Pluripotent stem cell (PSC) derived cardiomyocytes (CM) offer unique possibilities, including the transplantation after myocardial infarction to regenerate the heart . However, limitations exist, including low cell retention and graft-induced arrhythmia. In this project, we want to tackle these issues by modulating cardiomyocyte functions in a transient manner using mRNA and nanoparticle technologies in vitro and in vivo.
PhD project description
This project aims to improve therapeutic perspectives of heart repair and involves generation and manipulation of primary and PSC-CMs. We will characterize their functions in vitro and in vivo with cutting-edge physiological and molecular technologies ranging from magnetic resonance and live-cell imaging to advanced sequencing technologies.
Required profile of the candidate
The ideal candidate will have strengths in the areas of stem cell and developmental biology, epigenetics, cardiovascular biology and regeneration. Bioinformatics skills are a plus.
Applicants should bring a structured, precise, and independent working attitude, an analytical way of thinking and outstanding problem-solving skills.
Excellent written and oral skills in English are expected.
We are searching for enthusiastic team players with a can-do attitude, innovative potential and a strong motivation to make a difference in biomedicine.
Publications relevant to the project
Weinberger, F. & Eschenhagen, T. Cardiac Regeneration: New Hope for an Old Dream. Annual Review of Physiology 83, 59-81 (2021). doi: 10.1146/annurev-physiol-031120-103629.
Stüdemann, T. et al. Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury. Circulation 146, 1159-1169 (2022).
Romagnuolo, R. et al. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias. Stem Cell Reports 12, 967-981 (2019). doi: 10.1016/j.stemcr.2019.04.005.
Marchiano, S. et al. Gene editing to prevent ventricular arrhythmias associated with cardiomyocyte cell therapy. Cell Stem Cell 30, 396-414.e399 (2023). doi: 10.1016/j.stem.2023.03.010.
Chen, Y. et al. Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice. Science 373, 1537-1540 (2021). doi: 10.1126/science.abg5159.