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Department for Internal Medicine II
Cardiology, Pneumology, Internal Intensive Care Medicine

Lab Prof. Lebek

Experimental Cardiology and Gene Editing

Cardiovascular diseases are the main cause of morbidity and mortality worldwide, highlighting the need for new therapeutic strategies. We are investigating numerous cardiovascular disease models (including cell models, genetic and surgical mouse models, and actual patient biomaterial) to decipher pathomechanisms and identify potentially modifiable disease effectors. We are designing gene therapy and editing approaches in vitro in cells. The strategies are further optimized in human stem cells, which can be differentiated into various tissues. Before moving to in vivo models, we are thoroughly characterizing each individual approach with state-of-the-art methodologies, including patch clamp technique and live-cell imaging with epifluorescence/confocal laser scanning microscopy. The most promising gene therapy/editing strategies are further pursued in in vivo models of cardiovascular diseases, and therapeutic benefits are tested using echocardiography, electrophysiological studies with cardiac catheterization, and telemetry. We are also collaborating with the Department of Cardiothoracic Surgery, enabling us to deploy optimized therapeutic strategies in actual patient samples.

  • Team
    • Prof. Dr. Simon Lebek
    • Dr. Philipp Hegner
    • Dr. Sönke Schildt
    • Anna-Maria Lauerer, M.Sc.
    • Yanzhu Hu, M.Sc.
    • Fatma Bayram
    • Bettina Seydel
    • Dominik Wermers
    • Benedikt Schaner
    • Jonas Rohde
    • Fredrik Bassermann
    • Lukas Welsch

  • Top 10 Publications
    • Lauerer AM, Caravia XM, Maier LS, Chemello F, Lebek S. Gene editing in common cardiovascular diseases. Pharmacol Ther 2024; 263: 108720. DOI: 10.1016/j.pharmthera.2024.108720 (IF: 12.0)
    • Hegner P, Ofner F, Schaner B, Gugg M, Trum M, Lauerer A-M, Maier LS, Arzt M, Lebek S#, Wagner S#. CaMKIIδ-dependent dysregulation of atrial Na+ homeostasis promotes pro-arrhythmic activity in an obstructive sleep apnea mouse model. Front Pharmacol 2024; 15: 1411822. DOI: 10.3389/fphar.2024.1411822 (IF: 4.4) # – shared last-authorship
    • Hegner P, Wester M, Tafelmeier M, Provaznik Z, Klatt S, Schmid C, Maier LS, Arzt M, Wagner S#, Lebek S#. Systemic inflammation predicts diastolic dysfunction in patients with sleep disordered breathing. Eur Respir J 2024; 63: 2400579. DOI: 10.1183/13993003.00579-2024 (IF: 16.6)
    • Lebek S, Caravia XM, Straub LG, Alzhanov D, Tan W, Li H, McAnally JR, Chen K, Xu L, Scherer PE, Liu N, Bassel-Duby R, Olson EN. CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model. J Clin Invest 2024; 134: e175164. DOI: 10.1172/JCI175164 (IF: 13.3)
    • Lebek S, Caravia XM, Chemello F, Tan W, McAnally JR, Chen K, Xu L, Liu N, Bassel-Duby R, Olson EN. Elimination of CaMKIIδ Autophosphorylation by CRISPR-Cas9 Base Editing Improves Survival and Cardiac Function in Heart Failure in Mice. Circulation 2023; 148: 1490–1504. DOI: 10.1161/CIRCULATIONAHA.123.065117 (IF: 35.5)
    • Lebek S, Chemello F, Caravia XM, Tan W, Li H, Chen K, Xu L, Liu N, Bassel-Duby R, Olson EN. Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease. Science 2023; 379: 179–185. DOI: 10.1126/science.ade1105 (IF: 44.7)
    • Lebek S*, Hegner P*, Hultsch R, Rohde J, Rupprecht L, Schmid C, Sossalla S, Maier LS, Arzt M, Wagner S. Voltage-Gated Sodium Channel NaV1.8 Dysregulates Na and Ca, Leading to Arrhythmias in Patients with Sleep-Disordered Breathing. Am J Respir Crit Care Med 2022; 206: 1428–1431. DOI: 10.1164/rccm.202205-0981LE (IF: 24.7) * – shared first-authorship
    • Lebek S, Pichler K, Reuthner K, Trum M, Tafelmeier M, Mustroph J, Camboni D, Rupprecht L, Schmid C, Maier LS, Arzt M, Wagner S. Enhanced CaMKII-Dependent Late INa Induces Atrial Proarrhythmic Activity in Patients With Sleep-Disordered Breathing. Circ Res 2020; 126: 603–615. DOI: 10.1161/CIRCRESAHA.119.315755 (IF: 17.4)
    • Lebek S, Tafelmeier M, Messmann R, Provaznik Z, Schmid C, Maier LS, Birner C, Arzt M, Wagner S. Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment and haemodynamic factors are associated with increased cardiac mRNA expression of angiotensin-converting enzyme 2 in patients with cardiovascular disease. Eur J Heart Fail 2020; 22: 2248–2257. DOI: 10.1002/ejhf.2020 (IF: 15.5)
    • Lebek S, Plößl A, Baier M, Mustroph J, Tarnowski D, Lücht CM, Schopka S, Flörchinger B, Schmid C, Zausig Y, Pagratis N, Marchand B, Koltun DO, Hung WK, Ahmadyar S, Belardinelli L, Maier LS, Wagner S. The novel CaMKII inhibitor GS-680 reduces diastolic SR Ca leak and prevents CaMKII-dependent pro-arrhythmic activity. J Mol Cell Cardiol 2018; 118: 159–168. DOI: 10.1016/j.yjmcc.2018.03.020 (IF: 5.1)

    Further publications can be found on the website of the National Library of Medicine.

     

Contact

[Translate to englisch:] ©Julia Dragan/UR

Lab Leader

Prof. Dr. Simon Lebek, FESC

W2 Heisenberg-Professor of Internal Medicine, Experimental Cardiology, and Gene Editing


+49941 944-17973 simon.lebek@ukr.de