A5065984428- Epilepsy research and treatment
- CRISPR and Genetic Engineering
- Zebrafish Biomedical Research Applications
- Advanced biosensing and bioanalysis techniques
- RNA regulation and disease
- Virus-based gene therapy research
- Neuroscience and Neuropharmacology Research
- Advanced Data Storage Technologies
- Innovative Microfluidic and Catalytic Techniques Innovation
- Ion channel regulation and function
- Cardiovascular Effects of Exercise
- Neonatal and fetal brain pathology
- Autism Spectrum Disorder Research
- Genomics and Rare Diseases
- MicroRNA in disease regulation
- Machine Learning in Bioinformatics
- Congenital heart defects research
- Electrochemical Analysis and Applications
- Cardiomyopathy and Myosin Studies
- Medical Imaging Techniques and Applications
- Parallel Computing and Optimization Techniques
- Molecular Biology Techniques and Applications
- Magnetic properties of thin films
University Medical Center Utrecht
2019-2023
Utrecht University
2019-2021
AtlantiCare
2021
ERN EpiCARE
2021
Dravet syndrome is caused by dominant loss-of-function mutations in SCN1A which cause reduced activity of Nav1.1 leading to lack neuronal inhibition. On the other hand, gain-of-function SCN8A can lead a severe epileptic encephalopathy subtype over activating NaV1.6 channels. These observations suggest that and Nav1.6 represent two opposing sides balance between inhibition activation. Here, we hypothesize may be treated either enhancing or reducing activity. To test this hypothesis generated...
Abstract The heterozygous Phospholamban p.Arg14del mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. This triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca 2+ dynamics. Little known about the physiological processes preceding induced cardiomyopathy, which characterized sub-epicardial accumulation of fibrofatty tissue, a specific drug treatment currently lacking. Here, we address these issues using knock-in zebrafish model....
Abstract Background Prime editing (PE) is the most recent gene technology able to introduce targeted alterations genome, including single base pair changes, small insertions, and deletions. Several improvements PE machinery have been made in past few years, these tested a range of model systems immortalized cell lines, stem cells, animal models. While double nicking RNA (dncRNA) PE3 PE5 currently show highest rates, they come with reduced accuracy as undesired indels or SNVs arise at edited...
Abstract Background Pathogenic variants in SCN1A cause variable epilepsy disorders with different disease severities. We here investigate whether common variation the promoter region of unaffected allele could reduce normal expression, leading to a decreased residual function Nav1.1, and therefore more severe clinical outcomes patients affected by pathogenic variants. Methods Five promoter‐haplotypes were functionally assessed SH‐SY5Y cells using Firefly Renilla luciferase assays. The was...
There are currently seven different zebrafish strains that model Dravet Syndrome, a severe childhood form of epilepsy. These models based on set duplicated genes, scn1laa and scn1lab, which the homologs for human SCN1A. Disrupting one genes would mimic heterozygous disease state in humans, as paralog gene is still present. While this 'disease-state model' widely accepted, there also evidence function these might not be completely same. By analyzing functional domains, we discovered several...
Dravet syndrome (DS) is a monogenic epileptic encephalopathy caused by loss-of-function mutations in the voltage-gated sodium channel (VGSC) gene SCN1A. DS has an age of onset within first year life and severe disease prognosis. In past years, it been shown that upregulation endogenous SCN1A can be beneficial animal models for DS, but complete rescue was not observed. We hypothesized during early development precedes symptoms might improve outcome. To test this hypothesis, we evaluated...
Abstract Dravet syndrome is caused by dominant loss-of-function mutations in SCN1A which cause reduced activity of Nav1.1 leading to lack neuronal inhibition. On the other hand, gain-of-function SCN8A can lead a severe epileptic encephalopathy subtype over activating Na V 1.6 channels. These observations suggest that and Nav1.6 represent two opposing sides balance between inhibition activation. Here, we hypothesize may be treated either enhancing or reducing activity. To test this hypothesis...
ABSTRACT Prime editing (PE) is currently the most effective and versatile technology to make targeted alterations in genome. Several improvements PE machinery have recently been made, tested a range of model systems, including immortalized cell lines, stem-cells animal models. While nick RNA (ncRNA)-dependent systems like PE3 PE5 are considered be effective, they come with undesired indels or SNVs at edit locus. Here, we aimed improve ncRNA-independent PE2 PE4max by generating novel...