Genetic and microbial modifiers of Atopic Dermatitis (AD): Mechanisms of increased AD severity in patients with the R576 polymorphism in IL-4Ra and impact of S aureus skin decolonization on AD
特应性皮炎 (AD) 的遗传和微生物调节剂:IL-4Ra R576 多态性患者 AD 严重程度增加的机制以及金黄色葡萄球菌皮肤去定植对 AD 的影响
基本信息
- 批准号:10381494
- 负责人:
- 金额:$ 52.65万
- 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:2020-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:Academic Medical CentersAdultAffectAllergicAllergic DiseaseAntigensArginineAtopic DermatitisBiological MarkersBiologyBiometryBloodBone MarrowBostonCellsChildChildhoodChimera organismClinicClinicalClinical ResearchClinical TrialsCohort StudiesCutaneousDataDermatologyDevelopmentDiseaseDisease MarkerFinancial HardshipFundingGene ExpressionGeneral HospitalsGenerationsGeneticGenetic PolymorphismGenotypeGlutamineHematopoieticHospitalsHumanHuman ResourcesHypersensitivityImmuneImmunologicsImmunologyInflammationInfrastructureInstitutional Review BoardsInterleukin-13Interleukin-4InvestigationKnowledgeLaboratoriesLaboratory ResearchLinkMassachusettsMechanicsMicrobiologyMorbidity - disease rateMusMutationNational Institute of Allergy and Infectious DiseaseObservational StudyPatient RecruitmentsPatientsPediatric HospitalsPharmaceutical ServicesPopulationPrevalenceProtocols documentationPublic HealthQuality ControlRecordsResearchResearch PersonnelRoleSamplingSeasonsSeveritiesSeverity of illnessShippingSignal TransductionSiteSkinSkin colonizationStaphylococcus aureusTestingTopical applicationTrainingUnited StatesUnited States National Institutes of HealthWomanbaseclinical centerclinical diagnosisdata managementexperiencefundamental researchimprovedinjuredlaboratory facilitymembermicrobialmortalitymouse modelnext generationnovelpatient populationreceptorrecruitrepositoryresearch facilityresponseskin barrierstatistics
项目摘要
This ADRN-CRC application brings together seasoned clinical and laboratory investigators in atopic
dermatitis (AD), with expertise in clinical research, immunology, S aureus biology, dermatology, and statistics.
The investigators have long track records in implementing multi-center and single-center clinical trials and
observational studies in allergic diseases, including AD, to the standards of NIH funded clinical research
networks, in conducting NIH fundamental research on disease mechanisms in AD and in training generations
of investigators in AD research
In part A we demonstrate that we have the personnel and facilities to conduct ADRN network-wide and
CRC center-specific research on pediatric and adult AD patient populations recruited from the allergy and
dermatology clinics at Boston Children's Hospital and collaborating adult centers at the Brigham and Women's
Hospital Mas General Hospital and Boston University Medical Center and Hospital, and from our just
completed, as well as ongoing, NIH-funded studies of schoolchildren with allergic diseases. We have a highly
experienced team, IRB-approved protocols for recruitment and clinical characterization of AD patients, an
infrastructure which includes clinical research facilities, investigational pharmacy services, a laboratory facility
capable of processing, storing and shipping human samples, a state-of-the-art immunology research laboratory
with a 25 year focus on AD, and a data management facility with quality control plans, and capability to upload
data into the NIAID designated repositories and biostatistical support.
Project I in part B will draw on an already genotyped local population of AD patients to test the
hypothesis that the IL-4Rα R576 polymorphism is associated with increased AD severity and alterations in the
function and gene expression of epidermal and immune cells. We will also use a mouse model of AD to test
the hypothesis that both epidermal and immune cells contribute to the increased antigen allergic skin
inflammation observed in mice with the IL-4Rα R576R polymorphism.
Project II in part B will test the hypothesis that S. aureus skin decolonization in AD will reduce disease
severity and favorably alter the function and gene expression of epidermal and immune cells that contribute to
disease severity. We will also test the hypothesis that S. aureus skin colonization promotes the development of
antigen-driven allergic skin inflammation, and its reactivation, using a mouse model of AD.
Our proposal will contribute extensively to the ADRN as a Clinical Research Unit and, as an ADRN-CRC will
help elucidate the role of genetic and microbial modifiers in AD.
!
