Measurement and Prediction of Endothelial Cross-family Signaling
内皮跨家族信号传导的测量和预测
基本信息
- 批准号:10689341
- 负责人:
- 金额:$ 66.47万
- 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:2022-09-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:Adaptor Signaling ProteinAdipocytesAdipose tissueAffinityAmino AcidsAreaBindingBlood VesselsCategoriesCell ProliferationCell SurvivalCell physiologyCellsComputer ModelsDataDevelopmentDirected Molecular EvolutionDiseaseDisease ProgressionDoseEffector CellEndothelial CellsEndothelial Growth Factors ReceptorEndotheliumEngineeringFamilyFibrinogenFibroblastsFibrosisGoalsGrowth FactorGrowth Factor InhibitionGrowth Factor ReceptorsHealthHumanIn VitroInflammationInsulin ResistanceKDR geneKnowledgeLeadLibrariesLigandsLipidsMalignant NeoplasmsMeasurementMeasuresMediatingMedicineModelingMolecularNational Heart, Lung, and Blood InstituteObesityOrganoidsPTK2 genePathogenicityPermeabilityPhosphorylationPlatelet Activating FactorPlatelet-Derived Growth FactorPlatelet-Derived Growth Factor ReceptorPre-Clinical ModelPredictive FactorProcessProliferatingPropertyProteinsReceptor ActivationRegulationResearchRoleSchemeSignal TransductionSiteStructureSystemSystems BiologyTestingTherapeuticThymidine PhosphorylaseTissue ExpansionTissuesTranslatingTyrosineValidationVascular DiseasesVascular Endothelial Growth FactorsVascularizationWorkangiogenesisdesignexperimental analysisin silicoinnovationkinetic modelmembermigrationmolecular dynamicsmutation screeningnovelnovel strategiesobesity treatmentobesogenicpedagogypre-clinicalprotein structurereceptorreceptor bindingresponsescreeningsimulationtext searchingtheories
项目摘要
PROJECT SUMMARY/ABSTRACT
The vascular endothelial growth factors (VEGFs) direct key signaling processes in obesity and at least 70 other diseases.
However, focus on this signaling node alone has not achieved the promise of predictable angiogenic control. Current models
are incomplete as other growth factors, besides VEGF, contribute to vascular disease progression, presenting a complexity
that cannot be predictably regulated by targeting one node in this system. Therefore, there is a continuing need to account
for the complexity of additional, multi-component signaling networks, a goal that can be achieved via data-driven,
computational systems biology in close concert with experimental analysis of signaling and functional response.
Toward this goal, we aim to examine a novel paradigm of network regulation called cross-family signaling, in which
members from one growth factor family [e.g., platelet derived growth factors (PDGFs)] bind to and signal through members
of another family (e.g., VEGFRs). We hypothesize that systematic examination of protein structure and downstream
signaling within the cross-family paradigm via simulation, ligand-engineering, network quantification, and computational
modeling can uncover novel mechanisms to control angiogenesis. We will test this hypothesis through three aims,
sensitively quantifying receptor activation rates and functional responses of cross-family binding (e.g., proliferation,
migration, and barrier function); predicting and measuring the structural properties of cross-family binding via molecular
simulations and directed evolution; and developing validated deterministic models (mass-action kinetic modeling) of cross-
family signaling and applying them to study and control the dynamics of cross-family signaling in human cell systems, in
silico.
We are primed to lead this new research because we are among the first to pursue this important theoretical paradigm, and
we lead this cause to understand cell signaling via structure/function–based computational modeling. This work will
catalyze a shift in perspective and innovation in the areas of cell signaling, systems biology, and predictive design of obesity-
focused therapies.
项目总结/文摘
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Quantification of surface-localized and total oxytocin receptor in myometrial smooth muscle cells
- DOI:10.1016/j.heliyon.2024.e25761
- 发表时间:2024-02-15
- 期刊:
- 影响因子:4
- 作者:Fang,Yingye;Reinl,Erin L.;Imoukhuede,Princess I.
- 通讯作者:Imoukhuede,Princess I.
Absolute Quantification of Plasma Membrane Receptors Via Quantitative Flow Cytometry.
- DOI:10.1007/978-1-0716-2217-9_4
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Axl and Vascular Endothelial Growth Factor Receptors Exhibit Variations in Membrane Localization and Heterogeneity Across Monolayer and Spheroid High-Grade Serous Ovarian Cancer Models
- DOI:10.1089/genbio.2022.0034
- 发表时间:2023-02-01
- 期刊:
- 影响因子:0
- 作者:Fang, Yingye;Imoukhuede, Princess I.
- 通讯作者:Imoukhuede, Princess I.
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Princess Izevbua Imoukhuede其他文献
Princess Izevbua Imoukhuede的其他文献
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{{ truncateString('Princess Izevbua Imoukhuede', 18)}}的其他基金
Measurement and Prediction of Endothelial Cross-family Signaling
内皮跨家族信号传导的测量和预测
- 批准号:
10672552 - 财政年份:2022
- 资助金额:
$ 66.47万 - 项目类别:
Systems analysis and prediction of endothelial cross-family signaling
内皮跨家族信号传导的系统分析和预测
- 批准号:
10317179 - 财政年份:2021
- 资助金额:
$ 66.47万 - 项目类别:
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