A5023966250- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Congenital heart defects research
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Genetic Associations and Epidemiology
- Cardiac electrophysiology and arrhythmias
- Epilepsy research and treatment
- Phosphodiesterase function and regulation
- Glycogen Storage Diseases and Myoclonus
- Glycosylation and Glycoproteins Research
- Sympathectomy and Hyperhidrosis Treatments
- Drug Transport and Resistance Mechanisms
- Axon Guidance and Neuronal Signaling
- Neonatal and fetal brain pathology
- Metalloenzymes and iron-sulfur proteins
- Advanced biosensing and bioanalysis techniques
- interferon and immune responses
- Sleep and Wakefulness Research
- Genetic Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
Stanford University
2019-2025
Lucile Packard Children's Hospital
2021-2025
Stanford Medicine
2025
Organogenesis (United States)
2022
Neurosciences Institute
2022
Institute of Neurological Sciences
2020
Columbia University Irving Medical Center
2011-2017
Columbia University
2011-2015
Abstract Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT and other neuropsychiatric conditions 1 . TS type (TS1) caused gain-of-function variant in the alternatively spliced developmentally enriched CACNA1C exon 8A, as opposed to its counterpart 8. We previously uncovered several phenotypes neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron...
Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for DNA (mtDNA) maintenance. Mutations nuclear gene, TK2, cause TK2 deficiency, which manifests predominantly children as myopathy with mtDNA depletion. Molecular bypass therapy products, deoxycytidine monophosphate (dCMP) and deoxythymidine (dTMP), prolongs life span of Tk2-deficient (Tk2-/- ) mice by 2- to 3-fold. Because we observed rapid catabolism deoxynucleoside monophosphates (dT)...
It is currently unknown how often and in which ways a genetic diagnosis given to patient with epilepsy associated clinical management outcomes. To evaluate diagnoses patients are This was retrospective cross-sectional study of referred for multigene panel testing between March 18, 2016, August 3, 2020, outcomes reported May November 2020. The setting included commercial laboratory multicenter practices. Patients epilepsy, regardless sociodemographic features, who received pathogenic/likely...
Somatosensory pathways convey crucial information about pain, touch, itch and body part movement from peripheral organs to the central nervous system1,2. Despite substantial needs understand how these assemble develop pain therapeutics, clinical translation remains challenging. This is probably related species-specific features lack of in vitro models polysynaptic pathway. Here we established a human ascending somatosensory assembloid (hASA), four-part generated pluripotent stem cells that...
Carefully designed animal models of genetic risk factors are likely to aid our understanding the pathogenesis schizophrenia. Here, we study a mouse strain with truncating lesion in endogenous Disc1 ortholog model effects schizophrenia-predisposing mutation and offer detailed account consequences that this has on development function hippocampal circuit. We uncover widespread cumulative cytoarchitectural alterations dentate gyrus during neonatal adult neurogenesis, which include errors axonal...
Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is characterized by brief (<2 minutes) seizures with abrupt onset and offset stereotyped focal or generalized events occurring predominantly (but not exclusively) from sleep. Clinically, SHE can be challenging to distinguish psychogenic nonepileptic sleep disorders. Up 30% of cases are drug-resistant, represents about 10% drug-resistant surgical cases. Although most have an unknown etiology, there a...
Abstract In human genetic studies of schizophrenia, we uncovered copy-number variants in RAPGEF6 and RAPGEF2 genes. To discern the effects deletion humans, investigated behavior neural functions a mouse lacking Rapgef6 . resulted impaired amygdala function measured as reduced fear conditioning anxiolysis. Hippocampal-dependent spatial memory prefrontal cortex-dependent working tasks were intact. Neural activation by cFOS phosphorylation demonstrated reduction hippocampal after conditioning,...
Abstract We report three unrelated probands, two male and one female, diagnosed with Aicardi‐Goutières syndrome (AGS) after screening positive on California newborn (CA NBS) for X‐linked adrenoleukodystrophy (X‐ALD) due to elevated C26:0 lysophosphatidylcholine (C26:0‐LPC). Follow‐up evaluation was notable C26:0, C26:1, C26:0/C22:0 ratio, normal red blood cell plasmalogens levels in all probands. Diagnoses were confirmed by molecular sequencing prior 12 months of age clinical inconsistent...
Abstract Background FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities. Objectives We describe 2 presenting childhood‐onset nystagmus, seizures carrying pathogenic de novo variants. Weighted gene co‐expression network analysis (WGCNA) was performed to gain insights into the function of brain. Methods Trio‐based whole‐exome sequencing both patients, CoExp web tool used conduct WGCNA . Results Both presented seizures. Previously...
Ferredoxin reductase (FDXR) is a flavoprotein that functions in both iron sulfur cluster biogenesis and steroid biosynthesis pathways the mitochondria. Not surprisingly, loss of FDXR function causes severe mitochondrial diseases humans. Although several FDXR-related mitochondriopathy (FRM) cohorts have been reported literature, further characterization natural history FRM warranted.
A previously healthy 15-year-old boy presented with 3 months of progressive psychosis, insomnia, back and groin pain, hyperhidrosis. On examination, the patient was disheveled, agitated, soaked sweat, systolic blood pressure in 160s heart rate 130s. Aside from occasional auditory visual hallucinations, his neurologic examination normal. The admitted for an extensive workup, including MRI brain spine lumbar puncture, which were Through collaboration various pediatric specialists, psychiatry...
Introduction Abulia is defined as a pathological state of amotivation, apathy, and global absence willpower. It presents with challenging array overlapping symptoms, making effective identification treatment difficult. Case Presentation We describe the first known report an adolescent ventricular assist device who developed abulia following left middle cerebral artery (MCA) stroke responded successfully to olanzapine. Discussion The neurobiological etiology still unclear but postulated be...