该ADRN-CRC应用程序汇集了经验丰富的临床和实验室研究人员,
皮肤炎(AD),具有临床研究、免疫学、金黄色葡萄球菌生物学、皮肤病学和统计学方面的专业知识。
研究者在实施多中心和单中心临床试验方面有长期的跟踪记录,
过敏性疾病(包括AD)的观察性研究,符合NIH资助的临床研究标准
网络,在进行国家卫生研究院的基础研究疾病机制在AD和培训一代
AD研究中的研究者
在A部分中,我们证明我们拥有进行ADRN网络范围的人员和设施,
CRC中心针对儿童和成人AD患者人群的研究,招募自过敏和
波士顿儿童医院的皮肤科诊所和布里格姆妇女医院的成人合作中心
医院马斯总医院和波士顿大学医学中心和医院,并从我们的公正
完成的,以及正在进行的,NIH资助的过敏性疾病学童研究。我们有一个高度
经验丰富的团队,IRB批准的AD患者招募和临床表征方案,
基础设施,包括临床研究设施、研究性药房服务、实验室设施
能够处理、储存和运送人类样本,这是一个最先进的免疫学研究实验室,
专注于AD 25年,拥有质量控制计划的数据管理设施,并能够上传
数据输入NIAID指定的储存库和生物统计支持。
项目I的B部分将利用已进行基因分型的当地AD患者人群,
假设IL-4 R α R576多态性与AD严重程度增加和
表皮和免疫细胞的功能和基因表达。我们还将使用AD的小鼠模型来测试
假设表皮细胞和免疫细胞都有助于增加抗原过敏性皮肤
在具有IL-4 R α R576 R多态性的小鼠中观察到炎症。
项目II的B部分将检验S.金黄色皮肤去殖民化在AD将减少疾病
严重性和有利地改变功能和基因表达的表皮和免疫细胞,有助于
疾病严重程度。我们还将检验S.金黄色葡萄球菌皮肤定植促进了
抗原驱动的过敏性皮肤炎症及其再活化,使用AD小鼠模型。
我们的提案将为ADRN作为临床研究单位做出广泛贡献,并且作为ADRN-CRC将
有助于阐明遗传和微生物修饰剂在AD中的作用。
!
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
RAIF SALIM GEHA其他文献
RAIF SALIM GEHA的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('RAIF SALIM GEHA', 18)}}的其他基金
Mechanisms of enhanced food allergy by S. aureus skin colonization in Atopic Dermatitis
特应性皮炎中金黄色葡萄球菌皮肤定植增强食物过敏的机制
- 批准号:
10638821 - 财政年份:2023
- 资助金额:
$ 52.65万 - 项目类别:
Molecular and cellular mechanisms in food anaphylaxis
食物过敏反应的分子和细胞机制
- 批准号:
10408011 - 财政年份:2020
- 资助金额:
$ 52.65万 - 项目类别:
Mechanisms of a Novel Combined Immunodeficiency Caused by a Homozygous Mutation in COPG1
COPG1 纯合突变引起的新型联合免疫缺陷的机制
- 批准号:
10265627 - 财政年份:2020
- 资助金额:
$ 52.65万 - 项目类别:
Molecular and cellular mechanisms in food anaphylaxis
食物过敏反应的分子和细胞机制
- 批准号:
10030396 - 财政年份:2020
- 资助金额:
$ 52.65万 - 项目类别:
Genetic and microbial modifiers of Atopic Dermatitis (AD): Mechanisms of increased AD severity in patients with the R576 polymorphism in IL-4Ra and impact of S aureus skin decolonization on AD
特应性皮炎 (AD) 的遗传和微生物调节剂:IL-4Ra R576 多态性患者 AD 严重程度增加的机制以及金黄色葡萄球菌皮肤去定植对 AD 的影响
- 批准号:
10589788 - 财政年份:2020
- 资助金额:
$ 52.65万 - 项目类别:
Mechanisms of a Novel Combined Immunodeficiency Caused by a Homozygous Mutation in COPG1
COPG1 纯合突变引起的新型联合免疫缺陷的机制
- 批准号:
10159668 - 财政年份:2020
- 资助金额:
$ 52.65万 - 项目类别:
Genetic and microbial modifiers of Atopic Dermatitis (AD): Mechanisms of increased AD severity in patients with the R576 polymorphism in IL-4Ra and impact of S aureus skin decolonization on AD
特应性皮炎 (AD) 的遗传和微生物调节剂:IL-4Ra R576 多态性患者 AD 严重程度增加的机制以及金黄色葡萄球菌皮肤去定植对 AD 的影响
- 批准号:
9974923 - 财政年份:2020
- 资助金额:
$ 52.65万 - 项目类别:
Mechanisms of a Novel Combined Immunodeficiency Caused by a Homozygous Mutation in COPG1
COPG1 纯合突变引起的新型联合免疫缺陷的机制
- 批准号:
10493663 - 财政年份:2018
- 资助金额:
$ 52.65万 - 项目类别:
Mechanisms of a Novel Combined Immunodeficiency Caused by a Homozygous Mutation in COPG1
COPG1 纯合突变引起的新型联合免疫缺陷的机制
- 批准号:
10394995 - 财政年份:2018
- 资助金额:
$ 52.65万 - 项目类别:
Mechanisms of a Novel Combined Immunodeficiency Caused by a Homozygous Mutation in COPG1
COPG1 纯合突变引起的新型联合免疫缺陷的机制
- 批准号:
9912718 - 财政年份:2018
- 资助金额:
$ 52.65万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 52.65万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 52.65万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 52.65万 - 项目类别:
Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 52.65万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 52.65万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 52.65万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 52.65万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 52.65万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 52.65万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 52.65万 - 项目类别:
Grant-in-Aid for Scientific Research (C)