Integrated genetic, omic, and immunologic studies to identify endotypes and novel drug targets for asthma and allergic diseases
综合遗传、组学和免疫学研究,以确定哮喘和过敏性疾病的内型和新药物靶点
基本信息
- 批准号:10261987
- 负责人:
- 金额:$ 139.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-19 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAffectAllergic DiseaseAllergic rhinitisAsthmaBacterial Artificial ChromosomesBiologicalBiologyBirthCategoriesCell physiologyCellsChildChronic DiseaseClinicalDataDevelopmentDiagnosisDiseaseEngineeringEnhancersEnvironmentEnvironmental ExposureEpithelialEpithelial CellsEthnic groupFood HypersensitivityGenesGeneticGenetic RiskGenomicsGoalsHealth Care CostsHealthcare SystemsHeritabilityHumanHypersensitivityImmuneImmunologicsImmunologyIndividualInfrastructureKnowledgeLinkLungLymphocyteMapsMolecularMyeloid CellsOutcomePathogenesisPeripheralPhenotypeProcessQuantitative Trait LociReportingResearch PersonnelResourcesRestRiskRoleServicesSmooth MuscleSpecificityTechnologyTestingTherapeuticTissuesTranslationsVariantWorkbiobankbronchial epitheliumcausal variantcell typeclinical heterogeneityclinical phenotypecohortcostdata managementdisease heterogeneitydisorder riskethnic diversitygene discoverygene functiongenome wide association studygenome-widemouse modelmulti-ethnicnew therapeutic targetnovelpersonalized medicineprecision medicineprogramsrespiratory smooth musclerisk variantskin hypersensitivitytherapeutic targettooltraittranscriptome sequencing
项目摘要
ABSTRACT
Asthma and allergic diseases are among the most common chronic diseases in children and adults, costing
our health care system over $80 billion per year. Rates have been increasing over the past 40 years and
therapeutic advances have been incremental. Over 150 loci have been reported in large genome-wide
association studies (GWAS) of asthma and allergic diseases, but their individual effects are small and these
variants account a small fraction of the overall genetic risk. Moreover, remarkably few of the GWAS findings for
asthma and allergic diseases have led to discoveries of causal variants or causal genes that contribute to
asthma and allergic disease pathogenesis. The latter has been particularly challenging due in part to the
significant clinical heterogeneity of these diseases, and in part to the lag in the development of powerful
statistical, molecular, and immunologic tools for bridging the trajectory from GWAS to gene discovery to
biology to translation. In this application, we propose a robust and comprehensive strategy for identifying
candidate causal variants and their target genes at asthma and allergic disease-associated loci, and for
characterizing (i) their functional effects in asthma and allergic disease-relevant cells types, including bronchial
epithelial cells, airway smooth muscle and lung immune cells, as well as peripheral immune cells, all in resting
and activated states; (ii) their downstream phenotypic effects on both broad categories of disease groups and
traits in the UK Biobank resource and on specific asthma and allergic disease endotypes in deeply phenotyped
ethnically-diverse subjects participating in asthma birth cohorts; and (iii) their immunologic effects in resting
and activated lung lymphocytes and myeloid cells and in “humanized locus” BAC-engineered mouse models.
These goals will be accomplished through a highly collaborative and synergistic program that includes two
projects, a service core, and an administrative core that together will that bridge the trajectory from GWAS to
translation through highly integrated studies by an exceptional team of investigators with expertise in genetics,
(epi)genomics, statistical genetics, and immunology. Achieving these goals will ultimately identify novel drug
targets and the individuals most likely to respond, providing a framework for precision medicine and
personalized treatment of asthma and allergic diseases.
摘要
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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Marcelo A. Nobrega其他文献
Upregulation of emSYNGAP1/em expression in mice and human neurons by redirecting alternative splicing
通过重定向可变剪接来上调小鼠和人类神经元中 emSYNGAP1/em 的表达
- DOI:
10.1016/j.neuron.2023.02.021 - 发表时间:
2023-05-17 - 期刊:
- 影响因子:15.000
- 作者:
Runwei Yang;Xinran Feng;Alejandra Arias-Cavieres;Robin M. Mitchell;Ashleigh Polo;Kaining Hu;Rong Zhong;Cai Qi;Rachel S. Zhang;Nathaniel Westneat;Cristabel A. Portillo;Marcelo A. Nobrega;Christian Hansel;Alfredo J. Garcia III;Xiaochang Zhang - 通讯作者:
Xiaochang Zhang
Enhancers: five essential questions
增强子:五个关键问题
- DOI:
10.1038/nrg3458 - 发表时间:
2013-03-18 - 期刊:
- 影响因子:52.000
- 作者:
Len A. Pennacchio;Wendy Bickmore;Ann Dean;Marcelo A. Nobrega;Gill Bejerano - 通讯作者:
Gill Bejerano
Upregulation of emSYNGAP1/em expression in mice and human neurons by redirecting alternative splicing
通过重定向可变剪接来上调小鼠和人类神经元中 emSYNGAP1/em 的表达
- DOI:
10.1016/j.neuron.2023.02.021 - 发表时间:
2023-05-17 - 期刊:
- 影响因子:15.000
- 作者:
Runwei Yang;Xinran Feng;Alejandra Arias-Cavieres;Robin M. Mitchell;Ashleigh Polo;Kaining Hu;Rong Zhong;Cai Qi;Rachel S. Zhang;Nathaniel Westneat;Cristabel A. Portillo;Marcelo A. Nobrega;Christian Hansel;Alfredo J. Garcia III;Xiaochang Zhang - 通讯作者:
Xiaochang Zhang
Comparative genomics at the vertebrate extremes
脊椎动物极端情况下的比较基因组学
- DOI:
10.1038/nrg1350 - 发表时间:
2004-06-01 - 期刊:
- 影响因子:52.000
- 作者:
Dario Boffelli;Marcelo A. Nobrega;Edward M. Rubin - 通讯作者:
Edward M. Rubin
Marcelo A. Nobrega的其他文献
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{{ truncateString('Marcelo A. Nobrega', 18)}}的其他基金
Integrated genetic, omic, and immunologic studies to identify endotypes and novel drug targets for asthma and allergic diseases
综合遗传、组学和免疫学研究,以确定哮喘和过敏性疾病的内型和新药物靶点
- 批准号:
10453773 - 财政年份:2021
- 资助金额:
$ 139.17万 - 项目类别:
Integrated genetic, omic, and immunologic studies to identify endotypes and novel drug targets for asthma and allergic diseases
综合遗传、组学和免疫学研究,以确定哮喘和过敏性疾病的内型和新药物靶点
- 批准号:
10615778 - 财政年份:2021
- 资助金额:
$ 139.17万 - 项目类别:
Functional Genomics of IL-33 expression and asthma risk
IL-33 表达和哮喘风险的功能基因组学
- 批准号:
9247245 - 财政年份:2014
- 资助金额:
$ 139.17万 - 项目类别:
Functional Genomics of IL-33 expression and asthma risk
IL-33 表达和哮喘风险的功能基因组学
- 批准号:
8721683 - 财政年份:2014
- 资助金额:
$ 139.17万 - 项目类别:
Functional Genomics of IL-33 Expression and Asthma Risk
IL-33 表达和哮喘风险的功能基因组学
- 批准号:
9281175 - 财政年份:2014
- 资助金额:
$ 139.17万 - 项目类别:
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