Integrative and trans-ethnic study to understand psoriasis associated signals
了解银屑病相关信号的综合和跨种族研究
基本信息
- 批准号:10657973
- 负责人:
- 金额:$ 37.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-21 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAffectAfrican American populationAfrican ancestryAllelesAmericanBiologicalBiological AssayBiological MarkersBromouridine sequencingCRISPR/Cas technologyCellsChromatinChromosome MappingChronicClinicalComplexDataDevelopmentDirect CostsDiseaseDisease modelEpigenetic ProcessEthnic OriginEtiologyEuropeanFacilities and Administrative CostsFunctional disorderGene FrequencyGeneticGenetic ModelsGenetic TranscriptionGenetic VariationGenetic studyGenomicsGenotypeGoalsHaplotypesHeterogeneityHeterozygoteHi-CIL17 geneImmuneImmune System DiseasesImmune signalingIndividualInflammationInflammatoryInflammatory ResponseMachine LearningMapsMediatingMediatorMissionModelingMolecularMultiomic DataNucleic Acid Regulatory SequencesOutcomePathogenesisPathogenicityPathologicPathologyPathway interactionsPatient-Focused OutcomesPatientsPersonsPharmaceutical PreparationsPlayPopulationPopulation HeterogeneityPredispositionPrevalencePsoriasisPublic HealthQuantitative Trait LociRegulationResearchResolutionResourcesRoleShapesSignal TransductionSkinSusceptibility GeneTNF geneUnited States National Institutes of HealthVariantWorkcausal variantcohortcomorbiditycostcytokinedesigndisease disparitydisease heterogeneityfunctional genomicsgenetic architecturegenetic variantgenome wide association studygenomic datahigh riskhigh throughput technologyhuman diseaseimprovedinflammatory modulationinnovationinter-individual variationinterleukin-23keratinocytemulti-ethnicmultimodalitymultiple omicsprecision medicinepredict clinical outcomepromoterresponseskin disordertranscriptometranscriptomics
项目摘要
PROJECT SUMMARY
Psoriasis is a chronic immune-mediated skin disease that has a significant impact on public health, with annual
direct and indirect costs over $75 billion dollars in the US. Advancements in high throughput technology have
enabled the identification of genetic and genomic components in the Th17/IL-23 and NF𝜅B axes, associated
with psoriasis pathology. Although >80 psoriasis susceptibility regions have been revealed, considerable
challenges remain in narrowing down the causal genetic variations and discerning their pathological mechanisms
that shape disease etiology. Similarly, while NF𝜅B signaling is involved in psoriasis and different skin immune
disorders, we have very limited understanding of the mechanistic role genetic variants play in NF𝜅B regulation.
With the new extended psoriasis GWAS emerging, psoriasis can serve as an ideal skin disease model to study
this phenomenon in keratinocytes. Psoriasis has a prevalence rate of 1.3% among African Americans (AA),
however most US-established genomics studies of psoriasis have been conducted on European American (EA)
populations. Our preliminary data show that the fine-mapping of components can be facilitated by integrating
genetic, epigenetic, and genomic information in a multi-ethnic analysis design, especially when including
individuals with African ancestry. We have illustrated elevated NF𝜅B signaling response in keratinocytes among
AA individuals and that inter-individual variations in inflammatory signature can have significant clinical
implications for the assessment of drug response. The long-term goal of this project is to identify biological
mechanisms for disease heterogeneity among psoriatic patients, and our overall objective is to utilize a trans-
ethnic design to advance the identification of psoriasis-associated regulatory mechanisms involved in the
modulation of NF𝜅B signaling in keratinocytes. We will apply an integrative approach to study multi-omics data
and leverage trans-ethnic information to fine-map the genetic/genomic components associated with inter-
individual inflammatory responses, providing a model to understand disease disparity among psoriatic patients
of different ethnicities. We will i) fine-map the response expression quantitative trait loci (reQTLs) modulating
NF𝜅B and other inflammatory signaling in keratinocytes; ii) determine regulatory mechanisms of psoriasis signal
that drive NF𝜅B signaling in keratinocytes at the cellular level using multi-modal genomic data; iii) utilize genetic
and genomic components participating in NF𝜅B signaling, to model clinical presentations and outcomes for
patients from an ongoing longitudinal psoriasis cohort. Successful completion of the project will have an
important positive impact by providing enhanced resolution and power to identify determinants of inter-individual
variations in inflammatory responses.
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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Lam Cheung Tsoi其他文献
Lam Cheung Tsoi的其他文献
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{{ truncateString('Lam Cheung Tsoi', 18)}}的其他基金
Integrative Biology Approach to Identify and Characterize Roles of lncRNAs Associated with Psoriasis Pathology
识别和表征与银屑病病理学相关的 lncRNA 作用的综合生物学方法
- 批准号:
9371181 - 财政年份:2017
- 资助金额:
$ 37.83万 - 项目类别:
Integrative Biology Approach to Identify and Characterize Roles of lncRNAs Associated with Psoriasis Pathology
识别和表征与银屑病病理学相关的 lncRNA 作用的综合生物学方法
- 批准号:
9761992 - 财政年份:2017
- 资助金额:
$ 37.83万 - 项目类别:
Integrative Biology Approach to Identify and Characterize Roles of lncRNAs Associated with Psoriasis Pathology
识别和表征与银屑病病理学相关的 lncRNA 作用的综合生物学方法
- 批准号:
10246892 - 财政年份:2017
- 资助金额:
$ 37.83万 - 项目类别:
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