AG Konze
Cardiomyocytes from human induced pluripotent stem cells as a cellular model for hypertrophic cardiomyopathy
Research focus
The focus of our research is the analysis of human induced pluripotent stem cell (hiPSCs)-derived cardiomyocytes (hiPSC-CMs) carrying mutations in the cardiac myosin-binding protein C (cMyBP-C). Mutations in cMyBP-C are besides mutations in beta-cardiac myosin (MyHC) the most frequent genetic cause for hypertrophic cardiomyopathy (HCM). HCM is a severe disease of the heart, which is mostly characterised by thickening of the interventricular septum and the left ventricular wall. On the microscopic level, typically there is fibrosis and a loss of cardiomyocyte alignment (disarray). These alterations lead to progressive heart failure, but can also cause arrhythmias and sudden cardiac death.
In our group, we analyse in a DFG-funded project several hiPSCs with different mutations in cMyBP-C to achieve a better understanding of the molecular mechanisms leading to HCM. Our hypothesis is that unequal contractile properties of neighboring cardiomyocytes (“contractile imbalance”) lead or contribute to the development of disarray and fibrosis. Mechanisms that lead to contractile imbalance will be characterised here in a cellular model
The hiPSC-CMs are being generated with high purity in cooperation with the group of PD Dr. Robert Zweigerdt, LEBAO, MHH, and are further cultivated with our established maturation protocols to achieve a homogenous cardiomyocyte population with regard to different maturation markers, such as beta-MyHC. The matured cardiomyocytes are then screened for potential differences in gene expression, contractile features, calcium transients and alignment of myofibrils between hiPSCs-CMs with and without cMyBP-C mutations. We apply several state-of-the-art methods such as transcriptomics, MyoCam measurements, immunofluorescence microscopy and live cell microscopy.
Lab Members
- Tim Holler (MTLA)
- Uwe Krumm (FH)
- Birgit Piep (MTV/VMTA)
- Luqman Eljurnazi (Hiwi)
qulification work
- Sven Schwebe (Bachelor) 2024
Former members
- Dr. rer. nat. Meike Wendland
- Dr. med. Stephan Greten
- Dr. med. PhD. Natalie Weber
- Cand. med. Simon Schulte (StrukMed)
- Cand. med. Jan Nicolas Riesselmann (StrukMed)
- Cand med. Thomas Richard Saka Ikuye (StrukMed)
- Cand med. Noah R. Scheller (StrukMed)
- Osten, F., Weber, N., Wendland, M., Holler, T., Piep, B., Kröhn, S., Teske, J., Bodenschatz, A.K., Devadas, S.B., Menge, K.S., Chatterjee, S., Schwanke, K., Kosanke, M., Montag, J., Thum, T., Zweigerdt, R., Kraft, T., Iorga, B., and Meissner, J.D. (2023), Myosin expression and contractile function are altered by replating stem cell–derived cardiomyocytes, J Gen Physiol (2023) 155 (11): e202313377, https://doi.org/10.1085/jgp.202313377, Online ahead of print
- Halloin C, Schwanke K, Lobel W, Franke A, Szepes M, Biswanath S, Wunderlich S, Merkert S, Weber N, Osten F, de la Roche J, Polten F, Christoph Wollert K, Kraft T, Fischer M, Martin U, Gruh I, Kempf H, Zweigerdt R. Continuous WNT Control Enables Advanced hPSC Cardiac Processing and Prognostic Surface Marker Identification in Chemically Defined Suspension Culture. Stem cell reports. 2019;13(2):366-79.
- Iorga B, Schwanke K, Weber N, Wendland M, Greten S, Piep B, Dos Remedios CG, Martin U, Zweigerdt R, Kraft T, Brenner B. Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms. Frontiers in physiology. 2017;8:1111.
- Weber N, Schwanke K, Greten S, Wendland M, Iorga B, Fischer M, Geers-Knorr C, Hegermann J, Wrede C, Fiedler J, Kempf H, Franke A, Piep B, Pfanne A, Thum T, Martin U, Brenner B, Zweigerdt R, Kraft T. Stiff matrix induces switch to pure beta-cardiac myosin heavy chain expression in human ESC-derived cardiomyocytes. Basic research in cardiology. 2016;111(6):68.
Selected published abstructs
- Weber N., Holler T., Meißner J., Montag J., Peschel N., Mayer A., Schwanke K., Piep B., Martin U., Zweigerdt R., Kraft T. Pluripotent stem cell-derived cardiomyocytes from a patient with Arg723Gly β-myosin heavy chain mutation show alterations in twitch contractions, calcium transients and highly variable allele specific expression of mutant/wildtype β-MyHC mRNA. Circulation.2019;140:A13008. AHA Scientific Sessions Conference, Philadelphia, USA, 2019.
