Pathogenesis of Thrombotic Microangiopathy
Pathogenesis of Thrombotic Microangiopathy
批准号:
9139498
负责人:
X. Long Zheng
金额:
$45.54万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-09-14 至 2019-03-31
关键词:
AdhesivesAffectAgeAmino AcidsAntibodiesBindingBinding SitesBiological AssayBiological ProcessBlood CirculationBlood Coagulation DisordersBlood capillariesC-terminalCleaved cellClinicalCodeComplementComplement 3bComplement ActivationComplement Factor HCoupledDataDefectDeuteriumDevelopmentDiseaseDisease ProgressionEndothelial CellsEnzyme-Linked Immunosorbent AssayEventF8 geneFactor VIIIFibrinogenGenesGeneticGenetic PolymorphismHealthHemolytic-Uremic SyndromeHemostatic functionHistologyHumanHydrogenImmunohistochemistryInheritedInvestigationKineticsLaboratoriesLeadLightLiquid substanceMass Spectrum AnalysisMediatingMetalloproteasesMonoclonal AntibodiesMusMutateMutationOrganOutcomePathogenesisPathologyPatientsPhysiologicalPlasmaPlatelet GlycoproteinsPositioning AttributePredispositionPrevalencePreventionProcessProteolysisProteolytic ProcessingReactionRecombinantsRecoveryRegulationResolutionRoleSerine ProteaseSyndromeTestingThrombosisThrombotic Thrombocytopenic PurpuraThrombusTitrationsTransgenic MiceUncertaintyWild Type Mousearteriolecapillaryclinical phenotypeefficacy testingexperiencein vivoinhibitor/antagonistmouse modelmutantnovel therapeuticspreventsexshear stresstoolvon Willebrand Diseasevon Willebrand Factor
中文摘要
英文摘要
DESCRIPTION (provided by applicant): Deficiency of plasma ADAMTS13 activity, either hereditary or acquired, causes thrombotic thrombocytopenic purpura (TTP). However, the triggering events and mechanisms underlying the pathogenesis of TTP are not fully understood. Emerging data suggest that complement activation may be associated with both hemolytic uremic syndrome (HUS) and TTP. In Aim 1, we propose to determine the effects of CFH on ADAMTS13- mediated VWF proteolysis and its adhesive function under flow. We will also determine the kinetics and mechanism of such interactions and how such an interaction affects complement activation/inactivation. In Aim 2, we will determine the role of genetic or acquired deficiency of CFH on the occurrence, progression, and outcome of acquired TTP (with inhibitors) in murine models. In Aim 3, we propose to determine the prevalence of mutations in genes in complement components and regulators in patients with acquired TTP patients with inhibitors. We pursue the hypothesis that by inhibiting complement activation with anti-complement therapy either alone or in combination with rADAMTS13 one can better prevent the onset and progression of the disease pathology or accelerate its recovery. The results of the proposed study will advance our understanding of the fundamental role of CFH in regulation of VWF function under physiological shear stress, shed new light on the mechanisms of acquired TTP, and provide invaluable tools for testing the efficacy of novel therapeutics.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Pathogenesis of thrombotic microangiopathies
-
批准号:10608740
-
项目类别:
-
资助金额:$51.91万
-
财政年份:2023
-
负责人:X. Long Zheng
-
依托单位:
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic Purpura
-
批准号:10200519
-
项目类别:
-
资助金额:$45.77万
-
财政年份:2019
-
负责人:X. Long Zheng
-
依托单位:
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic Purpura
-
批准号:10372208
-
项目类别:
-
资助金额:$45.77万
-
财政年份:2019
-
负责人:X. Long Zheng
-
依托单位:
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic Purpura
-
批准号:9764787
-
项目类别:
-
资助金额:$44.42万
-
财政年份:2019
-
负责人:X. Long Zheng
-
依托单位:
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic Purpura
-
批准号:10231274
-
项目类别:
-
资助金额:$45.77万
-
财政年份:2019
-
负责人:X. Long Zheng
-
依托单位:
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic Purpura
-
批准号:8504051
-
项目类别:
-
资助金额:$40.92万
-
财政年份:2013
-
负责人:X. Long Zheng
-
依托单位:
Novel Therapeutics for Acquired Thrombotic Thrombocytopenic Purpura
-
批准号:8669155
-
项目类别:
-
资助金额:$41.45万
-
财政年份:2013
-
负责人:X. Long Zheng
-
依托单位:
Cofactor-Dependent Regulation of ADAMTS13 Function
-
批准号:7663368
-
项目类别:
-
资助金额:$36.28万
-
财政年份:2009
-
负责人:X. Long Zheng
-
依托单位:
Structure and Function of ADAMTS13 Metalloprotease
-
批准号:6988488
-
项目类别:
-
资助金额:$32.42万
-
财政年份:2004
-
负责人:X. Long Zheng
-
依托单位:
Structure and Function of ADAMTS13 Metalloprotease
-
批准号:7540945
-
项目类别:
-
资助金额:$31.48万
-
财政年份:2004
-
负责人:X. Long Zheng
-
依托单位:
Structure and Function of ADAMTS13 Metalloprotease
-
批准号:7152582
-
项目类别:
-
资助金额:$31.48万
-
财政年份:2004
-
负责人:X. Long Zheng
-
依托单位:
Structure and Function of ADAMTS13 Metalloprotease
-
批准号:7340524
-
项目类别:
-
资助金额:$31.48万
-
财政年份:2004
-
负责人:X. Long Zheng
-
依托单位:
Structure and Function of ADAMTS13 Metalloprotease
-
批准号:6857422
-
项目类别:
-
资助金额:$33.2万
-
财政年份:2004
-
负责人:X. Long Zheng
-
依托单位:
Cofactor-Dependent Regulation of ADAMTS13 Function
-
批准号:8378088
-
项目类别:
-
资助金额:$36.28万
-
财政年份:--
-
负责人:X. Long Zheng
-
依托单位:
Cofactor-Dependent Regulation of ADAMTS13 Function
-
批准号:8069919
-
项目类别:
-
资助金额:$36.28万
-
财政年份:--
-
负责人:X. Long Zheng
-
依托单位:
Cofactor-Dependent Regulation of ADAMTS13 Function
-
批准号:8450264
-
项目类别:
-
资助金额:$34.54万
-
财政年份:--
-
负责人:X. Long Zheng
-
依托单位:
Cofactor-Dependent Regulation of ADAMTS13 Function
-
批准号:8257876
-
项目类别:
-
资助金额:$36.28万
-
财政年份:--
-
负责人:X. Long Zheng
-
依托单位:
海外基金