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The Group for Cardiopulmonary and Metabolic Interactions (AG Legchenko)

The AG Legchenko investigates the molecular mechanisms underlying right ventricular (RV) failure, with a particular focus on pressure overload both with and without the development of pulmonary hypertension (PAH). Using preclinical models, patient-derived data, and multi-omics approaches, we aim to define how the molecular, cellular and metabolic interactions during pressure overload impact the dynamic interplay between cardiomyocytes, fibroblasts, and endothelial cells in the right ventricle as well as between both ventricles.

Our overarching goal is to apply targeted genetic and metabolic strategies to improve right ventricular function in disease.

We are currently pursuing two main research directions:

  1. P5-ATPases and Polyamine Metabolism in Cardiac Stress
    We study the role of P5-ATPases in cardiac cells and how modulation of polyamine metabolism may benefit the failing heart. Using novel genetic models and multi-omics approaches, we aim to identify targetable pathways and propose innovative therapeutic strategies.
  2. Reversibility of Pathologic Cardiac Fibrosis
    We explore whether maladaptive cardiac fibrosis can be reversed. Specifically, we investigate how cardiac fibroblasts respond to altered pressure conditions and assess whether these responses can be therapeutically modulated and translated into clinical application.

Our group integrates in vivo and in vitro models with advanced multi-omics and bioinformatics to delineate cell-specific responses and intercellular crosstalk in the stressed right heart and the multi-organ interplay.

People

Dr. Ekaterina Legchenko

Group Leader
Ekaterina studied Applied Mathematics and Physics from 2007 to 2011, before completing a Master of Science in Molecular Biophysics (2011–2013). She earned her PhD in Molecular Medicine in 2017 from Hannover Medical School. In 2018, she joined the Department of Medicine at the University of Cambridge as a postdoctoral fellow, where she secured a RESPIRE3 Marie Skłodowska-Curie Fellowship. In 2022, she was appointed Junior Group Leader at the Department of Cardiovascular Physiology, Medical Faculty Mannheim, Heidelberg University. She serves as Scientist in the German Center of Cardiovascular Research (DZHK, Partner site Heidelberg/Mannheim).

Jennifer Schöning

Senior Technical Assistant & Laboratory Manager
Jennifer completed her training as a biology laboratory assistant in Hannover in 2007. Since then, she has gained extensive professional experience at the Helmholtz Centre for Infection Research in Braunschweig, Hannover Medical School, and University Hospital Würzburg. In 2025, she joined the Legchenko group in Mannheim, where she also serves as laboratory manager.

 

Merle Johanna Cremer

Medical Student & MD Thesis Researcher
Merle is a medical student at the Medical Faculty Mannheim. In 2023–2024, she took a dedicated research year supported by a faculty stipend to complete her MD thesis in the Legchenko group. Her work focused on the role of Sox9 in orchestrating the metabolic switch of activated cardiac fibroblasts.

Funding

The Group for Cardiopulmonary and Metabolic Interactions gratefully acknowledges generous support from the Medical Faculty Mannheim, the German Research Foundation (DFG), and the Else Kröner-Fresenius-Stiftung.

Selected Publications

  • Legchenko E, Chouvarine P, Hysko K, Qadri F, Wesolowski R, Specker E, Glage S, Meier M, Schwarz K, Heineke J, Pohlmann G, Ramazanoglu M, Bader M, Hansmann G. Inhalation of the Novel Tryptophan Hydroxylase 1 Inhibitor TPT-004 Alleviates Pulmonary Arterial Hypertension. Am J Respir Cell Mol Biol. 2025 Feb 3. doi: 10.1165/rcmb.2024-0365OC. 
  • Legchenko E, Chouvarine P, Qadri F, Specker E, Nazaré M, Wesolowski R, Matthes S, Bader M, Hansmann G. Novel Tryptophan Hydroxylase Inhibitor TPT-001 Reverses PAH, Vascular Remodeling, and Proliferative-Proinflammatory Gene Expression. JACC Basic Transl Sci. 2024 Jun 5;9(7):890-902. doi: 10.1016/j.jacbts.2024.04.006.
  • Liu B*, Azfar M*, Legchenko E*, West JA, Martin S, Van den Haute C, Baekelandt V, Wharton J, Howard L, Wilkins MR, Vangheluwe P, Morrell NW, Upton PD. ATP13A3 variants promote pulmonary arterial hypertension by disrupting polyamine transport. Cardiovasc Res. 2024 May 29;120(7):756-768. doi: 10.1093/cvr/cvae068. 
  • Hamberger F*, Legchenko E*, Chouvarine P, Mederacke YS, Taubert R, Meier M, Jonigk D, Hansmann G, Mederacke I. Pulmonary Arterial Hypertension and Consecutive Right Heart Failure Lead to Liver Fibrosis. Front Cardiovasc Med. 2022 Mar 17;9:862330. doi: 10.3389/fcvm.2022.862330.
  • Chouvarine P, Legchenko E, Geldner J, Riehle C, Hansmann G. Hypoxia drives cardiac miRNAs and inflammation in the right and left ventricle. J Mol Med (Berl). 2019 Oct;97(10):1427-1438. doi: 10.1007/s00109-019-01817-6. 
  • Legchenko E, Chouvarine P, Borchert P, Fernandez-Gonzalez A, Snay E, Meier M, Maegel L, Mitsialis SA, Rog-Zielinska EA, Kourembanas S, Jonigk D, Hansmann G. PPARγ agonist pioglitazone reverses pulmonary hypertension and prevents right heart failure via fatty acid oxidation. Sci Transl Med. 2018 Apr 25;10(438):eaao0303. doi: 10.1126/scitranslmed.aao0303. 
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