Computational Analysis of CD8 T Cells Using Single Cell Sequencing
使用单细胞测序对 CD8 T 细胞进行计算分析
基本信息
- 批准号:9981905
- 负责人:
- 金额:$ 11.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-09 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptive TransferAffectAmericanAtypical lymphocyteAutoimmune DiseasesAutoimmune ProcessAutoimmune hemolytic anemiaAutoimmunityAutomobile DrivingBiologicalCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneChronicComplexComputer AnalysisDataData SetDefectDevelopmentDiseaseDisease OutcomeDisease ProgressionDisease modelEvaluationEventExhibitsExperimental ModelsGene DeletionGene ExpressionGenesGoalsImmuneImmune TargetingImmune responseIndividualInfectionInflammationInterleukin-2KineticsKnockout MiceKnowledgeLupusMapsMathematicsModelingMusMutationNatureOnset of illnessPancreatitisPancytopeniaPathogenesisPathologyPathway interactionsPatientsPatternProcessPublishingRegulatory T-LymphocyteT cell differentiationT cell responseT-Lymphocyte SubsetsTestingTimeTissuesValidationbaseclinically relevanteffector T cellgenetic signaturein vivoinnovationmathematical methodsmathematical modelmouse modelpreventreaction ratesingle cell sequencingstoichiometrysystemic autoimmunitytranscriptome sequencing
项目摘要
PROJECT SUMMARY
Autoimmunity is a complex disorder affecting over 20 million Americans. Unveiling the multi-step process
leading to autoimmunity and ultimately the ability to effectively treat disease requires an in-depth
understanding of the self-reactive lymphocytes and the mechanisms by which they evade tolerance and
promote destruction of self-tissue. Although there has been a large accumulation of quantitative data on the
dynamics of CD8 T cell responses following infection, much less is known about how naive CD8 T cells
differentiate into various effector pathways, nor about global CD8 T cell gene expression changes during
autoimmune disease. Our proposal seeks to combine experimental, computational and mathematical
approaches to understand the initiation and development of autoimmune disease by analysis of CD8 T cells.
Using well-characterized, tractable experimental models of autoimmune disease, we will test, refine and
validate previously published CD4 T cell differentiation mathematical models to develop a model of CD8 T cell
differentiation and dysregulation during the autoimmune disease process. Aim 1 will quantitatively define the
gene expression kinetics in spontaneous autoimmune models with multiple disease manifestations. In Aim 2
we will expand this evaluation to several autoimmune models with some overlapping and distinct autoimmune
disease outcomes to systematically define the genes and pathways that underlie immune abnormalities critical
to the development of individual diseases and those that underlie multiple diseases. We will further compare
these data to published patient data to focus on clinically relevant genes. In Aim 3 we will combine the results
of Aim 1 and 2 to mathematically model CD8 T cell gene expression kinetics, and validate this model using
mouse in vivo disease studies. This mathematical model will enable us to predict the gene signatures driving
CD8 T cell fate choices and triggering autoimmunity.
项目总结
项目成果
期刊论文数量(1)
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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Katrina K Hoyer其他文献
Katrina K Hoyer的其他文献
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{{ truncateString('Katrina K Hoyer', 18)}}的其他基金
Regulatory T cell function in predicting Valley fever outcomes
调节性 T 细胞功能预测谷热结果
- 批准号:
9979119 - 财政年份:2020
- 资助金额:
$ 11.06万 - 项目类别:
Cytokine Dysregulation in Autoimmune Hemolytic Anemia
自身免疫性溶血性贫血中的细胞因子失调
- 批准号:
7586913 - 财政年份:2009
- 资助金额:
$ 11.06万 - 项目类别:
Cytokine Dysregulation in Autoimmune Hemolytic Anemia
自身免疫性溶血性贫血中的细胞因子失调
- 批准号:
8464352 - 财政年份:2009
- 资助金额:
$ 11.06万 - 项目类别:
Cytokine Dysregulation in Autoimmune Hemolytic Anemia
自身免疫性溶血性贫血中的细胞因子失调
- 批准号:
8532955 - 财政年份:2009
- 资助金额:
$ 11.06万 - 项目类别:
Cytokine Dysregulation in Autoimmune Hemolytic Anemia
自身免疫性溶血性贫血中的细胞因子失调
- 批准号:
8704770 - 财政年份:2009
- 资助金额:
$ 11.06万 - 项目类别:
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