Jian Xu, PhD
Research Scientist in PsychiatryCards
About
Research
Publications
2022
Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain
Dedek A, Xu J, Lorenzo LÉ, Godin AG, Kandegedara CM, Glavina G, Landrigan JA, Lombroso PJ, De Koninck Y, Tsai EC, Hildebrand ME. Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain. Brain 2022, 145: 1124-1138. PMID: 35323848, PMCID: PMC9050559, DOI: 10.1093/brain/awab408.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorSuperficial dorsal horn neuronsDorsal horn neuronsFemale ratsNeurotrophic factorNeuronal mechanismsCentral neuronal mechanismsSpinal nociceptive circuitsSpinal pain processingSuperficial dorsal hornChronic pain syndromeLamina I neuronsPreclinical pain modelsHuman organ donorsSynaptic NMDAR responsesNMDAR potentiationSpinal hyperexcitabilityInflammatory painNociceptive circuitsPain syndromeTactile allodyniaDorsal hornPain modelPathological painLaminae I
2020
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron typesInhibition of striatal-enriched protein tyrosine phosphatase (STEP) activity reverses behavioral deficits in a rodent model of autism
Chatterjee M, Singh P, Xu J, Lombroso PJ, Kurup PK. Inhibition of striatal-enriched protein tyrosine phosphatase (STEP) activity reverses behavioral deficits in a rodent model of autism. Behavioural Brain Research 2020, 391: 112713. PMID: 32461127, PMCID: PMC7346720, DOI: 10.1016/j.bbr.2020.112713.Peer-Reviewed Original ResearchAnimalsAutism Spectrum DisorderAutistic DisorderBehavior, AnimalDisease Models, AnimalExploratory BehaviorFemaleInhibition, PsychologicalMaleMiceMice, Inbred C57BLNeuronal PlasticityPrefrontal CortexPregnancyPrenatal Exposure Delayed EffectsProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorSocial BehaviorStereotyped BehaviorValproic Acid
2019
Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing
Dedek A, Xu J, Kandegedara CM, Lorenzo LÉ, Godin AG, De Koninck Y, Lombroso PJ, Tsai EC, Hildebrand ME. Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing. Brain 2019, 142: 1535-1546. PMID: 31135041, PMCID: PMC6536915, DOI: 10.1093/brain/awz105.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsLaminae INMDAR responsesDorsal horn synapsesSpinal pain processingNerve injury modelSpinal dorsal hornSynaptic NMDAR responsesTyrosine phosphatase STEP61Loss of inhibitionBehavioral hypersensitivityInflammatory painNeuropathic painDorsal hornPain statesPathological painPain targetsChronic painPain processingInjury modelAssociated downregulationRodent modelsReceptor potentiationPainSTEP61 activity
2018
Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of tic Pathophysiology
Rapanelli M, Frick L, Jindachomthong K, Xu J, Ohtsu H, Nairn A, Pittenger C. Striatal Signaling Regulated by the H3R Histamine Receptor in a Mouse Model of tic Pathophysiology. Neuroscience 2018, 392: 172-179. PMID: 30278251, PMCID: PMC6204318, DOI: 10.1016/j.neuroscience.2018.09.035.Peer-Reviewed Original ResearchConceptsHDC-KO miceMitogen-activated protein kinaseHistamine receptorsWT animalsDorsal striatumH3R activationTic-like movementsStriatonigral medium spiny neuronsAkt phosphorylationMedium spiny neuronsWild-type miceRare genetic causeHistamine dysregulationAgonist treatmentKO miceSpiny neuronsTic disordersTic pathophysiologyStriatal signalingMouse modelNeuropsychiatric diseasesKO modelRepetitive movementsStriatumMiceStriatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2018, 5188-5203. DOI: 10.1007/978-3-319-67199-4_630.Peer-Reviewed Original Research
2017
Glutathione-Responsive Selenosulfide Prodrugs as a Platform Strategy for Potent and Selective Mechanism-Based Inhibition of Protein Tyrosine Phosphatases
Tjin CC, Otley KD, Baguley TD, Kurup P, Xu J, Nairn AC, Lombroso PJ, Ellman JA. Glutathione-Responsive Selenosulfide Prodrugs as a Platform Strategy for Potent and Selective Mechanism-Based Inhibition of Protein Tyrosine Phosphatases. ACS Central Science 2017, 3: 1322-1328. PMID: 29296673, PMCID: PMC5746864, DOI: 10.1021/acscentsci.7b00486.Peer-Reviewed Original ResearchStriatal-enriched protein tyrosine phosphataseProtein tyrosineTyrosine phosphatasePhosphatase inhibitorProtein tyrosine phosphataseProtein tyrosine phosphorylation levelsActive site cysteineProtein tyrosine phosphorylationTyrosine phosphorylation levelsHuman PTPsSite cysteinePTP targetsTyrosine phosphorylationRepresentative cysteine proteaseCysteine proteasesHuman diseasesCellular activitiesPhosphorylation levelsVirulence factorsEssential roleSelective mechanismIntracellular GSH concentrationSelective active sitesNeurodegenerative diseasesPTPSynaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP61
Xu J, Kurup P, Nairn AC, Lombroso PJ. Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP61. Molecular Neurobiology 2017, 55: 3096-3111. PMID: 28466270, PMCID: PMC5668205, DOI: 10.1007/s12035-017-0555-x.Peer-Reviewed Original ResearchConceptsMK-801-treated miceProtein tyrosine Phosphatase 61GluN1/GluN2B receptorsNMDA receptor signalingD-serine treatmentMouse frontal cortexNMDAR signalingSynaptic NMDARsCortical samplesHuman schizophreniaTherapeutic effectFrontal cortexGluN2B receptorsSynaptic plasticityNeurological disordersCognitive deficitsReceptor signalingD-serineSTEP61SchizophreniaBicucullineMiceProteasomal degradationSurface localizationSignaling
2016
Striatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2016, 1-16. DOI: 10.1007/978-1-4614-6438-9_630-1.Peer-Reviewed Original ResearchPotentiation of Synaptic GluN2B NMDAR Currents by Fyn Kinase Is Gated through BDNF-Mediated Disinhibition in Spinal Pain Processing
Hildebrand ME, Xu J, Dedek A, Li Y, Sengar AS, Beggs S, Lombroso PJ, Salter MW. Potentiation of Synaptic GluN2B NMDAR Currents by Fyn Kinase Is Gated through BDNF-Mediated Disinhibition in Spinal Pain Processing. Cell Reports 2016, 17: 2753-2765. PMID: 27926876, DOI: 10.1016/j.celrep.2016.11.024.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsLaminae INeurotrophin brain-derived neurotrophic factorPeripheral nerve injury modelSynaptic N-methyl-D-aspartate receptorsBDNF-TrkB signalingSpinal pain processingNerve injury modelChronic pain statesActivation of TrkBNMDAR dysregulationNMDAR potentiationPain amplificationPain hypersensitivityNeuropathic painPain statesPain processingNeurotrophic factorSpinal neuronsSynaptic excitationSynaptic inhibitionNMDAR currentsInjury modelPotentiation
Academic Achievements & Community Involvement
News
News
- June 17, 2020Source: Yale News
Yale Scientists Propose Explanation For Baffling Form of Childhood OCD
- October 18, 2016
Protein linked to Alzheimer’s may also play a role in schizophrenia
- October 18, 2016
Protein linked to Alzheimer’s may also play a role in schizophrenia
- August 06, 2014
In search for Alzheimer’s drug, a major STEP forward