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immunopathogenesis of NMO-IgG and AQP4-specific T cells in neuromyelitis optica

immunopathogenesis of NMO-IgG and AQP4-specific T cells in neuromyelitis optica
NMO-IgG 和 AQP4 特异性 T 细胞在视神经脊髓炎中的免疫发病机制
批准号:
9262280
负责人:
Michael Levy
金额:
$19.3万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-05-01 至 2019-04-30
关键词:
Adoptive TransferAfrican AmericanAnimal ModelAntibodiesApplications GrantsAstrocytesBasic ScienceBindingBinding SitesBiological MarkersBlindnessBlocking AntibodiesBlood - brain barrier anatomyBrainCell CommunicationCellsChronicClinicClinicalClinical ResearchComplement-Dependent CytotoxicityDiseaseDoctor of PhilosophyEnvironmentEpitopesEthnic OriginExperimental Autoimmune EncephalomyelitisGenetic EngineeringGrantHelper-Inducer T-LymphocyteHospitalsIgG1ImmuneImmune TargetingImmunoglobulin Class SwitchingImmunoglobulin GImmunologic FactorsIncidenceInfiltrationInflammationInflammatoryInflammatory ResponseInjectableInpatientsInstitutesK-Series Research Career ProgramsKnockout MiceMediatingMentorsMentorshipMissionMultiple SclerosisMusNational Institute of Neurological Disorders and StrokeNervous system structureNeuraxisNeurologyNeuromyelitis OpticaOptic NerveOpticsParalysedPathogenesisPathogenicityPathologicPathologyPatientsPeptidesPhenotypePopulationPrevalenceRecruitment ActivityResearchResearch ActivityResearch PersonnelRestRodent ModelRoleScientistSeriesSerologicalServicesSocietiesSpinalSpinal CordStrokeT-Cell Immunologic SpecificityT-LymphocyteTestingTherapeutic InterventionTimeTissuesTranslatingTransverse MyelitisUnited StatesUniversitiesWild Type MouseWorkage groupaquaporin 4body systemdesigndisease phenotypeexperimental studyextracellularfootgranulocyteimmunoreactioninsightnervous system disorderneuroimmunologic diseaseneuroimmunologyneuroinflammationpreventprofessorpublic health relevancerelapse risktargeted treatmentwater channelyoung woman

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DESCRIPTION (provided by applicant): This is a proposal for a 5-year K08 Mentored Clinical Scientist Research Career Development Award from the National Institutes of Neurological Disease and Stroke (NINDS) to investigate the role of NMO-IgG and Aquaporin-4 specific T cells in the immunopathogenesis of neuromyelitis optical. Neuromyelitis optical (NMO) is a devastating neuroinflammatory disorder targeting the optic nerves and spinal cord leading to blindness and paralysis. NMO is associated with a serologic biomarker, the NMO-IgG, which targets the aquaporin-4 (AQP4) water channel on the end feet of astrocytes in the central nervous system. This grant is designed to elucidate the immunopathogenesis of neuromyelitis optical focusing on three aspects: 1. Characterizing the role of the NMO-IgG in inducing or exacerbating the NMO disease phenotype by recruiting granulocytes, 2. Identifying the target of the NMO-IgG on AQP4 in the spinal cord and optic nerves using specific anti-AQP4 antibodies, 3. Evaluating the role of Th17 cells specific for AQP4 in instigating and facilitating inflammation in the central nervous system. Each aim is complimentary to the whole project and will provide unique insights into the pathogenesis of NMO. The principle investigator for this project is Michael Levy, MD, PhD, and an Assistant Professor in the Department of Neurology at the Johns Hopkins University who is working under the mentorship of Peter Calabresi, MD, Professor and Director of the Division of Neuroimmunology at Johns Hopkins University. Dr. Calabresi is a leader in the clinical and research fields of multiple sclerosis and neuroimmunologic diseases. Together in one of the nation's most productive research environments, Dr. Levy will have 75% protected time to spend in the lab and use the rest of the time to translate his basic science work to the bedside in the NMO clinic and on the inpatient neurology service at Johns Hopkins Hospital.
期刊论文(19)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1111/cen3.12458
发表时间: 2018-08
期刊: Clinical & experimental neuroimmunology
影响因子: --
作者: [Holroyd KB, Aziz F, Szolics M, Alsaadi T, Levy M, Schiess N]
通讯作者: Schiess N
DOI: 10.1186/s40478-015-0207-1
发表时间: 2015-05-21
期刊: Acta neuropathologica communications
影响因子: 7.1
作者: [Jones MV, Huang H, Calabresi PA, Levy M]
通讯作者: Levy M
DOI: 10.1111/cen3.12239
发表时间: 2015-11-01
期刊: Clinical & experimental neuroimmunology
影响因子: --
作者: [Mealy MA, Shin K, John G, Levy M]
通讯作者: Levy M
DOI: 10.1016/j.jns.2015.05.013
发表时间: 2015-08-15
期刊: JOURNAL OF THE NEUROLOGICAL SCIENCES
影响因子: 4.4
作者: [Mealy, Maureen A., Whetstone, Anna, Orman, Gunes, Izbudak, Izlem, Calabresi, Peter A., Levy, Michael]
通讯作者: Levy, Michael
16
    The Immunopathogenesis of Familial Transverse Myelitis Due to Mutations in VPS37a
    • 批准号:
      10658427
    • 项目类别:
    • 资助金额:
      $41.75万
    • 财政年份:
      2023
    • 负责人:
      Michael Levy
    • 依托单位:
    Developing Tolerization Therapies from a New T-cell Based Mouse Model of Neuromyelitis Optica
    • 批准号:
      10396470
    • 项目类别:
    • 资助金额:
      $39.62万
    • 财政年份:
      2018
    • 负责人:
      Michael Levy
    • 依托单位:
    Developing Tolerization Therapies from a New T-cell Based Mouse Model of Neuromyelitis Optica
    • 批准号:
      9919500
    • 项目类别:
    • 资助金额:
      $39.62万
    • 财政年份:
      2018
    • 负责人:
      Michael Levy
    • 依托单位:
    immunopathogenesis of NMO-IgG and AQP4-specific T cells in neuromyelitis optica
    • 批准号:
      8653032
    • 项目类别:
    • 资助金额:
      $19.3万
    • 财政年份:
      2013
    • 负责人:
      Michael Levy
    • 依托单位:
    海外基金