SOD3 regulation of redox sensitive signaling in pulmonary vascular diseases
SOD3 对肺血管疾病中氧化还原敏感信号的调节
基本信息
- 批准号:10610425
- 负责人:
- 金额:$ 57.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AgeAnimal ModelAwardBindingBiologyBlood VesselsCD44 geneCell CommunicationCellsDevelopmentDiseaseElectron Spin Resonance SpectroscopyExtracellular MatrixFibroblastsFibrosisFoundationsFundingFutureGene ExpressionGenetic PolymorphismGrowthHalf-LifeHomeostasisHumanHyaluronanIn VitroIndividualInflammasomeInflammationKnock-inKnowledgeLocationLungMacrophageMetabolismMissionModificationMouse StrainsMusNatural ImmunityOxidation-ReductionPathogenesisPathologicPrecision Medicine InitiativePredispositionPropertyPulmonary CirculationPulmonary HypertensionRegulationResearchResearch InfrastructureResearch Project GrantsResource SharingSeriesSeveritiesSignal PathwaySignal TransductionSuperoxide DismutaseTestingTransforming Growth Factor betaTranslatingTranslationsVascular remodelingWorkantioxidant enzymedesignenzyme activityepigenetic regulationexperimental studyextracellularimprovedin vivoindividual variationinsightmitochondrial dysfunctionnew therapeutic targetnovel therapeutic interventionprogramspulmonary vascular disorderreceptorresponsetool
项目摘要
The overall mission of this research program is to determine how the antioxidant enzyme, extracellular
superoxide dismutase (EC-SOD or SOD3) regulates redox-sensitive signaling pathways responsible for
inflammation and fibrosis in pulmonary vascular diseases across the age span, and harness this knowledge to
design new and precise therapies. The different research projects are based on three complementary themes.
Theme 1 interrogates the regulation of SOD3 expression, activity and distribution in the healthy and diseased
pulmonary circulation in the mature and immature lung. These studies would include in vitro, and in vivo
studies using animal models, as well as activity translating the work through new human studies. They will
address the multiple levels of SOD3 regulation, including genetic polymorphisms, epigenetic regulation, or
other post-translation SOD3 modifications, that can influence gene expression, enzyme activity, half-life and
localization. Theme 2 evaluates how changes in SOD3 activity or binding properties impact redox sensitive
signaling pathways that are responsible for the development of pulmonary vascular disease, in particular,
inflammation and subsequent vascular remodeling and fibrosis. These experiments utilize a unique series of
SOD3 mouse strains, including a mouse with knock-in of a known human SOD3 polymorphism, to interrogate
how individual changes in SOD3 location or content can influence disease pathogenesis and severity. Based
on the unique extracellular localization of SOD3, studies will test the effects of insufficient SOD3 on matrix
integrity, matrix-cell interactions, cell-cell interactions and communication between extracellular signals and
intracellular cellular responses. Ongoing studies are testing how the loss of vascular SOD3 increases the
susceptibility of two key redox-sensitive targets localized to the extracellular matrix (ECM): activation of latent
TGF-β, which enhances PASMC and fibroblast growth, inflammation and synthetic function, or oxidative
fragmentation of hyaluronan, which binds to macrophage CD44 receptors and activates the NLRP3
inflammasome. Future planned studies will test how altered SOD3 impacts the redox landscape to modulate
innate immunity, cellular metabolism and mitochondrial dysfunction responsible for vascular fibrosis in PH.
Theme 3 translates the findings into new therapeutic strategies to replenish deficient SOD3 to restore redox
homeostasis. This framework is supported by a new initiative, funded by a Dean's Strategic Infrastructure
Research Committee Award for the purchase of an electron paramagnetic resonance spectrometer, to develop
a collaborative and interdisciplinary UCD Redox Biology Shared Resource Facility to advance the study of
Redox Biology. These studies collectively will provide new insight relevant to the mission of the Precision
Medicine Initiative, as they will uncover how individual variables that influence SOD3 impact the development
of inflammation and fibrosis in pulmonary hypertension.
这项研究计划的总体任务是确定细胞外的抗氧化酶是如何
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Eva S. Nozik其他文献
Nbeal2 knockout mice are not protected against hypoxia-induced pulmonary vascular remodeling and pulmonary hypertension
Nbeal2基因敲除小鼠对缺氧诱导的肺血管重构和肺动脉高压没有保护作用
- DOI:
10.1182/bloodadvances.2024013880 - 发表时间:
2025-04-08 - 期刊:
- 影响因子:7.100
- 作者:
Janelle N. Posey;Mariah Jordan;Caitlin V. Lewis;Christina Sul;Evgenia Dobrinskikh;Delaney Swindle;Frederik Denorme;David Irwin;Jorge Di Paola;Kurt Stenmark;Eva S. Nozik;Cassidy Delaney - 通讯作者:
Cassidy Delaney
Eva S. Nozik的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Eva S. Nozik', 18)}}的其他基金
R35 Administrative Supplements to Recognize Excellencein Diversity, Equity, Inclusion, and Accessibility (DEIA)Mentorship
R35 表彰多元化、公平、包容性和可及性 (DEIA) 指导方面卓越表现的行政补充
- 批准号:
10630461 - 财政年份:2022
- 资助金额:
$ 57.14万 - 项目类别:
Collaborative Pediatric Critical Care Research Network - Clinical Site
儿科重症监护协作研究网络 - 临床网站
- 批准号:
10470946 - 财政年份:2021
- 资助金额:
$ 57.14万 - 项目类别:
Collaborative Pediatric Critical Care Research Network - Clinical Site
儿科重症监护协作研究网络 - 临床网站
- 批准号:
10667490 - 财政年份:2021
- 资助金额:
$ 57.14万 - 项目类别:
SOD3 regulation of redox sensitive signaling in pulmonary vascular diseases
SOD3 对肺血管疾病中氧化还原敏感信号的调节
- 批准号:
10847902 - 财政年份:2018
- 资助金额:
$ 57.14万 - 项目类别:
SOD3 regulation of redox sensitive signaling in pulmonary vascular diseases
SOD3 对肺血管疾病中氧化还原敏感信号的调节
- 批准号:
10433989 - 财政年份:2018
- 资助金额:
$ 57.14万 - 项目类别:
SOD3 regulation of redox sensitive signaling in pulmonary vascular diseases
SOD3 对肺血管疾病中氧化还原敏感信号的调节
- 批准号:
10237868 - 财政年份:2018
- 资助金额:
$ 57.14万 - 项目类别:
DNA methylation of extracellular superoxide dismutase in pulmonary hypertension
肺动脉高压细胞外超氧化物歧化酶 DNA 甲基化
- 批准号:
8335465 - 财政年份:2011
- 资助金额:
$ 57.14万 - 项目类别:
Regulation of extracellular superoxide dismutase in human pulmonary arterial hype
细胞外超氧化物歧化酶在人肺动脉高压中的调节
- 批准号:
8210797 - 财政年份:2011
- 资助金额:
$ 57.14万 - 项目类别:
Extracellular superoxide induces Egr-1 in the hypoxic pulmonary artery
细胞外超氧化物在缺氧肺动脉中诱导 Egr-1
- 批准号:
7841072 - 财政年份:2009
- 资助金额:
$ 57.14万 - 项目类别:
Extracellular superoxide induces Egr-1 in the hypoxic pulmonary artery
细胞外超氧化物在缺氧肺动脉中诱导 Egr-1
- 批准号:
8197441 - 财政年份:2007
- 资助金额:
$ 57.14万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 57.14万 - 项目类别:
Grant-in-Aid for Early-Career Scientists