The protective role of fibroblast growth factor signaling in hypoxia-induced pulmonary hypertension
成纤维细胞生长因子信号传导在缺氧诱导的肺动脉高压中的保护作用
基本信息
- 批准号:10506740
- 负责人:
- 金额:$ 16.51万
- 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:Adenovirus VectorAdenovirusesAdultAffectBiologyBlood VesselsBronchopulmonary DysplasiaCardiopulmonaryCell CommunicationCellsCessation of lifeChronic Obstructive Pulmonary DiseaseClassificationCollaborationsDataDevelopmentDevelopment PlansDiseaseDisease modelDistalEndothelial CellsEndotheliumEngineeringExposure toExtramural ActivitiesFGFR1 geneFellowshipFibroblast Growth FactorFibroblast Growth Factor ReceptorsGene DeliveryGeneticGenetic ModelsGoalsHypoxemiaHypoxiaInnovative TherapyKnockout MiceKnowledgeLaboratoriesLigandsLungLung diseasesMentorshipMesenchymalMethodsMissionModelingMolecularMorbidity - disease rateMusMuscleNational Heart, Lung, and Blood InstituteOutcomePathogenesisPathogenicityPathologicPathway interactionsPatientsPediatric cardiologyPhenotypePhysiciansPhysiologicalPre-Clinical ModelPremature InfantPrincipal InvestigatorProductionPulmonary HypertensionPulmonary artery structureRegulationResearchResearch PersonnelResourcesRoleScientistSeveritiesSignal PathwaySignal TransductionSmooth MuscleSmooth Muscle MyocytesStressStructure of parenchyma of lungTechniquesTherapeuticTherapeutic InterventionTrainingTraining ProgramsTransforming Growth Factor betaUnited States National Institutes of HealthUniversitiesVascular Endothelial CellVascular EndotheliumVascular Smooth MuscleVascular remodelingWashingtonWorkadenovirus mediated deliveryangiogenesisauthoritycareer developmentcollaborative environmentconditional knockoutearly detection biomarkersexperiencegain of functiongene therapyhemodynamicshypoxia-induced pulmonary hypertensionimprovedimproved outcomein vivoloss of functionmedical schoolsmortalitymouse geneticsnew therapeutic targetprematurepreventpulmonary vascular disorderpulmonary vascular remodelingresponseskillstherapeutic targettissue injurytooltranslational approach
项目摘要
Project Summary
This K08 proposal will expedite the principal investigator’s progress towards his goal of becoming an
independent physician-scientist focused on increasing our understanding of pathogenic mechanisms of
pulmonary hypertension (PH) and developing innovative therapies to improve outcomes.
Candidate: Dr. Kel Vin Woo is a physician-scientist at Washington University School of Medicine (WUSM).
He completed a fellowship in Pediatric Cardiology and is developing expertise at the intersection of Fibroblast
Growth Factors (FGF) signaling and vascular biology under the mentorship of Dr. David Ornitz, a world authority
on FGF biology. Under Dr. Ornitz’s mentorship, the PI investigated how endothelial FGF signaling modulates
hypoxia-induced PH by mitigating endothelial-to-mesenchymal transition. He will leverage the skills gained
during his fellowship to further analyze FGF signaling in vascular smooth muscle cells and use adenovirus-
delivered endothelial FGF as a potential method of regulating vascular remodeling.
Career Development Plan: Dr. Woo will pursue this line of research with primary mentorship from Dr. Ornitz
and co-mentorship from Dr. Curiel (an expert in adenovirus vectorology). Additionally, a team of intramural and
extramural advisors include experts in PH, and vascular and pulmonary biology, and all have considerable
experience in nurturing independent investigators. WUSM provides a highly interactive environment with
excellent facilities, resources and opportunities. This 5-year plan builds on the PI’s prior experience and further
enriches his training, providing him with the tools needed for independence. It includes the following objectives:
(1) Master techniques in advanced mouse hemodynamic phenotyping; (2) Become proficient with adenovirus
engineering to improve PH outcomes using preclinical models of hypoxia-induced vascular remodeling; (3)
Disseminate research findings in diverse venues and actively establish productive collaborations.
Research Plan: The overall hypothesis of the proposal is that FGF signaling in lung endothelial and vascular
smooth muscle cells protects against hypoxia-induced PH. Specific Aim 1 will investigate how smooth muscle
cell FGF prevents pulmonary vascular remodeling. Aim 2 will interrogate how endothelial targeted adenovirus-
delivered FGF reduces hypoxia-induced vascular remodeling and PH severity. Upon completion of the proposed
research, Dr. Woo will be proficient in: (1) modulating intracellular pathways important for endothelial and smooth
muscle cell remodeling; (2) analyzing newly developed conditional knockout mice to ascertain the hemodynamic
effects on the lungs; and (3) developing approaches for gene delivery to lung endothelium as a potential therapy
for pulmonary vascular disease. These acquired skills will be readily applicable to other forms pulmonary
vascular disease and endothelial-smooth muscle interactions in vascular remodeling. Upon completion of the
proposed training, Dr. Woo will have acquired the necessary expertise to become an independent investigator
focused on reducing the burden of pulmonary diseases, in alignment with the NHLBI mission.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Kel Vin WOO', 18)}}的其他基金
The protective role of fibroblast growth factor signaling in hypoxia-induced pulmonary hypertension
成纤维细胞生长因子信号传导在缺氧诱导的肺动脉高压中的保护作用
- 批准号:
10707357 - 财政年份:2022
- 资助金额:
$ 16.51万 - 项目类别:
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