- Kowalski K., Weber N., Holler T., Radocaj A., Fischer M., de la Roche J., Tiemann S., Schwanke K., Piep B., Lingk A., Krumm U., Martin U., Zweigerdt R., Brenner B., Kraft T. Twitch kinetics and action potential parameters are independent of expressed myosin heavy chain isoform in human stem cell-derived cardiomyocytes. Acta physiologica, October 2019, Volume 227, Issue S719, pp146-147. Deutsche Physiologische Tagung 2019.
- Weber N., Holler T., Peschel N., Schwanke K., Piep B., Martin U., Zweigerdt R., Kraft T. Pluripotent stem cell-derived cardiomyocytes from a patient with Arg723Gly β-myosin heavy chain mutation as model for Hypertrophic Cardiomyopathy? J Muscle Res Cell Motil (2019) 40:272-273. European Muscle Conference, Canterbury, UK, 2019.
- Grunert M., Appelt S., Weber N., Huanhuan Cui, Fleur E. Mason, Niels Voigt, Silke R. Sperling. Induced pluripotent stem cell of patients with Tetralogy of Fallot reveal alterations in cardiomyocyte differentiation [version 1; not peer reviewed]. F100Research 2019, 8:1192 (poster) (doi:10.7490/f1000research.1117120.1). ISMB/ECCB, Basel, Switzerland, 2019.
- Weber N., Kowalski K., Holler T., Radocaj A., Fischer M., de la Roche J., Thiemann S., Schwanke K., Lingk A., Krumm U., Piep B, Martin U., Zweigerdt R., Brenner B., Kraft T. In human embryonic stem cell-derived cardiomyocytes twitch kinetics and action potential parameters are independent of the xpressed myosin heavy chain isoform. Biophysical Journal, Vol. 116, Issue 3, Suppl. 1, p118a. Biophysical Society Meeting, Baltimore, USA, 2019. Recipient of Travel Award from the Biophysical Society 2019.
- Weber N., Kowalski K., Holler T., Radocaj A., Schwanke K., Lingk A., Krumm U., Wendland M., Zywietz U., Chichkov B., Martin U., Zweigerdt R., Bernhard Brenner, Theresia Kraft. Human Embryonic Stem-Cell Derived Cardiomyocytes: Single-Cell Mapping to Relate Twitch Kinetics to Myosin Heavy Chain Protein and mRNA-Expression. Biophysical Journal 114 (3): 549a. Biophysical Society Meeting, San Fransisco, USA, 2018.
- Iorga B., Weber N., Schwanke K., Piep B., Wendland M., Greten S., Martin U., Zweigerdt R., Kraft T., Brenner B. Do β-Myosin heavy chain isoform-expressing myofibrils within human ESC-derived cardiomyocytes recapitulate the contractile features of adult human ventricular myofibrils?, J. Muscle Res. Cell. Motil., 2017, 38:391, DOI 10.1007/s10974-017-9490-8; European Muscle Conference, 2017, Potsdam, Germany
- Weber N., Kowalski K., Holler T., Lingk A., Radocaj A., Krumm U., Wendland M., Zywietz U., Chichkov B., Schwanke K., Martin U., Zweigerdt R., Brenner B., Kraft T. Single cell mapping used to assign mRNA and protein expression of cardiac myosin heavy chain to twitch kinetics of the same human embryonic stem cell derived cardiomyocyte. J Muscle Res Cell Motil 38:344. European Muscle Conference, Potsdam, GER, 2017. Young Investigator Award, 1st place.
- Weber N., Iorga B., Greten S., Wendland M., Schwanke K., Martin U., Brenner B., Zweigerdt R., Kraft T. Expression of fast vs. slow cardiac myosin heavy chain in human embryonic stem-cell derived cardiomyocytes: Effects on force generation, tension cost and time course of twitches. Acta physiologoca; vol. 213, Issue S699, page 113, P114. German Annual Physiology Society Conference, Magdeburg, 2015. Travel grant to the conference given by the German Physiology Society.
- Sarah Konze
Course instructor: practical courses for students of medicine, dentistry and biology, several topics of physiology.
Course instructor: seminars for students of medicine, several topics of physiology.
Supervision of Bachelor and Master theses for biochemistry / (molecular) biology students
- Dr. Joachim Meißner
Course instructor: practical courses for students of medicine, dental medicine and biology, several topics of physiology.
Course instructor: seminars for students of medicine, several topics of physiology.
- Felix Osten
Course instructor: practical courses for students of medicine, dental medicine and biology, topic muscle.
- Karina Ivaskevica
Course instructor: practical courses for students of medicine, dentistry and biology, several topics of physiology.