Transcriptomics of Pain in Sickle Cell Disease
镰状细胞病疼痛的转录组学
基本信息
- 批准号:10501596
- 负责人:
- 金额:$ 39.62万
- 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:2022-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAcute PainAddressAdhesionsAdultAffectAmericanBiological MarkersBlood CellsCaringCellsChildhoodChronicCollectionDataDevelopmentDrug TargetingEndotheliumErythrocytesErythroidErythroid CellsEtiologyEventExhibitsExposure toFrequenciesGenesGenetic TranscriptionGenomeGenomicsGerm-Line MutationGoalsHemolytic AnemiaHospitalsHyperalgesiaImpairmentIndividualInheritedInjuryIschemiaLeadLeukocytesLinkNatureNociceptionOpioidPTPRC genePainPain MeasurementPain NaturePathway interactionsPatientsPhenotypePredispositionProviderPublishingQuality of lifeRNARecording of previous eventsResolutionRiskRisk FactorsSamplingSickle Cell AnemiaSomatic MutationTFRC geneTestingVariantWorkacute carecandidate markercell typechronic painchronic pain managementchronic pain patientclinical painclinically relevantcohortdiagnostic biomarkerdifferential expressionendogenous opioidsexperiencegenetic variantgenome sequencinggenomic datagenomic variationimprovedindividual variationinnovationmetabolomicsmethylomicsmultiple omicsnovel therapeuticsopioid overusepediatric patientsprecision medicinepreventsicklingtargeted biomarkertargeted treatmenttherapeutic targettranscriptometranscriptome sequencingtranscriptomicsvaso-occlusive crisiswhole genome
项目摘要
PROJECT SUMMARY/ABSTRACT
Patients with sickle cell disease (SCD) exhibit marked inter-individual heterogeneity in frequency
of acute pain events, or vaso-occlusive crises (VOC) and development of chronic pain. The nidus
of a VOC is typically the adhesion of a leukocyte to the endothelium, bringing with it a red cell
which deoxygenates and sickles, resulting in vaso-occlusion, ischemia, and pain. We therefore
collected SCD patient RNA from CD71+ cells (red cell precursors that still retain RNA) and
CD45+, leukocytes from individuals with and without chronic pain, and longitudinal collections
obtained at steady state, in VOC, and VOC resolution, and submitted these samples to TOPMed
for RNASeq analysis. We propose to leverage this transcriptome data from a well phenotyped
pediatric SCD cohort to address the unmet need of objective, quantifiable markers of acute and
chronic pain, and evaluate in the context of the germline and somatic mutations found in the same
subjects’ whole genome sequencing (WGS) data, also in TOPMed. Short term goals are to 1)
identify genes and pathways altered in the chronic pain state, 2) identify transcriptome changes
associated with pain events and their resolution, 3) generate a transcriptional risk score for the
development of chronic pain, and 4) determine which variants associated with chronic pain
development are likely to be causative through transcriptome wide association studies. Long
term goals are to use these findings to 1) develop targeted therapies to prevent and treat VOC,
2) therapies to treat chronic pain in SCD, and 3) biomarkers to distinguish acute pain events from
chronic pain. The ability to do so will allow providers to manage VOC appropriately and
aggressively, without inadvertently confusing chronic pain with an acute pain episode. Our
inability to distinguish between acute and chronic pain harms our patients, as the opioids that are
the mainstay for VOC treatment often worsen chronic pain through opioid induced hyperalgesia.
Our work will leverage TOPMed samples via our innovative transcriptomics analysis to identify
risk factors, therapeutic targets, and biomarkers of chronic pain, in order to improve the care and
quality of life of individuals living with SCD.
项目总结/文摘
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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Vivien Andrea Sheehan其他文献
Vivien Andrea Sheehan的其他文献
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{{ truncateString('Vivien Andrea Sheehan', 18)}}的其他基金
Basic and Translational Mechanisms of Alloimmunization to RBC Transfusion Scientific Core A
红细胞输血同种免疫的基本和转化机制 科学核心 A
- 批准号:
10711667 - 财政年份:2023
- 资助金额:
$ 39.62万 - 项目类别:
Basic and Translational Mechanisms of Alloimmunization to RBC Transfusion. Project 4
红细胞输注同种免疫的基本和转化机制。
- 批准号:
10711671 - 财政年份:2023
- 资助金额:
$ 39.62万 - 项目类别:
A Genomics Approach to Gamma-Globin Regulation
伽马珠蛋白调控的基因组学方法
- 批准号:
9164151 - 财政年份:2016
- 资助金额:
$ 39.62万 - 项目类别:
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