Lukas Cyganek
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View article: Phenotypes in Brugada syndrome with different genotypes triggered by fever or inflammation using gene-edited iPSCs
Phenotypes in Brugada syndrome with different genotypes triggered by fever or inflammation using gene-edited iPSCs Open
Background Fever or inflammation state may enhance the Brugada syndrome (BrS) phenotype in some but not all patients. However, the underlying mechanism in human cardiomyocytes has not yet been clarified. Methods Human induced pluripotent s…
View article: Peroxisome protein import deficiency causes heart failure in mouse and human
Peroxisome protein import deficiency causes heart failure in mouse and human Open
Peroxisomes are ubiquitous cellular organelles with potentially vital roles in lipid and reactive oxygen metabolism. The metabolic demands of the heart are substantial; however, the contribution of peroxisomes to cardiac development, healt…
View article: Variant U1 snRNAs contribute to cell cycle and differentiation control of human iPS cells
Variant U1 snRNAs contribute to cell cycle and differentiation control of human iPS cells Open
Maintenance of stem cell identity as well as differentiation of stem cells into the various lineages requires intricate regulation of gene expression. Despite intensive research, our understanding of these regulatory networks remains incom…
View article: Efficient and sustained optogenetic control of sensory and cardiac systems
Efficient and sustained optogenetic control of sensory and cardiac systems Open
Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal …
View article: Pluripotent stem cell-based drug discovery uncovers sildenafil as a treatment for mitochondrial disease
Pluripotent stem cell-based drug discovery uncovers sildenafil as a treatment for mitochondrial disease Open
Mitochondrial disease encompasses inherited disorders affecting mitochondrial function. A severe and untreatable form of mitochondrial disease is Leigh syndrome (LS) causing psychomotor regression and metabolic crises. To accelerate drug d…
View article: SarcAsM: AI-based multiscale analysis of sarcomere organization and contractility in cardiomyocytes
SarcAsM: AI-based multiscale analysis of sarcomere organization and contractility in cardiomyocytes Open
Cardiomyocyte function critically depends on sarcomere dynamics and their organization in myofibrils. To uncover how cardiomyocyte function emerges from individual sarcomere dynamics, comprehensive analysis of Z-bands (nanometer scale), sa…
View article: BTRR complex deficiency is a driver for genomic instability in Bloom syndrome
BTRR complex deficiency is a driver for genomic instability in Bloom syndrome Open
Biallelic loss-of-function (LoF) variants in the BTRR complex members BLM , TOP3A, RMI1, and RMI2 cause Bloom syndrome (BS). The BTRR complex mainly acts on DNA replication and DNA repair processes, and dysfunction of this complex underlie…
View article: SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis
SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis Open
As a major component of intracellular trafficking, the coat protein complex II (COPII) is indispensable for cellular function during embryonic development and throughout life. The 4 SEC24 proteins (A-D) are essential COPII components invol…
View article: Exosomal mir-126-3p derived from endothelial cells induces ion channel dysfunction by targeting RGS3 signaling in cardiomyocytes: a novel mechanism in Takotsubo cardiomyopathy
Exosomal mir-126-3p derived from endothelial cells induces ion channel dysfunction by targeting RGS3 signaling in cardiomyocytes: a novel mechanism in Takotsubo cardiomyopathy Open
View article: Esophageal Cancer-Related Gene-4 Contributes to Lipopolysaccharide-Induced Ion Channel Dysfunction in hiPSC-Derived Cardiomyocytes
Esophageal Cancer-Related Gene-4 Contributes to Lipopolysaccharide-Induced Ion Channel Dysfunction in hiPSC-Derived Cardiomyocytes Open
This study demonstrated that LPS effects on cardiac ion channel function were mediated by the upregulation of ECRG4, which affects NFκB signaling. Our findings support the roles of ECRG4 in inflammatory responses and the ion channel dysfun…
View article: CardioMEA: comprehensive data analysis platform for studying cardiac diseases and drug responses
CardioMEA: comprehensive data analysis platform for studying cardiac diseases and drug responses Open
Introduction In recent years, high-density microelectrode arrays (HD-MEAs) have emerged as a valuable tool in preclinical research for characterizing the electrophysiology of human induced pluripotent stem-cell-derived cardiomyocytes (iPSC…
View article: Generation of a heterozygous Calsequestrin 2 F189L iPSC line (UMGi158-B) by CRISPR/Cas9 genome editing to investigate the cardiac pathophysiology of Takotsubo Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia
Generation of a heterozygous Calsequestrin 2 F189L iPSC line (UMGi158-B) by CRISPR/Cas9 genome editing to investigate the cardiac pathophysiology of Takotsubo Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia Open
Takotsubo Syndrome (TTS) is a potentially life-threatening disease characterized by a transient left ventricular apical akinesia in response to β-adrenergic overstimulation. Since a genetic predisposition is assumed, we generated an iPSC-l…
View article: Mutation-induced LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome
Mutation-induced LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome Open
Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. In this study, we investigate the mechanistic consequences of a homozygous variant LZTR1…
View article: mtDNA analysis using Mitopore
mtDNA analysis using Mitopore Open
Mitochondrial DNA (mtDNA) analysis is crucial for the diagnosis of mitochondrial disorders, forensic investigations, and basic research. Existing pipelines are complex, expensive, and require specialized personnel. In many cases, including…
View article: Preclinical evaluation of CRISPR-based therapies for Noonan syndrome caused by deep-intronic LZTR1 variants
Preclinical evaluation of CRISPR-based therapies for Noonan syndrome caused by deep-intronic LZTR1 variants Open
