Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel Disease
识别极早发炎症性肠病的免疫和上皮网络特征
基本信息
- 批准号:10445069
- 负责人:
- 金额:$ 181.58万
- 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:2020-09-15 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:6 year oldAdolescenceAdultAffectAgeAtlasesBioinformaticsBiological Response ModifiersBiopsyBloodBlood specimenBostonCaregiversCellsChildChildhoodClinical DataCollaborationsCollectionCommunitiesComplexCoupledCytometryDataData AnalysesData SetDefectDevelopmentDiagnosisDiseaseEnvironmental HealthEpithelialEpithelial CellsFamily memberFrequenciesGastroenterologyGenerationsGenesGeneticGenomicsGlobal AwarenessGoalsGrantHematopoietic Stem Cell TransplantationImmuneImmune System DiseasesImmune systemImmunologyInflammatory Bowel DiseasesInternationalIntestinesLeadLinkMicrobiologyMissionMolecularMucous MembraneMultiomic DataMutationOrganoidsPathogenesisPathogenicityPathologyPathway AnalysisPatient CarePatient RecruitmentsPatientsPeer ReviewPhenotypePhysiciansPrognostic MarkerProteomicsProtocols documentationPublishingResearchResearch PersonnelSamplingScienceScientistSignal TransductionSiteStandardizationStromal CellsSystems BiologyTechnologyTestingTissuesTranslational ResearchVariantbasecausal variantcell typeclinically relevantdata archivedata resourcedata sharingdesigndiagnostic biomarkerdisease diagnosisearly onsetfunctional genomicsgenetic disorder diagnosisgenetic variantgut microbiomein vitro Modelinnovationintestinal epitheliummembermultiple omicsnew therapeutic targetnext generation sequencingnovelnovel therapeuticspatient orientedperipheral bloodpersonalized carerecruitsingle-cell RNA sequencingstem cell biologytargeted treatmenttherapeutic targettranscriptomicsweb site
项目摘要
Project Summary
Our goal is to build a comprehensive atlas of intestinal epithelial, stromal, and immune cells from both monogenic
and polygenic very early onset inflammatory bowel disease (VEOIBD) patients (0<6 years of age) at the single
cell level by leveraging the diverse expertise of our VEOIBD Consortium (www.veoibd.org). We hypothesize that
developing this atlas will inform upon disease pathogenesis and enable targeted therapeutics for VEOIBD.
Moreover, identification and characterization of novel VEOIBD causative genetic variants will inform upon novel
IBD pathogenic networks extending beyond VEOIBD. We selected key members of our Consortium to facilitate
these goals, including three core patient recruitment sites (Dr. Scott Snapper, Boston; Dr. Christoph Klein,
Munich; Dr. Aleixo Muise Toronto), each with combined expertise in immune phenotyping (Snapper),
transcriptomics (Dr. Snapper, Dr. Alex Shalek, Dr. Ordovas-Montanes, Kean), proteomics (Dr. Mathias Mann),
functional genomics (Drs. Muise, Dr. Klein, Dr. Snapper) as well as expertise in intestinal organoid generation
and functional assessments (Dr. Hans Clevers/Dr. Edward Nieuwenhuis), data analysis/network development
(Dr. Eric Schadt) and data sharing (Dr. Larsson Omberg/Sage Bionetwoks). To generate a VEOIBD cellular and
molecular atlas, our goal is to pursue in VEOIBD patients a multi-omic approach to generate in-depth patient-
specific libraries of data including: 1) single cell and bulk transcriptomic and proteomic data generation from
biopsies; 2) paired single cell and bulk transcriptomics and proteomics from patient-derived organoids; 3) paired
transcriptomics, and proteomics from patient blood. To further inform upon this data set, we will couple these
data with deep immune phenotyping (through mass cytometry) and functional characterization of VEOIBD
patient-derived organoids. In this application, we propose to study 150-200 VEOIBD patients (< 6 years) and 30-
40 age-matched controls employing bulk and single-cell RNA sequencing and proteomics from biopsies and
paired peripheral blood samples. In addition, we will perform deep immune phenotyping on intestinal biopsies
(75-100 patients; 15-20 controls) with paired peripheral blood, as well as organoid development coupled with
bulk and single cell RNA sequencing and functional assessments on 100-150 VEOIBD patients and 20-30
controls. The multitude of cell types in the intestine contributing to disease pathology has to date been mostly
studied in aggregate form. In order to deconvolute the cell specific signal within the tissue and ‘assign’ disease
relevance, we will apply our multiscale network (MultiNet) approaches in combination with single cell omics
technology. Based on the above data sets, we will validate novel VEOIBD causal gene variants which will not
only lead to a better understanding of the disease for these patients but also enhance the development of the
VEOIBD immune atlas and epithelial signature and associated networks. Importantly, we will share these
libraries of data and organoids with the scientific community to accelerate our mission of identifying therapeutic
targets, and cures for VEOIBD.
项目总结
项目成果
期刊论文数量(0)
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Christoph Klein其他文献
Christoph Klein的其他文献
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{{ truncateString('Christoph Klein', 18)}}的其他基金
Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel Disease
识别极早发炎症性肠病的免疫和上皮网络特征
- 批准号:
10670325 - 财政年份:2020
- 资助金额:
$ 181.58万 - 项目类别:
Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel Disease
识别极早发炎症性肠病的免疫和上皮网络特征
- 批准号:
10056563 - 财政年份:2020
- 资助金额:
$ 181.58万 - 项目类别:
Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel Disease
识别极早发炎症性肠病的免疫和上皮网络特征
- 批准号:
10263246 - 财政年份:2020
- 资助金额:
$ 181.58万 - 项目类别:
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