A5014906410- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Ion channel regulation and function
- Aluminum toxicity and tolerance in plants and animals
- Endoplasmic Reticulum Stress and Disease
- Glioma Diagnosis and Treatment
- Plant Stress Responses and Tolerance
- Autism Spectrum Disorder Research
- Epigenetics and DNA Methylation
- Intracerebral and Subarachnoid Hemorrhage Research
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Photoreceptor and optogenetics research
- Protein Tyrosine Phosphatases
- Cellular Mechanics and Interactions
- Estrogen and related hormone effects
- MicroRNA in disease regulation
- Neuroscience and Neural Engineering
- Cell Image Analysis Techniques
- Myasthenia Gravis and Thymoma
- thermodynamics and calorimetric analyses
Boston Children's Hospital
2022-2025
Harvard University
2024-2025
Changsha University of Science and Technology
2025
Boston Children's Museum
2024
Whitehead Institute for Biomedical Research
2016-2023
Sichuan University
2022
Pennsylvania State University
2010-2022
Harbin Medical University
2021
University of Helsinki
2021
University of California, San Diego
2015-2020
Significance Rett syndrome is a devastating neurodevelopmental disorder that currently has no cure. In this work, we demonstrate human neurons derived from patients with show significant deficit in neuron-specific K + -Cl − cotransporter2 (KCC2) expression, resulting delayed GABA functional switch. Restoring KCC2 level rescues deficits neurons. We further methyl CpG binding protein 2 regulates expression through inhibiting RE1-silencing transcriptional factor. Our data suggest potential...
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by loss-of-function heterozygous mutations of methyl CpG-binding protein 2 ( MECP2 ) on the X chromosome in young females. Reactivation silent wild-type allele from inactive (Xi) represents a promising therapeutic opportunity for female patients with RTT. Here, we applied multiplex epigenome editing approach to reactivate Xi RTT human embryonic stem cells (hESCs) and derived neurons. Demethylation promoter dCas9-Tet1...
Significance Understanding neurophysiological correlates of neurodevelopmental disorders is one the pressing challenges neuroscience. By analyzing a mouse model Rett syndrome (RTT), we show that cortical pyramidal neurons in methyl-CpG binding protein 2 (MeCP2) mutant mice have reduced excitatory as well inhibitory synaptic drive. Thus, neuronal response reliability and selectivity, features arise from excitatory/inhibitory processing circuits within cortex, are reduced. MeCP2 deletion...
KCC2 expression–enhancing small molecules rescue cellular and behavior deficits in human RTT neurons Mecp2 mutant mice.
Protein kinase R (PKR)-like endoplasmic reticulum (PERK) (EIF2AK3) is essential for normal development and function of the insulin-secreting β-cell. Although genetic ablation PERK in β-cells results permanent neonatal diabetes humans mice, underlying mechanisms remain unclear. Here, we used a newly developed highly specific inhibitor to determine immediate effects acute activity. We found that inhibition human rodent causes rapid secretagogue-stimulated subcellular Ca(2+) signaling insulin...
Precisely localizing the spatial distribution of proteins within various brain cell types and subcellular compartments, such as synapses, is essential for generating testing hypotheses to elucidate their roles in function. While fms-like tyrosine kinase-3 (Flt3) has been extensively studied context blood development leukemia pathogenesis, its role remains poorly understood. Previous efforts address this issue were hindered by low expression levels Flt3 limited sensitivity standard...
Abstract Mouse α4β2 nicotinic acetylcholine receptors (nAchRs) were stably expressed in HEK293T cells. The function of this stable cell line, termed mmα4β2, was assessed using an aequorin‐based luminescence method that measures agonist‐evoked changes intracellular calcium. Agonist‐elicited calcium due primarily to direct entry through the channel, although release from stores contributed ˜ 28% response. Agonist pharmacologies very similar between mmα4β2 cells and most lines express human...
