A5058096981- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- CRISPR and Genetic Engineering
- Ion channel regulation and function
- Pluripotent Stem Cells Research
- Epilepsy research and treatment
- 3D Printing in Biomedical Research
- RNA and protein synthesis mechanisms
University of California System
2021
University of California, Irvine
2017-2019
Over 1250 mutations in SCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes activity we generated two pairs isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is control line from an unaffected sibling, and mutated carrying GEFS+ K1270T SCN1A mutation. The second patient corrected line. By comparing electrophysiological properties inhibitory...
Advances in genome sequencing have identified over 1300 mutations the SCN1A sodium channel gene that result genetic epilepsies. However, it still remains unclear how most individual within seizures. A previous study has shown K1270T (KT) mutation, linked to epilepsy with febrile seizure plus (GEFS+) humans, causes heat-induced activity associated a temperature-dependent decrease GABAergic neuron excitability Drosophila knock-in model. To examine behavioral and cellular effects of this...
The use of human induced pluripotent stem cell (hiPSC)-derived neuronal cultures to study the mechanisms neurological disorders is often limited by low efficiency and high variability in differentiation functional neurons. Here we compare properties neurons prepared with two hiPSC protocols, both plated on astroglial feeder layers. Using a protocol an expandable intermediate stage, only small percentage cells morphology were excitable 21-23days culture. In contrast, direct strategy same line...
Abstract Over 1250 mutations in SCN1A , the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes activity we generated two pairs isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is control line from an unaffected sibling, and mutated carrying GEFS+ K1270T mutation. The second patient corrected line. By comparing electrophysiological properties inhibitory...
Abstract Advances in genome sequencing have identified over 1300 mutations the SCN1A sodium channel gene that result genetic epilepsies. However, how individual within produce seizures remains elusive for most mutations. Previous work from our lab has shown K1270T (KT) mutation, which is linked to GEFS+ (Genetic Epilepsy with Febrile Seizure plus) humans, causes reduced firing of GABAergic neurons a Drosophila knock-in model. To examine effect this mutation mammals, we introduced equivalent...