Mechanistic basis of sexual dimorphism in antigen-independent IgG1 angiogenesis regulation
Mechanistic basis of sexual dimorphism in antigen-independent IgG1 angiogenesis regulation
批准号:
10660051
负责人:
Bradley David Gelfand
金额:
$68.99万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-04-01 至 2027-02-28
关键词:
AffinityAlzheimer&aposs DiseaseAngiogenesis InhibitorsAnimal ModelAnimalsAntibodiesAntigensBedsBiologicalBlood CellsBlood VesselsBone MarrowCardiovascular systemCellsChemotaxisChoroidal NeovascularizationComplementCoronary ArteriosclerosisDataDevelopmentDiabetic RetinopathyDiseaseEstradiolEstrogensEventExhibitsExudative age-related macular degenerationFc domainFemaleFour Core GenotypesGenesGeneticGleanGoalsGonadal HormonesGrowthGuidelinesHeart failureHindlimbHormonalHormonesHumanIgG1ImmuneInterventionIschemiaKnock-outKnowledgeMacrophageMacular degenerationMalignant NeoplasmsMediatingMediatorModelingMorbidity - disease rateMusMyocardial IschemiaNaturePathologic NeovascularizationPathway interactionsPeripheral arterial diseasePhysiologicalPlasmaPloidiesPredispositionPrevalenceProcessRegulationRegulator GenesRisk FactorsRoleSeveritiesSeverity of illnessSex BiasSex ChromosomesSex DifferencesSignal TransductionSpecimenStrokeSystemTestingTestosteroneTherapeuticTissuesUnited States National Institutes of HealthVEGFA geneY Chromosomeangiogenesisantigen bindingchromosome Y lossdimorphismgain of functiongenotypic sexhelicasehuman maleimproved outcomeinhibiting antibodyinsightknock-downloss of functionmalemortalitymosaic lossneovascularizationnovelpersonalized therapeuticpreventreceptorresponsesegregationsexsexual dimorphism
中文摘要
项目摘要/总结
英文摘要
PROJECT ABSTRACT/SUMMARY
Diseases of excess, aberrant, or insufficient angiogenesis are responsible for a large portion of the world's
morbidity and mortality. Conditions such as peripheral artery disease, macular degeneration, coronary artery
disease, stroke, and heart failure exhibit sexual dimorphism in risk factors, prevalence, severity, or optimal
interventions. Despite widespread appreciation of these differences, the mechanisms by which sex influences
vascular conditions are incompletely understood. For example, the role of sex chromosomal complement in
angiogenic processes is ill defined. New evidence suggests that the process by which IgG1 antibodies regulate
angiogenesis in an antigen-independent manner (which we term “antibody-dependent cell-mediated
angioinhibition” or ADCAI) is strongly sexually dimorphic, with males exhibiting far greater ADCAI compared to
females. Supported by robust preliminary data, the overall hypothesis of this project is ADCAI dimorphism arises
due to expression of the Y chromosome-encoded gene DDX3Y. We will test this hypothesis in three specific
aims. 1) We will establish the precise roles of sex-biasing factors (sex chromosome complement and gonadal
secretions) in ADCAI sexual dimorphism. 2) We will determine the function of the Y chromosome-encoded
DDX3Y as a novel ADCAI regulatory gene. 3) We will quantify the sex effect on ADCAI in human cells and
specimens. Collectively, these thematically related, but independent aims will establish new foundational and
translationally relevant knowledge about the mediators and consequences of ADCAI. These studies may thereby
open new interventional avenues to modulate angiogenesis in a personalized, sex-specific manner for diverse
therapeutic applications.
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会议论文
DICER1 deficiency in aberrant chorioretinal neovascularization - Administrative Supplement OKT Request
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批准号:10647413
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项目类别:
-
资助金额:$6.02万
-
财政年份:2021
-
负责人:Bradley David Gelfand
-
依托单位:
DICER1 deficiency in aberrant chorioretinal neovascularization
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批准号:10407583
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项目类别:
-
资助金额:$49.5万
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财政年份:2021
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负责人:Bradley David Gelfand
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依托单位:
DICER1 deficiency in aberrant chorioretinal neovascularization
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批准号:10624267
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项目类别:
-
资助金额:$51.04万
-
财政年份:2021
-
负责人:Bradley David Gelfand
-
依托单位:
DICER1 deficiency in aberrant chorioretinal neovascularization
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批准号:10183845
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项目类别:
-
资助金额:$52.57万
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财政年份:2021
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负责人:Bradley David Gelfand
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依托单位: