The Role of B cells in the Origin and Progression of Multiple Sclerosis
B 细胞在多发性硬化症的起源和进展中的作用
基本信息
- 批准号:10605298
- 负责人:
- 金额:$ 112.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAntibodiesAxonB-LymphocytesBrain imagingCNS autoimmune diseaseCellsCellular biologyCerebrospinal FluidChronicClinicalDataDiseaseDisease ProgressionElementsFingerprintGenetic DeterminismGoalsHumanIndividualInflammationMagnetic Resonance ImagingMediatingMolecularMultiple SclerosisMyelinNeurologic DysfunctionsNeuronsOligodendrogliaOnset of illnessPathogenicityPathologyPatient-Focused OutcomesPatientsPhage DisplayPharmaceutical PreparationsPlayPopulationProgressive DiseaseProtein ArrayProteinsRecombinant AntibodyResearchRoleSerial Magnetic Resonance ImagingSerumSpinal CordTechniquesTechnologyTherapeuticUnited StatesViralantibody librariesbiobankchronic autoimmune diseasecohortfallsgenetic informationimprovedinformation organizationmicrobialnovelperipheral bloodreceptorscreeningsynthetic proteintooltranscriptomics
项目摘要
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system affecting nearly one
million individuals in the United States. The disease is characterized by acute and chronic inflammation, myelin
loss; oligodendrocyte, neuronal and axonal pathology; and progressive neurological dysfunction. A number of
breakthrough translational discoveries, and especially the highly beneficial effects of B cell depleting drugs, have
set the stage for a growing, yet still imperfect, therapeutic pipeline. Research will fall short of its potential to
improve patient outcomes until the trigger(s) of disease onset and modifiers of progression are identified.
Central to this project is the hypothesis that B cells presenting in the cerebrospinal fluid (CSF) and peripheral
blood during early MS play key roles in triggering MS and in mediating ongoing progressive disease activity. We
propose to interrogate unique patient cohorts, including an incident cohort, with novel enabling technologies to
identify triggers of MS and modifiers of the clinical course. Well characterized clinical populations, high-field
serial magnetic resonance imaging (MRI), genetic information organized as functional operational networks, and
a focus on B cell biology are the central elements of this initiative. A primary goal will be to characterize the
molecular diversity of B cells and their receptors at various stages of disease to identify pathogenic populations
and their antigenic targets.
A multi-layered experimental strategy includes single cell B cell transcriptomics, together with comprehensive
phage-displayed synthetic human, viral and microbial peptidomes for the screening of antibody fingerprints
against external drivers in the serum, CSF, and recombinant antibody libraries. The integrative analysis will
contextualize the data using clinical, MRI and genetic determinants, striving to apply rigorous statistical
principles, including independent replication.
多发性硬化症(MS)是一种慢性自身免疫性疾病的中枢神经系统影响近一个
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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STEPHEN L HAUSER其他文献
STEPHEN L HAUSER的其他文献
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{{ truncateString('STEPHEN L HAUSER', 18)}}的其他基金
The Role of B cells in the Origin and Progression of Multiple Sclerosis
B 细胞在多发性硬化症的起源和进展中的作用
- 批准号:
10401443 - 财政年份:2019
- 资助金额:
$ 112.92万 - 项目类别:
The Role of B cells in the Origin and Progression of Multiple Sclerosis
B 细胞在多发性硬化症的起源和进展中的作用
- 批准号:
9923778 - 财政年份:2019
- 资助金额:
$ 112.92万 - 项目类别:
Disease relevance of CD20 expression on T cells in multiple sclerosis patients
多发性硬化症患者 T 细胞 CD20 表达的疾病相关性
- 批准号:
8945644 - 财政年份:2015
- 资助金额:
$ 112.92万 - 项目类别:
Disease relevance of CD20 expression on T cells in multiple sclerosis patients
多发性硬化症患者 T 细胞 CD20 表达的疾病相关性
- 批准号:
9127811 - 财政年份:2015
- 资助金额:
$ 112.92万 - 项目类别:
Disease relevance of CD20 expression on T cells in multiple sclerosis patients
多发性硬化症患者 T 细胞 CD20 表达的疾病相关性
- 批准号:
9306228 - 财政年份:2015
- 资助金额:
$ 112.92万 - 项目类别:
Educating Physician-Neuroscientists: The R25 at UCSF
教育医师神经科学家:UCSF 的 R25
- 批准号:
8244469 - 财政年份:2010
- 资助金额:
$ 112.92万 - 项目类别:
Educating Physician-Neuroscientists: The R25 at UCSF
教育医师神经科学家:UCSF 的 R25
- 批准号:
8234664 - 财政年份:2010
- 资助金额:
$ 112.92万 - 项目类别:
Educating Physician-Neuroscientists: The R25 at UCSF
教育医师神经科学家:UCSF 的 R25
- 批准号:
8855839 - 财政年份:2010
- 资助金额:
$ 112.92万 - 项目类别:
Educating Physician-Neuroscientists: The R25 at UCSF
教育医师神经科学家:UCSF 的 R25
- 批准号:
9308006 - 财政年份:2010
- 资助金额:
$ 112.92万 - 项目类别:
Educating Physician-Neuroscientists: The R25 at UCSF
教育医师神经科学家:UCSF 的 R25
- 批准号:
8839348 - 财政年份:2010
- 资助金额:
$ 112.92万 - 项目类别:
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