A5088678361- Ion channel regulation and function
- Ion Channels and Receptors
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Neurobiology and Insect Physiology Research
- Neuroscience and Neural Engineering
- Genomics and Rare Diseases
- Nicotinic Acetylcholine Receptors Study
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Electrochemical Analysis and Applications
- Genetic Neurodegenerative Diseases
- Insect and Pesticide Research
- Biochemical Analysis and Sensing Techniques
- Nuclear Physics and Applications
- Insect and Arachnid Ecology and Behavior
- CRISPR and Genetic Engineering
- Microfluidic and Capillary Electrophoresis Applications
- Pluripotent Stem Cells Research
- Connexins and lens biology
- Mass Spectrometry Techniques and Applications
- Neurotransmitter Receptor Influence on Behavior
- Aquaculture Nutrition and Growth
- Membrane-based Ion Separation Techniques
Broad Institute
2018-2024
Massachusetts Institute of Technology
2020
University of Valparaíso
2010-2018
Valparaiso University
2014-2015
Centro Científico Tecnológico de Valparaíso
2014
Buffalo State University
2012
University at Buffalo, State University of New York
2012
Malfunctions of voltage-gated sodium and calcium channels (encoded by
Abstract Objective Voltage‐gated sodium channels (SCNs) share similar amino acid sequence, structure, and function. Genetic variants in the four human brain‐expressed SCN genes SCN1A/2A/3A/8A have been associated with heterogeneous epilepsy phenotypes neurodevelopmental disorders. To better understand biology of seizure susceptibility ‐related epilepsies, our aim was to determine similarities differences between channel disorders, allowing us develop a broader perspective on precision...
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been recognized as an important activator of certain transient receptor potential (TRP) channels. More specifically, TRPV1 is a pain activated by wide range stimuli. However, whether or not PI(4,5)P2 agonist remains open to debate. Utilizing combined approach mutagenesis and molecular modeling, we identified binding site located between the TRP box S4-S5 linker. At this site, interacts with amino acid residues Arg-575 Arg-579 in linker...
Abstract Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A , encoding for the GluN2A subunit of NMDA receptors, that confer significant risk schizophrenia (SCZ). Mutations are also associated with epilepsy developmental delay/intellectual disability (DD/ID). However, it remains enigmatic how alterations to same protein can result diverse clinical phenotypes. Here, we performed functional characterization human GluN1/GluN2A heteromeric receptors...
Glioblastoma is a lethal brain cancer that commonly recurs after tumor resection and chemotherapy treatment. Depolarized resting membrane potentials an acidic intertumoral extracellular pH have been associated with proliferative state drug resistance, suggesting forced hyperpolarization disruption of proton pumps in the plasma could be successful strategy for targeting glioblastoma overgrowth. We screened 47 compounds compound combinations, most which were ion-modulating, at different...
Overexpression of mouse neurogenin (Neurog)2 alone or in combination with Neurog2/1 human embryonic stem cells (hESCs) and induced pluripotent (hiPSCs) can rapidly produce high-yield excitatory neurons. Here, we report a detailed characterization neuronal networks by the expression NEUROG2 together NEUROG2/1 hESCs using molecular, cellular, electrophysiological measurements over 60 d after induction. Both synaptic transmission network firing activity increased time. Strikingly, inhibitory...
Abstract CACNA1I , a schizophrenia risk gene, encodes subtype of voltage-gated T-type calcium channel Ca V 3.3. We previously reported that patient-derived missense de novo mutation (R1346H) impaired 3.3 function. Here, we generated 3.3-RH knock-in animals, along with mice lacking 3.3, to investigate the biological impact R1346H (RH) variation. found RH altered cellular excitability in thalamic reticular nucleus (TRN), where is abundantly expressed. Moreover, produced marked deficits sleep...
CACNA1A encodes the P/Q-type CaV2.1 calcium channels whose function underlies neuronal excitability, presynaptic neurotransmitter release, and Ca 2+ signaling in neurons. Pathogenic variants have been found individuals with various neurological conditions, including hemiplegic migraine, epilepsy, developmental delay, ataxia. Clinical presentations can vary significantly between patients, limited information known about underlying neurobiology of these different clinical patterns. Adding...
As ectotherms, insects need heat-sensitive receptors to monitor environmental temperatures and facilitate thermoregulation. We show that
Mammalian transient receptor potential (TRP) channels consist of at least seven families related proteins. A subset belong to the TRP channel superfamily, and they are responsible for temperature detection in mammals. These (thermoTRPs) expressed primarily dorsal root
T-type voltage-gated Ca
Summary Malfunctions of voltage-gated sodium and calcium channels (SCN CACNA1 genes) have been associated with severe neurologic, psychiatric, cardiac other diseases. Altered channel activity is frequently grouped into gain or loss ion function (GOF LOF, respectively) which not only corresponding to clinical disease manifestations, but also differences in drug response. Experimental studies are therefore important, laborious usually focus on a few variants at time. Based known...
Abstract Potassium channels are particularly important in determining the shape and duration of action potential, controlling membrane modulating hormone secretion, epithelial function and, case those K + activated by Ca 2+ , damping excitatory signals. The multiplicity roles played is only possible to their mammoth diversity that includes at present 70 encoding genes mammals. Today, thanks use cloning, mutagenesis, more recent structural studies using x‐ray crystallography, we a unique...
Abstract Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A , encoding for the GluN2A subunit of NMDA receptors, that confer significant risk schizophrenia (SCZ). Mutations are also associated with epilepsy developmental delay/intellectual disability (DD/ID). However, it remains enigmatic how alterations to same protein can result diverse clinical phenotypes. Here, we performed functional characterization human GluN1/GluN2A heteromeric receptors...
Abstract Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A, encoding for the GluN2A subunit of NMDA receptors, that confer significant risk schizophrenia (SCZ). Mutations GRIN2A are also associated with epilepsy developmental delay/intellectual disability (DD/ID). However, it remains enigmatic how alterations to same protein can result diverse clinical phenotypes. Here, we performed functional characterization human receptors (GluN1/GluN2A...