A5068770787- Neuroscience and Neuropharmacology Research
- CAR-T cell therapy research
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Ion channel regulation and function
- Viral Infectious Diseases and Gene Expression in Insects
- Ion Channels and Receptors
- Hearing, Cochlea, Tinnitus, Genetics
- RNA regulation and disease
- Memory and Neural Mechanisms
- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Chinese history and philosophy
- Cellular Mechanics and Interactions
- Cardiac Ischemia and Reperfusion
- Virus-based gene therapy research
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- Nanowire Synthesis and Applications
- Biosimilars and Bioanalytical Methods
- Biochemical Analysis and Sensing Techniques
- Phosphodiesterase function and regulation
- Nicotinic Acetylcholine Receptors Study
St. Jude Children's Research Hospital
2012-2023
Hubei University of Medicine
2012-2020
Wuhan University
2017
Zhongnan Hospital of Wuhan University
2017
House Clinic
2016
Michigan State University
2008-2015
Michigan United
2011
University of Maryland, Baltimore
2003-2004
The mechanism of receptor-induced activation the ubiquitously expressed family mammalian canonical transient receptor potential (TRPC) channels has been focus intense study. Primarily responding to phospholipase C (PLC)-coupled receptors, are reported receive modulatory input from diacylglycerol, endoplasmic reticulum inositol 1,4,5-trisphosphate receptors and Ca2+ stores. Analysis TRPC5 transfected within DT40 B cells deletion mutants thereof revealed efficient in response PLC-β or PLC-γ...
Activity-dependent transcription of brain-derived neurotrophic factor (BDNF) has been studied as an important model to elucidate the mechanisms underlying numerous aspects neuroplasticity. It extensively emphasized that Ca2+ influx through different routes may have significantly effects on BDNF transcription. Here, we examined regulatory property major calcium responsive elements (CaRE) in promoter IV cultured rat cortical neurons. IV, well CaRE1 and CaRE3, was activated by L-type...
In vivo direct conversion of differentiated cells holds promise for regenerative medicine; however, improving the efficiency and producing functional target remain challenging. Ectopic Atoh1 expression in non-sensory supporting (SCs) mouse cochleae induces their partial to hair (HCs) at low efficiency. Here, we performed single-cell RNA sequencing whole sensory epithelia harvested multiple time points after conditional overexpression Atoh1. Pseudotemporal ordering revealed that converted HCs...
Ca-stimulated adenylyl cyclases (ACs) transduce neuronal stimulation-evoked increase in calcium to the production of cAMP, which impinges on regulation many aspects function. Type 1 and type 8 AC (AC1 AC8) are only ACs that directly stimulated by Ca. Although AC1 function was implicated regulating reference spatial memory, AC8 memory formation is not known. Because different biochemical properties AC8, these two enzymes may have distinct functions. For example, activity regulated both Ca...
Abstract The induction of the immediate early gene Arc is strongly implicated in synaptic plasticity. Although role ERK has been demonstrated, regulation expression largely unknown. In this study, we investigated major signaling pathways underlying brain‐derived neurotrophic factor (BDNF)‐mediated transcription cultured cortical neurons. BDNF‐stimulated was regulated solely by Ras‐Raf‐MAPK through ERK, but not phosphoinositide 3‐kinase (PI3K) and PLC‐γ activities. it demonstrated that BDNF...
Abstract The general features of neuroplasticity are developmentally regulated. Although it has been hypothesized that the loss plasticity in mature neurons may be due to synaptic saturation and functional reduction N‐methyl‐D‐aspartate receptors (NMDAR), molecular mechanisms remain largely unknown. We examined effects NMDAR activation KCl‐mediated membrane depolarization on ERK1/2 signaling following vitro maturation cultured cortical neurons. NMDA stimulated a robust increase intracellular...
Acetylcholine (ACh) plays an important role in neural and non-neural function, but its mesenchymal stem cell (MSC) migration remains to be determined. In the present study, we have found that ACh induces MSC via muscarinic acetylcholine receptors (mAChRs). Among several mAChRs, MSCs express mAChR subtype 1 (m1AChR). interaction with mAChR1. MEK1/2 inhibitor PD98059 blocks ERK1/2 phosphorylation while partially inhibiting ACh-induced migration. InsP3Rs 2-APB inhibits MAPK/ERK completely...
