Molecular Biology of Cell Growth

Our research

Our research in the field of experimental molecular cardiology is motivated by the overall goal to establish new therapeutic concepts for the prevention and treatment of heart failure.

We are an enthusiastic team working together on mRNA-binding proteins, mRNA modifications, regulatory structural elements of mRNAs, and on comprehensive characterization of disease causing genes and protein complexes.

Based on our experiments we aim to develop new therapeutic and diagnostic principles, using mRNA as therapeutic or by targeting mRNA translation. Close interactions with pre-clinical and clinical departments of the University Hospital Heidelberg, local (Heidelberg University, EMBL), national (e.g. DZHK partner sites) and international partners help us in an interdisciplinary approach to identify molecular mechanisms and design future therapeutic possibilities.

Projects

1. MTORC1

Characterization of mTOR signaling in the heart

One important aspect of the molecular remodeling process in heart failure are changes of the myocardial energy metabolism. Substrate utilization of the heart is generally dysregulated in HF and is characterized by changes in multiple metabolic substrates, including FAs, amino acids, ketones, and glucose. A nodal point of anabolism, glucose and lipid metabolism is the nutrient-sensing mechanistic Target Of Rapamycin Complex 1 (mTORC1), an conserved kinase complex. mTORC1 activation controls translational of specific networks of mRNAs that are required to stress adaptation and metabolic remodeling. Since inhibition of mTORC1 in cardiomyocytes is protective against the development of HF, suggesting that mTORC1 could be a promising molecular target for treatment of HF, our studies aim to comprehensively characterize mTORC1-dependent signaling on translational control, metabolism and cardiac function in different cardiac cells.

Publications:

Transient Inhibition of Translation Improves Cardiac Function After Ischemia/Reperfusion by Attenuating the Inflammatory Response
Christoph Hofmann, Adrian Serafin, Ole M. Schwerdt, Johannes Fischer, Florian Sicklinger, Fereshteh S. Younesi, Nikole J. Byrne, Ingmar S. Meyer, Ellen Malovrh, Clara Sandmann, Lonny Jürgensen, Verena Kamuf-Schenk, Claudia Stroh, Zoe Löwenthal, Daniel Finke, Etienne Boileau, Arica Beisaw, Heiko Bugger, Mandy Rettel, Frank Stein, Hugo A. Katus, Tobias Jakobi, Norbert Frey, Florian Leuschner, Mirko Völkers
Circulation, 2024 Aug

Translational control of Ybx1 expression regulates cardiac function in response to pressure overload in vivo
Eshita Varma, Jana Burghaus, Thomas Schwarzl, Thileepan Sekaran, Parul Gupta, Agnieszka A. Górska, Christoph Hofmann, Claudia Stroh, Lonny Jürgensen, Verena Kamuf-Schenk, Xue Li, Rebekka Medert, Florian Leuschner, Vivien Kmietczyk, Marc Freichel, Hugo A. Katus, Matthias W. Hentze, Norbert Frey, Mirko Völkers
Basic Research in Cardiology, vol. 118, 2023 Jun, p. 25

Muscle-specific Cand2 is translationally upregulated by mTORC1 and promotes adverse cardiac remodeling
Agnieszka A. Górska, Clara Sandmann, Eva Riechert, Christoph Hofmann, Ellen Malovrh, Eshita Varma, Vivien Kmietczyk, Julie Ölschläger, Lonny Jürgensen, Verena Kamuf-Schenk, Claudia Stroh, Jennifer Furkel, Mathias H. Konstandin, Carsten Sticht, Etienne Boileau, Christoph Dieterich, Norbert Frey, Hugo A. Katus, Shirin Doroudgar, Mirko Völkers
EMBO reports, vol. 22, 2021 Dec, pp. e52170

