ATOPIC DERMATITIS RESEARCH NETWORK LEADERSHIP CENTER
特应性皮炎研究网络领导中心
基本信息
- 批准号:10610343
- 负责人:
- 金额:$ 36.54万
- 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:2020-04-09 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:Applications GrantsAreaAsthmaAtopic DermatitisBacterial InfectionsBiologicalBirthClinicalClinical ResearchClinical TrialsCohort StudiesCollaborationsCommunicationCutaneousData Coordinating CenterDefectDevelopmentEnsureEpitheliumFood HypersensitivityFunctional disorderFundingGeneral PopulationGoalsGrantHealthHospitalizationHost DefenseHypersensitivityImmuneImmune responseImmunityImpairmentInflammationInfrastructureInterleukin-1Interleukin-13Interleukin-4InterventionIntervention StudiesLeadershipLong-Term EffectsMorbidity - disease rateMulti-site clinical studyNational Institute of Allergy and Infectious DiseaseObservational StudyOperations ResearchOutcomePathway interactionsPatientsPerformancePhenotypeProteomicsProtocols documentationQuality of lifeResearchResearch PersonnelResourcesSamplingSkinStructureStudy SubjectSystems BiologyTherapeutic InterventionTimeTopical CorticosteroidsTranslatingUnited States National Institutes of HealthVirus DiseasesWorkatopybiobankchronic inflammatory skindata integritydesigndysbiosisevidence basefollower of religion Jewishlipidomicsmicrobialmicrobiomemicrobiota transplantationnovelnovel strategiesoperationorganizational structureprogramsresponserhosafety studysingle-cell RNA sequencingskin barrierskin disorderskin microbiomesystemic inflammatory responsetargeted treatmenttranscriptomicstreatment response
项目摘要
PROJECT SUMMARY/ABSTRACT
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. AD is
associated with defective skin barrier function, microbial dysbiosis, as well as various cutaneous immune
abnormalities including type 2 inflammation and decreased cutaneous host defense. These abnormalities
translate into multiple phenotypes and endotypes that are not fully defined and therefore, effective targeted
therapies, beyond type 2 immune blockade, to reverse these various subsets of AD are lacking. Beyond its
effects on cutaneous defense, AD is associated with systemic inflammation and appears to be the first step in
the development of other atopic conditions including food allergy and asthma.
This grant application is being submitted in response to RFA-AI-19-014, Atopic Dermatitis Research
Network-Leadership Center (ADRN-LC). The goal of this proposal is to create an ADRN-LC which will
provide the overall scientific strategy and organizational structure to the ADRN and will interact closely with
the ADRN Clinical Research Centers (ADRN-CRCs), to support the conduct of multi-site clinical studies and
trials that will elucidate mechanisms of skin barrier dysfunction and cutaneous immune responses in
atopic dermatitis (AD).
The central hypothesis in this application is that different phenotypes and endotypes of AD are
associated with distinct defects in their skin barrier, microbiome, and skin immune responses which can
be characterized by novel approaches to skin sampling and open up avenues for paradigm shifting
therapeutic interventions to benefit patients with severe persistent AD. We will achieve our objectives
with the following Aims:
· Specific Aim 1: To establish an Administrative and Clinical Research Operations Leadership
Center that will be responsible for implementation, coordination, and funding of clinical trials and
studies for the ADRN-LC in research areas evaluating mechanism and treatment of AD.
· Specific Aim 2: To develop a Network-wide multi-center ADRN clinical trial to evaluate the long-
term effects of targeted microbiome transplantation on clinical outcomes in AD as well as epithelial
barrier function, microbial dysbiosis, and cutaneous immunity.
· Specific Aim 3: To design a Network-wide ADRN one-year observational study to assess the
stability of AD phenotypes/endotypes using a Network correlation analysis of transcriptomics
(conventional and single cell RNA sequencing), skin tape proteomics, lipidomics, and microbiome
over time in subjects with persistent mild vs. persistent severe AD and assessment of therapeutic
responses to topical corticosteroids and Dupilumab.
· Specific Aim 4: To carry out a Network-wide multi-center ADRN clinical trial to examine the effects
of targeted IL-1 blockade on the clinical outcome, skin microbiome, epithelial skin barrier, and
cutaneous immune response in AD patients who have an inadequate response to IL-4/IL-13 blockade
using Dupilumab therapy.
Accomplishment of these Specific Aims will contribute to novel and important advances in our
understanding of mechanisms of host skin defense and paradigm-shifting treatments of AD. The
establishment of this ADRN-LC will also provide budgetary and scientific resources for the Systems
Biology of Early Atopy Birth Cohort study that is under development by the Consortium for Food Allergy
Research (CoFAR).
