 4(9): 992-1007. [PubMed]
  • Contact details


      Priv.-Doz. Dr. rer. nat. Laura Zelarayan

      Institute of Pharmacology and Toxicology,
      University Medical Center Goettingen,
      Robert-Koch-Str. 40, 37075 Goettingen, Germany
      Tel: +49 (0) 551 39-20730
      Fax: +49 (0) 551 39-5699

      E-mail Curriculum Vitae

    Staff


    Dr. Maria-Patapia Zafeiriou
    Postdoctoral Scientist

    Main Building
    Tel: +49 (0) 551 39-5777


    Ms. Lavanya M. Iyer
    PhD Student

    Main Building
    Tel: +49 (0) 551 39-5775


    Ms. Sze Ting Pang
    Masters Student

    Main Building
    Tel: +49 (0) 551 39-5775


    Ms. Franziska Rathjens
    PhD Student

    Main Building
    Tel: +49 (0) 551 39-5779


    Mr. Eric Schoger
    PhD Student

    Main Building
    Tel: +49 (0) 551 39-5779


    Mr. Tobias Weber
    MD Student

    Main Building
    Tel: +49 (0) 551 39-10816


    Ms. Monique Woelfer
    PhD Student

    Main Building
    Tel: +49 (0) 551 39-5779