Members of the Cys-loop superfamily ligand-gated ion channels, which mediate fast synaptic transmission in nervous system, are assembled as heteropentamers from a large repertoire neuronal subunits. Although several motifs subunit N-terminal domains known to be important for assembly, increasing evidence points toward role C-terminal domains. Using combination flow cytometry, patch clamp recording, endoglycosidase H digestion, brefeldin A treatment, and analytic centrifugation, we identified...
Protein kinase A (PKA) has been reported to regulate synaptic αβγ γ-aminobutyric acid type (GABA ) receptor currents, but whether PKA regulates GABA peri- and extrasynaptic tonic currents is unknown. receptors containing α4 subunits are important in mediating inhibition exist as both α4βδ α4βγ the brain. To mimic GABA-independent GABA-dependent we transfected HEK 293T cells with α4β3δ or α4β3γ2L recorded spontaneous absence of applied steady-state presence 1 μM GABA. Both displayed...
GABAA receptors (GABAA-Rs) play critical roles in brain development and synchronization of neural network activity. While synaptic GABAA-Rs can exert rapid inhibition, the extrasynaptic tonically inhibit neuronal activity due to constant activation by ambient GABA. The δ subunit-containing are expressed abundantly cerebellum, hippocampus thalamus mediate major tonic inhibition brain. electrophysiological pharmacological properties δ-GABAA-Rs have been well characterized, molecular...
The mechanism of estrogen deficiency-induced cognitive impairment is still not fully elucidated. In this study, we assessed the effect microRNA (miRNA) on memory long-term estrogen-deficient mice after ovariectomy (OVX) and normal aging. We observed that 5-month OVX 22-month-old aging female showed significantly impaired spatial object recognition memory, declined hippocampal potentiation (LTP), decreased protein kinase C α (PKCα) protein. Quantitative real-time PCR analysis upregulated...
PERK (EIF2AK3) is an ER-resident eIF2α kinase required for behavioral flexibility and metabotropic glutamate receptor-dependent long-term depression via its translational control. Motivated by the recent discoveries that regulates Ca2+ dynamics in insulin-secreting β-cells underlying glucose-stimulated insulin secretion, modulates signals-dependent working memory, we explored role of regulating Gq protein-coupled pyramidal neurons. We found acute inhibition use a highly specific inhibitor...
Protein quality control (PQC) targets misfolded proteins for degradation. Ubr1 is a key E3 ligase in PQC; it requires HSP70 this function. We show direct involvement of the ATP cycle PQC, suggesting model protein triage involving kinetic "race" between HSP-mediated folding and Ubr1-dependent ubiquitination.
Various approaches exist to assess population differences in biological aging. Telomere length (TL) is one such measure, and associated with disease, disability early mortality. Yet, issues surrounding precision reproducibility are a concern for TL measurement. An alternative method estimate using DNA methylation (DNAmTL) was recently developed. Although DNAmTL has been characterized adult elderly cohorts, its utility pediatric populations remains unknown. We examined the comparability of...
Although lots of new drugs are developed to treat Alzheimer’s disease (AD), many clinical trials monotherapy have failed affect progression or symptoms compared with placebo. Recently, scientists believe that combination treatment is more promising than monotherapy. Previous studies found microRNA-195 ( miR-195 ) was down-regulated in the hippocampi and cortices chronic brain hypoperfusion (CBH) rats ApoE4 (+/+) mice, up-regulation can improve declined cognitive function mice CBH by...
Although social-emotional skills are more malleable than cognitive and have potential benefits for a range of academic life outcomes, previous studies on the topic suffered from many issues (e.g., consideration only small subset skills, single-informant single-cohort design). To address these limitations, this study used multi-informant (self, teacher, parent) multi-cohort (ages 10 15 Finland, N = 5,533) perspective to association between 20 educational school grades), social relationships...
Protein kinase C (PKC) isozymes play essential roles in biological processes, and activation of PKC is proposed to alleviate the symptoms a variety diseases. It would be great significance find effective pharmacological modulators that can translated for clinical use. Here, using vitro activity assay, we demonstrated green tea extract (-)-epigallocatechin-3-gallate (EGCG) dose-dependently activated PKCα with half concentration (EC50) 0.49 μM. We also performed surface plasmon resonance...