PRAS40 suppresses atherogenesis through inhibition of mTORC1-dependent pro-inflammatory signaling in endothelial cells
Kevin Sun Zhang, Johannes Schecker, Alexandros Krull, Eva Riechert, Lonny Jürgensen, Verena Kamuf-Schenk, Jana Burghaus, Leon Kiper, Thanh Cao Ho, Kerstin Wöltje, Verena Stangl, Hugo A. Katus, Karl Stangl, Mirko Völkers, Till F. Althoff
Scientific Reports, vol. 9, 2019 Nov, p. 16787

2. RNA BINDING PROTEINS

Riboregulation in cardiomyocytes

Several of our projects try to elucidate how RNA binding proteins (RBPs) are involved in pathological processes that lead to heart failure by affecting the gene expression of cardiomyocytes. We aim to identify novel RBPs in cardiomyocytes and are interested in the pathways that lead to changes in the binding behaviors of the RBPs. We are also interested in so called unconventional RNA-binding proteins, which often lack classical RNA-binding domains and aim to address the effect of RNA binding (‘riboregulation’) on established aspects of the protein functions.

Publications:

RNA-binding proteins in cardiovascular biology and disease: the beat goes on
Mirko Völkers, Thomas Preiss, Matthias W. Hentze
Nature Reviews Cardiology, vol. 21, 2024 Jun, pp. 361--378

Ythdf2 regulates cardiac remodeling through its mRNA target transcripts
V. Kmietczyk, J. Oelschläger, P. Gupta, E. Varma, S. Hartl, J. Furkel, M. Konstandin, A. Marx, Z. Loewenthal, V. Kamuf-Schenk, L. Jürgensen, C. Stroh, A. Gorska, A. Martin-Garrido, J. Heineke, T. Jakobi, N. Frey, M. Völkers
Journal of Molecular and Cellular Cardiology, vol. 181, 2023 Aug, pp. 57—66

Identification of dynamic RNA-binding proteins uncovers a Cpeb4-controlled regulatory cascade during pathological cell growth of cardiomyocytes
Eva Riechert, Vivien Kmietczyk, Frank Stein, Thomas Schwarzl, Thileepan Sekaran, Lonny Jürgensen, Verena Kamuf-Schenk, Eshita Varma, Christoph Hofmann, Mandy Rettel, Kira Gür, Julie Ölschläger, Friederike Kühl, Judit Martin, Marta Ramirez-Pedraza, Mercedes Fernandez, Shirin Doroudgar, Raúl Méndez, Hugo A. Katus, Matthias W. Hentze, Mirko Völkers
Cell Reports, vol. 35, 2021 May, p. 109100

3. MRNA METABOLISM

Developing molecular therapies

By using high-throughput technologies such as Ribosomal-sequencing and other (RNA based) sequencing techniques we aim to identify new pathways and target genes that drive the development of heart failure, cardiac remodeling and hypertrophy with the overall goal to develop molecular therapies. Using transcriptome and translatome mapping approaches we also study new, cardiac, (small) open reading frames (ORFs), their putative peptides and their potential regulatory role in cardiomyocytes and other cardiac cells.

Publications:

RNA-binding proteins in cardiovascular biology and disease: the beat goes on
Mirko Völkers, Thomas Preiss, Matthias W. Hentze
Nature Reviews Cardiology, vol. 21, 2024 Jun, pp. 361--378

Dynamic interplay between RPL3- and RPL3L-containing ribosomes modulates mitochondrial activity in the mammalian heart
Ivan Milenkovic, Helaine Graziele Santos Vieira, Morghan C. Lucas, Jorge Ruiz-Orera, Giannino Patone, Scott Kesteven, Jianxin Wu, Michael Feneley, Guadalupe Espadas, Eduard Sabidó, Norbert Hübner, Sebastiaan van Heesch, Mirko Völkers, Eva Maria Novoa
Nucleic Acids Research, vol. 51, 2023 Jun, pp. 5301--5324

