Clinical-Translational Studies in Skin, Lung, and Vascular Complications in Systemic Sclerosis
系统性硬化症皮肤、肺和血管并发症的临床转化研究
基本信息
- 批准号:10404139
- 负责人:
- 金额:$ 153.48万
- 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:2022-09-20 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-KinaseAffectAnimal ModelAutoimmune DiseasesAutomobile DrivingBinding SitesBioinformaticsBiologicalBiological MarkersBiological ModelsBiologyBiopsyBloodBlood PlateletsBlood VesselsCell CommunicationCell EnergeticsCellsChildhoodChromatinClinicalClinical DataClinical TrialsComplementConnective TissueCutaneous sclerosisDataData SetDatabasesDevelopmentDiseaseDisease MarkerDisease PathwayEpigenetic ProcessFibroblastsFibrosisGene ExpressionGenomicsGlutaminaseGlutamineGoalsHeterogeneityIn VitroInterleukin-6Interstitial Lung DiseasesLeadLocalized sclerodermaLungLung TransplantationLung diseasesMediatingMediator of activation proteinMedical centerMetabolicMetabolismMethodsModelingMolecularMyofibroblastObservational StudyOrganOxidative PhosphorylationPathogenesisPathogenicityPathologic ProcessesPathway interactionsPatientsPerfusionPharmaceutical PreparationsPhenotypePopulationPositioning AttributePositron-Emission TomographyProcessProteomicsProtocols documentationPulmonary FibrosisResearch PersonnelResourcesRheumatologyRoleSerum MarkersSkinSkin TissueSliceSmall Nuclear RNAStructure of parenchyma of lungSystemic SclerodermaSystems BiologyTalentsTestingTissuesTranslational ResearchUniversitiesVacuolar Protein Sortingbiobankbioinformatics toolcell typecollaborative environmentcytokinedrug discoveryepigenomicsexperiencegene discoverygenetic regulatory proteingenomic datahuman diseasehuman tissueimaging approachinhibitorinnovationmacrophagemedical schoolsmultiple omicsnew therapeutic targetnovelnovel markernovel therapeuticspreclinical studyprofibrotic fibroblastprogramsprotein expressionpulmonary arterial hypertensionrepositorysingle cell technologysingle-cell RNA sequencingskin disorderspecific biomarkerstargeted treatmenttherapeutic targettooltranscription factortranscriptometranscriptomicstranslational studyvascular injury
项目摘要
The overall goal of this Center of Research Translation is to utilize biomarker tools and other translational
research observations to discover new therapies for patients with systemic sclerosis (SSc). This goal can be
broken down into four intermediate objectives: understanding pathogenic pathways through translational studies,
identifying informative biomarkers for SSc complications, applying bioinformatics and systems biology
approaches to interpret translational and biomarker data, and developing novel targeted therapeutics. Among
current obstacles to progress in finding new drugs for SSc patients is the continuing limited understanding of
SSc pathogenesis, in part due to its complexity and heterogeneity, and in part due to the lack of good animal
models. The University of Pittsburgh School of Medicine stands in a unique position for informative translational
studies into SSc due to special resources and intellectual talent. It has very large, longitudinal clinical-biological
SSc repositories in rheumatology and pulmonary divisions; it has the only large national experience in single
cell studies in both SSc skin and lungs; it has a strong experience in studying lung proteomics; it has pulmonary
experts in modeling lung disease using in vitro precision cut lung slices and ex vivo lung perfusion; it has a
highly sophisticated program studying pediatric localized scleroderma, as well as pediatric SSc; it has an
experienced and innovative systems biology group; and it has a vigorous drug discovery platform. In Project 1
investigators will expand preliminary observations using single cell RNA-seq, to understand the transcription
factors (TFs) associated with myofibroblast differentiation and discover latent factors/cytokine mediating
macrophage-fibroblast interaction in SSc and pediatric LS. In Project 2 investigators will examine the genomic
and proteomic landscape of patients with SSc-associated interstitial lung disease. Project 2 will also screen
and carry out preclinical studies of Smad3 translocation inhibitors using precision cut lung slices. In Project 3
investigators will study altered platelet energetics and utilize 18F-fluoroglutamine PET imaging to understand
the role of metabolic reprogramming and glutaminolysis in SSc-associated pulmonary arterial hypertension.
Project aims will be supported by two resource cores: a Clinical and Biospecimen Core and a Systems Biology
Core. The former will include collecting comprehensive clinical data, acquiring skin biopsies and lung explant
tissue, and preparing precision cut lung slices. The latter will use a broad range of bioinformatics tools, including
novel methods for detecting stereospecific TF binding sites, and for discovering latent factors mediating cell-
cell interactions in scRNA-seq/multiome datasets. The Systems Biology Core will also synthesize proteomic
and genomic data in project 2, and integrate data from each project and across projects to develop models for
common molecular pathways associated with different disease manifestations. The focus of each of the
projects on different SSc clinical manifestations, mediators of disease, and drug inhibitors will provide a rich,
highly collaborative environment for fundamental discovery within bridging project topics and core resources.
本研究翻译中心的总体目标是利用生物标记工具和其他翻译
项目成果
期刊论文数量(0)
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ROBERT A. LAFYATIS其他文献
ROBERT A. LAFYATIS的其他文献
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{{ truncateString('ROBERT A. LAFYATIS', 18)}}的其他基金
Cell epigenetics & communication in systemic sclerosis and localized scleroderma skin disease
细胞表观遗传学
- 批准号:
10404143 - 财政年份:2022
- 资助金额:
$ 153.48万 - 项目类别:
Cell epigenetics & communication in systemic sclerosis and localized scleroderma skin disease
细胞表观遗传学
- 批准号:
10705648 - 财政年份:2022
- 资助金额:
$ 153.48万 - 项目类别:
Clinical-Translational Studies in Skin, Lung, and Vascular Complications in Systemic Sclerosis
系统性硬化症皮肤、肺和血管并发症的临床转化研究
- 批准号:
10705585 - 财政年份:2022
- 资助金额:
$ 153.48万 - 项目类别:
Open chromatin and transcriptional regulation of dermal myofibroblasts in SSc
SSc 中真皮肌成纤维细胞的开放染色质和转录调控
- 批准号:
9912525 - 财政年份:2019
- 资助金额:
$ 153.48万 - 项目类别:
NIAMS: Center for Research Translation (CORT)
NIAMS:研究翻译中心 (CORT)
- 批准号:
10317277 - 财政年份:2011
- 资助金额:
$ 153.48万 - 项目类别:
Translational studies for identifying and targeting novel pathways in systemic sclerosis pathogenesis
识别和靶向系统性硬化症发病机制新途径的转化研究
- 批准号:
9370321 - 财政年份:2011
- 资助金额:
$ 153.48万 - 项目类别:
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