Abstract The mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway plays an important role in brain‐derived neurotrophic factor (BDNF)‐mediated protein synthesis and neuroplasticity. Although many aspects neuronal function are regulated by intracellular calcium ([Ca 2+ ] i ) calmodulin (CaM), their functions BDNF‐induced phosphorylation p70S6K largely unknown. Here, we report that BDNF, via TrkB‐dependent activation mTOR, induces sustained at Thr389 Thr421/Ser424. was dependent on...
Autism spectrum disorders (ASDs) are a group of neurodevelopmental afflictions characterized by repetitive behaviors, deficits in social interaction, and impaired communication skills. For most ASD patients, the underlying causes unknown. Genetic mutations have been identified about 25 percent cases, including epigenetic regulators, suggesting that dysregulated chromatin or DNA function is critical component ASD. Mutations histone acetyltransferase CREB binding protein (CBP, CREBBP) cause...
Abstract Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS’ role in phenotype, sarcomere organization, energy metabolism of infarcted hearts. VNS vivo acetylcholine (ACh) vitro optimized levels α/β-MHC α-Actinin positive organization cardiomyocytes while reducing F-actin assembly cardiomyocytes. Consistently, ACh improved glucose uptake decreasing lipid deposition...
The mammalian cochlea is a highly specialized organ within the inner ear. Sensory hair cells (HC) in detect and transduce sound waves into electrical impulses that are sent to brain. Studies of molecular pathways regulating HC formation hindered by very sparse nature HCs, where only ~3300 found an entire mouse cochlea. Current cell lines mimic certain aspects HCs but lack terminal marker expression. Here we successfully "pseudo-immortalized" cochlear progenitor using "conditional...
Chimeric antigen receptor (CAR) T cells targeting CD123, an acute myeloid leukemia (AML) antigen, hold the promise of improving outcomes for patients with refractory/recurrent disease. We generated five lentiviral vectors encoding CD20, which may serve as a target CAR cell depletion, and 2nd or 3rd generation CD123-CARs since benefit two costimulatory domains is model dependent. Four CARs were based on CD123-specific single-chain variable fragment (scFv) 26292 (292) one scFv 26716 (716),...
TRPC channels are widely expressed among cells and believed to play important roles in receptor-mediated Ca2+ signalling. We determined that the function of is highly regulated by protein kinase C (PKC). Application diacylglycerol (DAG) or elevated endogenous DAG resulting from either DAG-lipase DAG-kinase inhibition, completely prevented TRPC5 TRPC4 activation both HEK293 DT40 cells. This inhibitory action on was clearly mediated PKC, distinction stimulatory TRPC3 which PKC-independent. PKC...
Abstract Brain‐derived neurotrophic factor (BDNF) mediates survival and neuroplasticity through the activation of phosphoinositide 3‐kinase‐Akt pathway. Although previous studies suggested roles mitogen‐activated protein kinase, phospholipase C‐γ‐mediated intracellular calcium ([Ca 2+ ] i ) increase, extracellular influx in regulating Akt activation, cellular mechanisms are largely unknown. We demonstrated that sub‐nanomolar BDNF significantly induced developing cortical neurons. The...
The N-methyl-D-aspartate (NMDA) receptor (NMDAR)-stimulated autophosphorylation of calmodulin-dependent kinase IIα at Thr286 may regulate many aspects neuroplasticity. Here, we show that low NMDA concentration (20 μM) up-regulated phosphorylation, and high (100 caused dephosphorylation. We next modulated the strength NMDAR activation by manipulating 2A subunit (NR2A) 2B (NR2B), which represent major subtypes in forebrain regions. Pharmacological inhibition molecular knockdown NR2A or NR2B...
The mechanisms by which Ca2+-store-release channels and Ca2+-entry are coupled to receptor activation poorly understood. Modification of Ca2+ signals 2-aminoethoxydiphenyl borate (2-APB), suggests the agent may target entry or machinery controlling their activation. In DT40 B-cells Jurkat T-cells, complete store release was induced 2-APB (EC50 10–20 µM). At 75 µM, emptied stores completely in both lymphocyte lines, but had no such effect on other cells. cells, mimicked B-cell (BCR)...
The activity of Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is sensitive to activity-dependent changes in the level intracellular Ca(2+). Following neuronal stimulation, activation CaMKIV may trigger synaptic modifications and transcriptional responses, both which are involved regulating cognitive emotional behavior. Here, we used knockout (KO) neurons mice examine function Ca(2+)-stimulated signaling animal behavior, respectively. NMDA receptor or membrane depolarization,...