UKE Homepage
DE
Research Group Carrier
Functional Genomics of Cardiomyopathies
Aim
We aim at deciphering the contribution of microtubule modifications and autophagy-lysosomal pathway alterations in inherited cardiomyopathies and to test therapeutic options.
Scope of Research
Cardiomyopathy • Sarcomere • Microtubules • Therapy
Research Projects
Main Questions
- Do sarcomeric mutations alter the contractile and electrophysiological phenotype of human induced-pluripotent stem cell (iPSC)-derived cardiomyocytes and engineered heart tissues (EHTs)? Can we specifically target functional alterations with drug- and nucleic acid-therapy as personalised medicine?
- Do human iPSC-derived cellular models of modified microtubules develop functional alterations in EHTs?
- What is the impact of modified microtubules on the transport of autophagosomes, lysosomes and mitochondria? Can we improve autophagic flux and/or proteasomal activities by targeting microtubule modifications? What is the impact of targeting microtubule modifications in mouse and human cellular models of hypertrophic cardiomyopathy?
Current Projects
1. Evaluation of modified microtubules on cardiomyocyte cell proliferation
2. Evaluation of modified microtubules on autophagy-lysosomal pathway
3. Evaluation of cGMP-PRKG1 pathway on microtubule modifications
Key Techniques
- Disease modelling with CRISPR/Cas9 technology in human induced pluripotent stem cell-derived cardiomyocytes and engineered heart tissues
- Evaluation of the function in cardiomyocytes, engineered heart tissue and mice (echocardiography)
- Live cell imaging and confocal microscopy
- Molecular biology
Group Members
Saskia Schlossarek,
PhD,
Senior scientist;
Niels Pietsch,
PhD,
Postdoctoral Research Fellow;
Moritz Meyer-Jens,
MSc,
PhD student;
Elisabeth Krämer,
MTA;
Maximilian Effenberg,
MD student;
Jarl Pirsing,
MD student;
Publications
-
Chronic activation of tubulin tyrosination improves heart function.
Pietsch N, Chen CY, Kupsch S, Bacmeister L, Geertz, B, Herrera-Rivero M, Siebels B, Voß H, Krämer E, Braren I, Westermann D, Schlüter H, Mearini G, Schlossarek S, van der Velden J, Caporizzo M, Lindner D, Prosser BL, Carrier L.
Circ Res (2024) Oct 11;135(9):910-932. doi: 10.1161/CIRCRESAHA.124.324387. -
Sacubitril/valsartan reduces proteasome activation and cardiomyocyte area in an experimental mouse model of hypertrophy
Meyer-Jens M*, Wenzel K*, Grube K, Rüdebusch J, Krämer E, Bahls M, Müller K, Voß H, Schlüter H, Felix SB, Carrier L, Könemann S#, Schlossarek S
J Mol Cell Cardiol Plus 7 (2024) 100050. doi: 10.1016/j.jmccpl.2023.100059 -
Translational investigation of electrophysiology in hypertrophic cardiomyopathy
Flenner F, Jungen C, Küpker N, Ibel A, Kruse M, Koivumäki JT, Rinas A, Zech ATL, Rhoden A, Wijnker PJM, Lemoine MD, Steenpass A, Girdauskas E, Eschenhagen T, Meyer C, van der Velden J, Patten-Hamel M, Christ T, Carrier L
J Mol Cell Cardiol. 2021 May 3;157:77-89. doi: 10.1016/j.yjmcc.2021.04.009. -
A high throughput screening identifies ZNF418 as a novel regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway.
Singh SR, Meyer-Jens M, Alizoti E, Bacon WC, Davis G, Osinska H, Gulick J, Reischmann-Düsener S, Orthey E, McLendon P, Molkentin JD, Schlossarek S, Robbins J, Carrier L
Autophagy 2021 17:3124-3139. doi: 10.1080/15548627.2020.1856493 -
Disease modeling of a mutation in a-actinin 2 guides clinical therapy in hypertrophic cardiomyopathy
Prondzynski M*, Lemoine MD*, Zech ATL, Horváth A, Di Mauro V, Koivumäki JT, Kresin N, Busch J, Krause T, Krämer E, Schlossarek S, Spohn M, Friedrich FW, Münch J, Laufer SD, Redwood C, Volk AE, Hansen A, Mearini G, Catalucci D, Meyer C, Christ T, Patten M, Eschenhagen T, Carrier L
EMBO Mol Med Dec 2019;11:e11115 DOI:10.15252/ emmm.201911115.
Grants/Awards
- 2021-2026
2021-2026 Leducq Foundation - Trans-Atlantic Network of Excellence “Cytoskeleton regulation in cardiomyocyte homeostasis in health and disease” – to Lucie Carrier – European coordinator - 2021-2025
German Center for Cardiovascular Research (DZHK) – Modeling pathomechanisms of cardiomyopathy in induced pluripotent stem cell-derived cardiac cells – to Lucie Carrier, co-Principal Investigator with Arne Hansen and Friederike Cuello (IEPT, UKE) - 2022-2025
DFG (CA 618/9-1) - Nichtinvasive Überwachung der hypertrophen Kardiomyopathie mittels MRT-basierter virtueller Herzbiopsie (cardiacMRBIOPSY) – to Lucie Carrier, co-Principal Investigator with Min-Chi Ku and Sonia Waiczies (MDC, Berlin) - 2025-2026
German Center for Cardiovascular Research (DZHK) – PostDoc Start-up Grant “Investigation of microtubule de-/tyrosination on cardiomyocyte proliferation” – to Niels Pietsch, Principal Investigator - 2025-2026
German Center for Cardiovascular Research (DZHK) – Shared Expertise Project “The role of increased calcium buffering in atrial arrhythmogenesis” – to Saskia Schlossarek in collaboration with Niels Voigt (Göttingen)
Honors
- Lucie Carrier: Received the Brutsaert Lecture of the Heart Failure Association of the ESC, February 2024
- Lucie Carrier: Co-chair elect of the GRC “Cardiac Regulatory Mechanisms”, New London, NH, USA, June 2024. Co-Chair in 2026.
- Maximilian Effenberg: Received a prestigious stipend from the „Jung-Stiftung für Wissenschaft und Forschung“, April 2024.
- Jarl Pirsig: Received a prestigious stipend from the „Werner Otto Stiftung“, November 2024.
- Moritz-Meyer-Jens: Elected co-chair for the next (2026) GRS “Cardiac Regulatory Mechanisms”, New London, NH, USA.
- Niels Pietsch: Nominated for the „Deutscher Studienpreis“, Körber-Stiftung, June 2025.
Patents
- Gene-therapy vectors for treating cardiomyopathy (EPA14719704, US20160108430, CA2944186), licensed to DiNAQOR AG
Most important collaboration partners
- Jolanda van der Velden, AMCU, Amsterdam, The Netherlands
- Benjamin Prosser, UPenn, Philadelphia, PA, USA
- Marie-Jo Moutin, GIN, Grenoble, France
- Izhak Kehat, Technion, Haifa, Israel