项目总结/摘要
特应性皮炎(AD)是普通人群中最常见的慢性炎症性皮肤病。AD是
与缺陷的皮肤屏障功能、微生物生态失调以及各种皮肤免疫相关
异常包括2型炎症和皮肤宿主防御降低。这些异常
转化为多种表型和内型,这些表型和内型尚未完全定义,因此,
除了2型免疫阻断之外,还缺乏逆转AD的这些不同亚群的疗法。超出其
由于AD对皮肤防御的影响,AD与全身性炎症有关,似乎是全身性炎症的第一步。
其他特应性疾病的发展,包括食物过敏和哮喘。
本资助申请是为了响应RFA-AI-19-014,特应性皮炎研究而提交的
网络领导力中心(ADRN-LC)。该提案的目标是建立一个ADRN-LC,
为ADRN提供全面的科学战略和组织结构,并将与
ADRN临床研究中心(ADRN-CRC),以支持多中心临床研究的开展,
这些试验将阐明皮肤屏障功能障碍和皮肤免疫反应的机制,
特应性皮炎(AD)。
本申请中的中心假设是AD的不同表型和内源型是相互关联的。
与皮肤屏障、微生物组和皮肤免疫反应的明显缺陷有关,
以新颖的皮肤采样方法为特征,并为范式转变开辟途径
治疗干预,使重度持续性AD患者受益。我们会实现我们的目标
其目标如下:
·具体目标1:建立行政和临床研究运营领导层
该中心将负责实施、协调和资助临床试验,
ADRN-LC在评估AD机制和治疗的研究领域的研究。
·具体目标2:开展全网络多中心ADRN临床试验,以评估长期
靶向微生物组移植对AD和上皮细胞临床结局的长期影响
屏障功能、微生物生态失调和皮肤免疫。
·具体目标3:设计一项为期一年的全网ADRN观察性研究,以评估
使用转录组学的网络相关性分析的AD表型/内型的稳定性
(常规和单细胞RNA测序)、皮肤带蛋白质组学、脂质组学和微生物组学
持续性轻度与持续性重度AD受试者中随时间的变化以及治疗性
局部皮质类固醇和Dupilumab的反应。
·具体目标4:开展全网络多中心ADRN临床试验,以检查效果
靶向IL-1阻断对临床结果、皮肤微生物组、上皮皮肤屏障和
对IL-4/IL-13阻断反应不足的AD患者的皮肤免疫应答
使用Dupilumab治疗。
这些具体目标的实现将有助于我们的新的和重要的进展,
了解宿主皮肤防御机制和AD的范式转变治疗。的
建立这个ADRN-LC还将为这些系统提供预算和科学资源
食物过敏联合会正在开发的早期特应性畸形出生队列研究的生物学
研究(CoFAR)。
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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DONALD YM LEUNG其他文献
DONALD YM LEUNG的其他文献
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{{ truncateString('DONALD YM LEUNG', 18)}}的其他基金
Experimental and Computational Analysis of the Human Epidemiology and Response to SARS-CoV-2 (HEROS) Cohort
人类流行病学和对 SARS-CoV-2 (HEROS) 队列反应的实验和计算分析
- 批准号:
10359637 - 财政年份:2021
- 资助金额:
$ 36.54万 - 项目类别:
Experimental and Computational Analysis of the Human Epidemiology and Response to SARS-CoV-2 (HEROS) Cohort
人类流行病学和对 SARS-CoV-2 (HEROS) 队列反应的实验和计算分析
- 批准号:
10290261 - 财政年份:2021
- 资助金额:
$ 36.54万 - 项目类别:
ATOPIC DERMATITIS RESEARCH NETWORK LEADERSHIP CENTER
特应性皮炎研究网络领导中心
- 批准号:
9974269 - 财政年份:2020
- 资助金额:
$ 36.54万 - 项目类别:
ATOPIC DERMATITIS RESEARCH NETWORK LEADERSHIP CENTER
特应性皮炎研究网络领导中心
- 批准号:
10662102 - 财政年份:2020
- 资助金额:
$ 36.54万 - 项目类别:
ATOPIC DERMATITIS RESEARCH NETWORK LEADERSHIP CENTER
特应性皮炎研究网络领导中心
- 批准号:
10382408 - 财政年份:2020
- 资助金额:
$ 36.54万 - 项目类别:
National Jewish Health CoFAR Clinical Research Unit
国家犹太健康 CoFAR 临床研究单位
- 批准号:
9882938 - 财政年份:2017
- 资助金额:
$ 36.54万 - 项目类别:
National Jewish Health CoFAR Clinical Research Unit
国家犹太健康 CoFAR 临床研究单位
- 批准号:
10364743 - 财政年份:2017
- 资助金额:
$ 36.54万 - 项目类别:
National Jewish Health CoFAR Clinical Research Unit
国家犹太健康 CoFAR 临床研究单位
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10569513 - 财政年份:2017
- 资助金额:
$ 36.54万 - 项目类别:
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