The role of chorioamnionitis-induced perinatal alterations of Heme-oxygenase-1 (HO-1) pathway on neuroinflammation and neonatal white matter injury
绒毛膜羊膜炎引起的围产期血红素加氧酶-1 (HO-1) 通路改变对神经炎症和新生儿白质损伤的作用
基本信息
- 批准号:10524936
- 负责人:
- 金额:$ 17.17万
- 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:2022-09-15 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdultAnti-Inflammatory AgentsApoptoticBiological Response ModifiersBiologyBlood CirculationBrainBrain InjuriesCell DeathCellsCerebral PalsyCerebrumCognitive deficitsComplexDataDevelopmentDevelopment PlansDiagnosticDiseaseDoctor of PhilosophyEnsureEnvironmentEnzymesExposure toFoundationsFutureGene ProteinsGrantHistopathologyHomeostasisImmuneImmune responseImpaired cognitionInflammatoryInvestigationIronKnowledgeLearningMeasuresMediatingMentorsMentorshipMicrogliaModelingMolecularMononuclearMyelogenousMyeloid CellsNeonatalNeuraxisNeurodevelopmental ImpairmentNeuroimmuneNeurosciencesNeurosciences ResearchOligodendrogliaOxidative StressPathway interactionsPatternPediatricsPerinatalPerinatal Brain InjuryPeripheralPhenotypePhysiciansPremature BirthPremature InfantProgram DevelopmentRattusReactive Oxygen SpeciesRegulationResearchResearch PersonnelRoleScientistSecondary toSignal TransductionTFRC geneTechnical ExpertiseTechniquesTestingTherapeutic InterventionTimeTrainingTraining ProgramsUniversitiesUp-Regulationbasebehavioral studycareercareer developmentchemokinecytokineexecutive functionheme oxygenase-1high riskimmunoregulationinnovationinsightintraamniotic infectionmacrophagemedical schoolsmonocyteneonatenervous system developmentneuroimmunologyneuroinflammationnovelnovel markerpreterm newbornprofessorresponserestorationskillsspatiotemporaltargeted treatmentwhite matterwhite matter injury
项目摘要
PROJECT SUMMARY/ABSTRACT:
The proposal in this application outlines a five-year training program for the development of a career as a
physician-scientist in neonatal neuroimmunology. Candidate, Dr. Maide Ozen, is an Early Stage Investigator and
an Assistant Professor of Pediatrics at the Johns Hopkins University School of Medicine. The proposed research
will be carried out under the primary mentorship of Dr. Lauren L. Jantzie, PhD, an expert leader in translational
investigations in perinatal brain injury. Candidate’ s co-mentors are Dr. Shenandoah Robinson, M.D. an expert
in oligodendrocyte biology and Dr. Frances J. Northington, M.D. an esteemed Neonatologist and a leader in cell
death pathways in the brain. Specific training objectives of this K08 proposal are: develop Dr. Ozen’s scientific
and professional skills in 1) advanced neuroimmunology and neuroscience techniques, 2) gene-protein
interactions specific to Heme oxygenase-1 (HO-1) to lay the foundation for a future R01 application.
Neuroscience research at JHU is exceptionally strong. Dr. Ozen and her mentoring committee have developed
a focused approach to achieve these objectives. The experiential research environment, intellectual guidance
and carefully selected didactic courses, each matched to a specific aim in this proposal, will ensure rigorous
training in neuroimmunology for achieving independence.
White matter injury (WMI) is the most common form of brain injury in preterm neonates. Key focus of
candidates proposed project is interrogating HO-1 pathway, for the first time, in perinatal WMI. HO-1 is an anti-
inflammatory, anti-apoptotic and cytoprotective enzyme with essential roles in immune regulation and is
expressed in mononuclear cells, microglia and oligodendrocytes. The candidate is the first to show that
chorioamnionitis-induced perinatal alterations of HO-1 pathway in the developing rat brain correlate with
neuroinflammation. Therefore, utilizing a validated CHORIO model of Cerebral Palsy, the candidate will first
determine how CHORIO alters HO-1 pathway in WMI; second, determine if intracellular HO-1 expression in
peripheral mononuclear cells and brain microglia differentially contribute to WMI in CHORIO; third, determine if
modulation of HO-1 pathway will protect from WMI in CHORIO. Completion of the targeted career development
program and research proposed in this proposal will allow the candidate to learn new technical skills and gain
neuroscience expertise to excel as a physician-scientist in neuroimmunology and advance the field of HO-1
biology to perinatal brain injury. Rigorous inquiry in regulation of HO-1 pathway in CHORIO could provide
discovery of novel biomarkers and targeted therapeutic strategies for perinatal immune-mediated WMI.
项目概要/摘要:
本申请中的提案概述了一个为期五年的职业发展培训计划
Maide Ozen 博士是新生儿神经免疫学领域的临床科学家,也是一名早期研究员。
约翰·霍普金斯大学医学院儿科助理教授拟议的研究。
将在转化领域专家领导者 Lauren L. Jantzie 博士的主要指导下进行
围产期脑损伤研究的共同导师是医学博士 Shenandoah Robinson 博士。
Frances J. Northington 博士是少突胶质细胞生物学博士,医学博士,一位受人尊敬的新生儿学家和细胞领域的领导者
K08 提案的具体训练目标是:发展 Ozen 博士的科学知识。
以及 1) 先进神经免疫学和神经科学技术,2) 基因-蛋白质方面的专业技能
与血红素加氧酶-1 (HO-1) 特异性的相互作用,为未来 R01 应用奠定基础。
约翰·奥森博士和她的指导委员会的神经科学研究非常强大。
实现这些目标的重点方法。
精心挑选的教学课程,每门课程都与本提案中的具体目标相匹配,将确保严格的
神经免疫学培训以实现独立。
白质损伤(WMI)是早产儿最常见的脑损伤形式。
候选人提出的项目是首次探讨 HO-1 通路在围产期 WMI 中的作用。
炎症、抗凋亡和细胞保护酶,在免疫调节中发挥重要作用,
该候选者是第一个证明这一点的人。
绒毛膜羊膜炎引起的发育中大鼠大脑中 HO-1 通路的围产期改变与
因此,利用经过验证的脑瘫 CHORIO 模型,候选人将首先
确定 CHORIO 如何改变 WMI 中的 HO-1 通路;其次,确定细胞内 HO-1 表达是否在
外周单核细胞和脑小胶质细胞对 CHORIO 中 WMI 的贡献存在差异;第三,确定是否存在差异;
HO-1 通路的调节将保护 CHORIO 免受 WMI 的影响,完成目标职业发展。
本提案中提出的计划和研究将使候选人能够学习新的技术技能并获得
神经科学专业知识,成为神经免疫学领域的医师科学家并推动 HO-1 领域的发展
对 CHORIO 中 HO-1 通路调节的严格研究可以为围产期脑损伤提供生物学依据。
发现围产期免疫介导的 WMI 的新型生物标志物和靶向治疗策略。
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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Maide Ozen其他文献
Maide Ozen的其他文献
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{{ truncateString('Maide Ozen', 18)}}的其他基金
The role of chorioamnionitis-induced perinatal alterations of Heme-oxygenase-1 (HO-1) pathway on neuroinflammation and neonatal white matter injury
绒毛膜羊膜炎引起的围产期血红素加氧酶-1 (HO-1) 通路改变对神经炎症和新生儿白质损伤的作用
- 批准号:
10705202 - 财政年份:2022
- 资助金额:
$ 17.17万 - 项目类别:
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