Gene variants in LZTR1 are implicated to cause Noonan syndrome associated with a severe and early-onset hypertrophic cardiomyopathy. Mechanistically, LZTR1 deficiency results in accumulation of RAS GTPases and, as a consequen…
View article: Noninvasive analysis of contractility during identical maturations revealed two phenotypes in ventricular but not in atrial iPSC-CM
Noninvasive analysis of contractility during identical maturations revealed two phenotypes in ventricular but not in atrial iPSC-CM Open
Differentiation of induced pluripotent stem cells (iPSCs) into iPSC-derived cardiomyocytes (iPSC-CMs) exhibits a high variability in mature parameters. Here, we monitored noninvasively contractile parameters of iPSC-CM during full-time dif…
View article: Efficient and sustained optogenetic control of sensory and cardiac systems
Efficient and sustained optogenetic control of sensory and cardiac systems Open
Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal …
View article: Flagellin-Induced Immune Response in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Flagellin-Induced Immune Response in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Open
Pathogen-associated molecular patterns (PAMPs) are involved in the pathogenesis of septic cardiomyopathy through a toll-like receptor (TLR)-mediated immune response. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) ca…
View article: Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development
Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development Open
Aims Atrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies is hampered by the absence …
View article: Metabolic switch from fatty acid oxidation to glycolysis in knock‐in mouse model of Barth syndrome
Metabolic switch from fatty acid oxidation to glycolysis in knock‐in mouse model of Barth syndrome Open
View article: Combining a tetracycline (Tet)-inducible gRNA system and CRISPRa for titratable and timely controlled enhancement of endogenous SHISA3 activation in human induced pluripotent stem cells (hiPSC)
Combining a tetracycline (Tet)-inducible gRNA system and CRISPRa for titratable and timely controlled enhancement of endogenous SHISA3 activation in human induced pluripotent stem cells (hiPSC) Open
Towards increasing the possibility for temporal control of gene expression using CRISPR activation (a) systems, we generated homozygous human induced pluripotent stem cell (hiPSC) lines carrying a doxycycline (dox)-inducible guide(g)-RNA c…
View article: Molecular and cellular evidence for the impact of a hypertrophic cardiomyopathy-associated RAF1 variant on the structure and function of contractile machinery in bioartificial cardiac tissues
Molecular and cellular evidence for the impact of a hypertrophic cardiomyopathy-associated RAF1 variant on the structure and function of contractile machinery in bioartificial cardiac tissues Open
Noonan syndrome (NS), the most common among RASopathies, is caused by germline variants in genes encoding components of the RAS-MAPK pathway. Distinct variants, including the recurrent Ser257Leu substitution in RAF1, are associated with se…
View article: Generation of a genetically-modified induced pluripotent stem cell line harboring a Noonan syndrome-associated gene variant MRAS p.G23V
Generation of a genetically-modified induced pluripotent stem cell line harboring a Noonan syndrome-associated gene variant MRAS p.G23V Open
Patients harboring causative gene variants in RAS GTPase MRAS develop Noonan syndrome and early-onset hypertrophic cardiomyopathy. Here, we describe the generation of a human iPSC line harboring the Noonan syndrome-associated MRAS p.G23V v…
View article: Generation of a genetically-modified induced pluripotent stem cell line harboring an oncogenic gene variant KRAS p.G12V
Generation of a genetically-modified induced pluripotent stem cell line harboring an oncogenic gene variant KRAS p.G12V Open
Activating KRAS codon 12 gene variants are known to cause severe RAS-MAPK and PI3K-AKT signaling pathway hyperactivity and are frequently involved in the development of various carcinomas. Here, we describe the generation of a human iPSC l…
View article: Electrophysiological and calcium-handling development during long-term culture of human-induced pluripotent stem cell-derived cardiomyocytes
Electrophysiological and calcium-handling development during long-term culture of human-induced pluripotent stem cell-derived cardiomyocytes Open
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used for personalised medicine and preclinical cardiotoxicity testing. Reports on hiPSC-CM commonly describe heterogenous functional readouts and under…
View article: Novel insights in the pathomechanism of Brugada syndrome and fever‐related type 1 ECG changes in a preclinical study using human‐induced pluripotent stem cell‐derived cardiomyocytes
Novel insights in the pathomechanism of Brugada syndrome and fever‐related type 1 ECG changes in a preclinical study using human‐induced pluripotent stem cell‐derived cardiomyocytes Open
Background Brugada syndrome (BrS) is causing sudden cardiac death (SCD) mainly at young age. Studying the underlying mechanisms associated with BrS type I electrocardiogram (ECG) changes in the presence of fever and roles of autophagy for …
View article: LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome
LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome Open
Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. However, the underling disease mechanisms of LZTR1 missense variants driving the cardiac…
View article: Novel Insights in the Pathogenic Role of Fever and Inflammation in Brugada Syndrome - Study Using Gene-Edited Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Novel Insights in the Pathogenic Role of Fever and Inflammation in Brugada Syndrome - Study Using Gene-Edited Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Open
View article: Secreted-Frizzled-Related Protein 5 Modulates Calcium Handling in Human Ipsc-Cardiomyocytes
Secreted-Frizzled-Related Protein 5 Modulates Calcium Handling in Human Ipsc-Cardiomyocytes Open
View article: A modern automated patch-clamp approach for high throughput electrophysiology recordings in native cardiomyocytes
A modern automated patch-clamp approach for high throughput electrophysiology recordings in native cardiomyocytes Open