Patient-specific induced pluripotent stem cell models to elucidate the role of TRPM4 channels in the pathogenesis of inherited cardiac arrhythmia (P17)

• Subject Area: Anatomy and Physiology
• Term: since 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 239283807

TRPM4 channels are Ca2+ activated, non-selective cation channels that participate in a plethora of cardiac functions including the myocyte`s electrical excitability. Dominantly inherited mutations in the TRPM4 gene are associated with several forms of cardiac arrhythmias and conduction diseases. We identified TRPM4’s Ca2+-dependent gating behavior as a novel contributor to the aberrant membrane current and introduced that as the causal mechanism of TRPM4 mutation dependent human arrhythmia. Taking advantage of CRISPR/Cas9-mediated TRPM4 knock-out hiPSC lines, hiPSC-derived 3D cardiac organoids and engineered heart patches , this project aims at investigating how exactly TRPM4 mutations contribute to malfunction of the heart and whether functional characteristics of TRPM4 mutants correlate with a specific clinical phenotype.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 152: TRiPs to Homeostasis: Maintenance of Body Homeostasis by Transient Receptor Potential Channel Modules
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Heads: Professor Dr. Karl-Ludwig Laugwitz; Professor Dr. Peter Lipp, Ph.D.; Professorin Dr. Alessandra Moretti, Ph.D.