TIP30 counteracts cardiac hypertrophy and failure by inhibiting translational elongation
Andrea Grund, Malgorzata Szaroszyk, Mortimer Korf-Klingebiel, Mona Malek Mohammadi, Felix A Trogisch, Ulrike Schrameck, Anna Gigina, Christopher Tiedje, Matthias Gaestel, Theresia Kraft, Jan Hegermann, Sandor Batkai, Thomas Thum, Andreas Perrot, Cris dos Remedios, Eva Riechert, Mirko Völkers, Shirin Doroudgar, Andreas Jungmann, Ralf Bauer, Xiaoke Yin, Manuel Mayr, Kai C Wollert, Andreas Pich, Hua Xiao, Hugo A Katus, Johann Bauersachs, Oliver J Müller, Joerg Heineke
EMBO Molecular Medicine, vol. 11, 2019 Oct, pp. e10018

Monitoring Cell-Type-Specific Gene Expression Using Ribosome Profiling In Vivo During Cardiac Hemodynamic Stress
Shirin Doroudgar, Christoph Hofmann, Etienne Boileau, Brandon Malone, Eva Riechert, Agnieszka A. Gorska, Tobias Jakobi, Clara Sandmann, Lonny Jürgensen, Vivien Kmietczyk, Ellen Malovrh, Jana Burghaus, Mandy Rettel, Frank Stein, Fereshteh Younesi, Ulrike A. Friedrich, Victoria Mauz, Johannes Backs, Günter Kramer, Hugo A. Katus, Christoph Dieterich, Mirko Völkers
Circulation Research, vol. 125, 2019 Aug, pp. 431--448

m6A-mRNA methylation regulates cardiac gene expression and cellular growth
Vivien Kmietczyk, Eva Riechert, Laura Kalinski, Etienne Boileau, Ellen Malovrh, Brandon Malone, Agnieszka Gorska, Christoph Hofmann, Eshita Varma, Lonny Jürgensen, Verena Kamuf-Schenk, Janine Altmüller, Rewati Tappu, Martin Busch, Patrick Most, Hugo A. Katus, Christoph Dieterich, Mirko Völkers
Life Science Alliance, vol. 2, 2019 Apr

Arbeitsgruppenleiter

Dr. med. Mirko Völkers

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Postdocs

Dr. rer. nat. Maja Bencun
Dr. rer. nat. Vivien Kmietczyk

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Research Technician

Lonny Jürgensen

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06221 56-38231
Verena Kamuf-Schenk

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06221 56-32789

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Zoe Löwenthal

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06221 56-38231
Laura Spreyer

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06221 56-311704
Claudia Stroh

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06221 56-35608

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Doktoranden/-innen

Eva Batke
Dimitrios Destounis
Johannes Fischer
Parul Gupta
Christoph Hofmann

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Jannis Kreft
Patrizia Kühne
Mariam Rogge
Paul Sigrist

Auszubildende

Vanessa Beisel

Alumnae und Alumni

Lena Antes
Dr. med. Jana Burghaus-Zhang

Ärztliche Leitung Phlebologie und Proktologie

Schwerpunkt

Phlebochirurgie
Operative Dermatologie
Aga Górska

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Candelas Groß Valle
Kira Gür
Than Cao Ho

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Moritz Kern
Leon Kiper

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Ellen Malovrh

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Clara Sandmann
Ayse Sanlialp

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Carolyn Schneider
Sophia Siegmund
Eshita Varma
Laura Wiegand
Fereshteh Younesi
Kevin Zhang

Fundings

We gratefully acknowledge funding from current and previous sources.

Collaborators

Dr. Shirin Doroudgar
Prof. Christoph Diederich
Prof. Dr. Bernd Bukau
Prof. Dr. Johannes Backs
Dr. Mathias Konstandin

Prof. Dr. Oliver Friedrich, Universität Erlangen

Prof. Dr. Mark Sussman, San Diego State University Heart Institute, San Diego, California, USA
Prof. Dr. Chris Glembotski, San Diego State University Heart Institute, San Diego, California, USA

Vacancies - Jobs and Doctoral Theses

We regularly seek highly motivated candidates. Please contact Mr. Völkers (head of research group) or Lonny Jürgensen (Lab manager/Research technician).

Forschung