Dissecting Functional Autoimmunity through High-Resolution Multiomics in a Vitiligo Center of Research Translation (V-CoRT)
白癜风研究转化中心 (V-CoRT) 通过高分辨率多组学剖析功能性自身免疫
基本信息
- 批准号:10703370
- 负责人:
- 金额:$ 166.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-12 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AchievementAdvanced DevelopmentAffectAffinityAntigensArchitectureAtlasesAutoimmuneAutoimmune DiseasesAutoimmunityBiological AssayBiopsyCell CommunicationCell physiologyCellsCellular AssayCenter for Translational Science ActivitiesCharacteristicsClinicalClone CellsCommunicationComplexComputing MethodologiesCuesDataDiseaseDisease ProgressionEnsureEpidermisFluorescent in Situ HybridizationGenetic RiskGoalsHumanInflammationInflammatoryInsulin-Dependent Diabetes MellitusKnowledgeLesionLigandsMapsMemoryModelingMolecularMonitorMultiomic DataMultiple SclerosisOrganPathogenesisPathway interactionsPatientsPigmentsPositioning AttributeRecording of previous eventsResearchResearch PersonnelResolutionSamplingSeriesSignal TransductionSkinStructureT-Cell ReceptorT-LymphocyteTechniquesTestingTherapeuticTissuesTranslatingTranslational ResearchVitiligoWhite Spotsautoreactive T cellcell typechemokinecytotoxic CD8 T cellsdesigndisease phenotypehuman tissueinnovationlong term memorymelanocytemultidisciplinarymultiple omicsnovel therapeutic interventionoutreachreceptorresponserisk variantsingle cell technologyskin disordertooltranscriptomicstranslational goal
项目摘要
OVERALL – PROJECT SUMMARY
Organ-specific autoimmunity requires a series of precise cellular interactions to coordinate target cell destruc-
tion within complex tissues. Vitiligo is an autoimmune disease of the skin in which cytotoxic CD8+ T cells target
pigment-making melanocytes, which results in disfiguring white spots that are particularly devastating for those
with darker skin. Vitiligo is an ideal disease in which to investigate mechanisms of organ-specific autoimmunity
because disease phenotype can be directly correlated to molecular pathways. That is, affected skin can be ob-
served and sampled, target cells and antigens are known, and translational research tools are available. Viti-
ligo shares genetic risk alleles and other mechanisms with autoimmune diseases like type 1 diabetes and mul-
tiple sclerosis, which are more difficult to study in human patients. Through vitiligo we can develop a compre-
hensive understanding of organ-specific autoimmunity as it progresses within human tissue.
Our objective is to determine the mechanisms by which autoreactive T cells navigate the skin, communicate
with neighboring cells, engage and destroy melanocytes, and create long-term memory of autoimmunity di-
rectly within vitiligo lesions. We generated an extensive set of high-resolution, translational multiomics data
from vitiligo patient skin and assembled it into an integrated communication network among multiple cell types
that coordinate disease progression. This provides clues into vitiligo pathogenesis that must now be validated,
dissected, and reassembled to reveal fundamental concepts of autoimmunity. Thus, we hypothesize that auto-
reactive T cell function is carefully coordinated by cellular signals within the microenvironment of the epidermis.
To test this hypothesis, we will leverage existing data, a multidisciplinary team of leading investigators, cutting
edge tools designed for discovery, and an innovative strategy to discover how skin cells coordinate autoim-
munity during vitiligo. Project 1 will investigate Autoreactive T cell Function in Vitiligo to determine how autore-
active T cell clonal diversity and localization define the clinical disease phenotype and coordinate melanocyte
destruction. Project 2 will focus on Cell-Cell Communications and Tissue Memory in Vitiligo to dissect the
mechanisms by which ligand-receptor interactions coordinate T cell localization, function, and inflammatory
memory. These projects will be supported by the High-Resolution Spatial Transcriptomics Research Core us-
ing seq-FISH+ to translate our vitiligo multiomics data into a complete spatial understanding of cellular position
and communication within vitiligo lesions. The Administrative Core will promote communication, ensure scien-
tific achievement, and monitor fiscal management to support focus on research goals and implementation.
We expect to create an integrated understanding of coordinated cellular communications and interactions that
drive vitiligo pathogenesis. This will reveal fundamental mechanisms of autoimmunity and support better thera-
peutic approaches for these devastating diseases. The unique characteristics of vitiligo as well as our prelimi-
nary data, investigative team, and innovative plan provide us with an unparalleled opportunity for discovery.
总体-项目总结
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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John E Harris其他文献
Advancements in Targeted Therapies for Vitiligo: Prioritizing Equity in Drug Development.
白癜风靶向治疗的进展:优先考虑药物开发的公平性。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Camile Delva;Todd F Pearson;John E Harris - 通讯作者:
John E Harris
Characterization of suspended matter in the Gulf of Mexico—II particle size analysis of suspended matter from deep water
- DOI:
10.1016/0146-6291(77)90575-6 - 发表时间:
1977-11-01 - 期刊:
- 影响因子:
- 作者:
John E Harris - 通讯作者:
John E Harris
John E Harris的其他文献
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{{ truncateString('John E Harris', 18)}}的其他基金
Dissecting Functional Autoimmunity through High-Resolution Multiomics in a Vitiligo Center of Research Translation (V-CoRT)
白癜风研究转化中心 (V-CoRT) 通过高分辨率多组学剖析功能性自身免疫
- 批准号:
10404442 - 财政年份:2022
- 资助金额:
$ 166.21万 - 项目类别:
High Resolution Spatial Transcriptomics using seq-FISH+
使用 seq-FISH 进行高分辨率空间转录组学
- 批准号:
10703380 - 财政年份:2022
- 资助金额:
$ 166.21万 - 项目类别:
High Resolution Spatial Transcriptomics using seq-FISH+
使用 seq-FISH 进行高分辨率空间转录组学
- 批准号:
10404444 - 财政年份:2022
- 资助金额:
$ 166.21万 - 项目类别:
Treg Migration and Function During Autoimmunity within Peripheral Tissue
周围组织内自身免疫过程中 Treg 的迁移和功能
- 批准号:
9979628 - 财政年份:2015
- 资助金额:
$ 166.21万 - 项目类别:
Treg Migration and Function During Autoimmunity within Peripheral Tissue
周围组织内自身免疫过程中 Treg 的迁移和功能
- 批准号:
9753126 - 财政年份:2015
- 资助金额:
$ 166.21万 - 项目类别:
Treg Migration and Function During Autoimmunity within Peripheral Tissue
周围组织内自身免疫过程中 Treg 的迁移和功能
- 批准号:
9322541 - 财政年份:2015
- 资助金额:
$ 166.21万 - 项目类别:
Treg Migration and Function During Autoimmunity within Peripheral Tissue
周围组织内自身免疫过程中 Treg 的迁移和功能
- 批准号:
9984020 - 财政年份:2015
- 资助金额:
$ 166.21万 - 项目类别:
Treg Migration and Function During Autoimmunity within Peripheral Tissue
周围组织内自身免疫过程中 Treg 的迁移和功能
- 批准号:
9539195 - 财政年份:2015
- 资助金额:
$ 166.21万 - 项目类别:
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