The Role of RNA Binding Motif 5 in Traumatic Brain Injury
RNA 结合基序 5 在创伤性脑损伤中的作用
基本信息
- 批准号:10016850
- 负责人:
- 金额:$ 32.7万
- 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:2018-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalApoptosisAutophagocytosisAxonBindingBrainCardiovascular DiseasesCaspaseCause of DeathCell DeathCellsCerebral IschemiaCessation of lifeCognitiveDataDiseaseDown-RegulationEnterobacteria phage P1 Cre recombinaseEtiologyEventExonsFoundationsFundingFutureGene DeletionGene ExpressionGenesHippocampus (Brain)HistologicHumanImpairmentIn VitroInjuryKnock-outKnockout MiceKnowledgeLearningLocationMalignant NeoplasmsMeasuresMechanicsMediatingMedicalMemoryMessenger RNAModelingMolecularMonomeric GTP-Binding ProteinsMotorMultiple TraumaMusNervous System TraumaNeurologicNeuronal InjuryNeuronsNormal CellNuclearOrganOutcomePathologicPlayPredispositionProteinsPublishingRBM5 geneRNA BindingRNA SplicingRNA analysisRNA-Binding ProteinsRattusReportingResearchResearch ActivityResource SharingResourcesRoleSignal TransductionSpinal CordSpinal cord injuryStaurosporineStretchingStructureSubfamily lentivirinaeTBI treatmentTestingTimeTissuesToxic effectTraumaTraumatic Brain InjuryUnited States National Institutes of HealthUp-RegulationVertebral columnWorkbehavioral outcomecancer cellcell growthcentral nervous system injuryclinically relevantcognitive functioncontrolled cortical impactdata resourcedisabilitydrug developmentexperimental studygene functionimprovedin vitro testingin vivoin vivo evaluationinnovationknock-downmutantnervous system disorderneurological recoveryneuron lossneuropathologyneuroprotectionneurotoxicneurotoxicitynext generation sequencingnovelnovel therapeutic interventionnovel therapeuticsoverexpressionpreventrepairedsmall moleculetooltranscriptometreatment strategy
项目摘要
ABSTRACT
Traumatic brain injury (TBI) is a leading cause of death and disability in the young. Treatments are
desperately needed to prevent cell death, repair neuronal connectivity, and improve cognitive outcomes after a
TBI. This project will test if gene deletion of RNA binding motif 5 (RBM5) in mice improves molecular and
histological readouts and behavioral outcomes after a controlled cortical impact (CCI) injury.
RNA binding proteins (RBPs) regulate all aspects of mRNA (e.g. RNA splicing, gene expression,
stability, and cellular localization). In recent years a number of RBPs have been associated with the etiology of
disorders ranging from cancer, to cardiovascular and neurological disease. RBM5 is a pro-death RBP. The
mechanisms by which RBM5 induces cell death involves upregulation of pro-death genes and also via the
modulation of mRNA splicing ,which gives rise to toxic proteins with increased potency. Forced overexpression
of RBM5 in cancer cells causes apoptosis, autophagy, and impedes cell growth. Very little is known about the
function(s) of RBM5 in non-cancerous (i.e. normal) cells and tissues. Germane to the CNS, we showed that
RBM5 levels increase after a TBI in mice. Independent of our work, RBM5 levels also reportedly increase after
a traumatic spinal cord injury. It remains to be elucidated if RBM5 activates cell death in primary CNS cells (as
it does in cancer). Our new preliminary data show that RBM5 overexpression in primary rat cortical neurons
increases their susceptibility to a subsequent mechanical stretch-injury. This new finding is in line with our
hypothesis that (1) RBM5 inhibition is a promising new therapeutic strategy for the treatment of CNS injury,
and (2) suggests that RBM5 dysregulation may mediate pathological changes in gene expression which has
been observed to occur after a TBI.
In this project we will definitely test if RBM5 inhibition is neuroprotective in vivo. Novel conditional
RBM5 KO mice will be subjected to a CCI induced injury. Neuropathology in WT versus KOs will be examined
1-21d post-injury. Also, learning and memory function will be examined 14-21d post-injury. Additionally we will
analyze changes in global gene expression/splicing in primary cortical neurons after a mechanical stretch-
injury, and also in which RBM5 levels are manipulated (i.e. by lentivirus mediated knockdown vs.
overexpression). This study represents the most in-depth, largest, and only analysis of RBM5 gene function in
brain which has been done to date.
摘要
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 }}
TRAVIS C JACKSON其他文献
TRAVIS C JACKSON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('TRAVIS C JACKSON', 18)}}的其他基金
The Role of RNA Binding Motif 5 in Traumatic Brain Injury
RNA 结合基序 5 在创伤性脑损伤中的作用
- 批准号:
10200911 - 财政年份:2018
- 资助金额:
$ 32.7万 - 项目类别:
The Role of RNA Binding Motif 5 in Traumatic Brain Injury
RNA 结合基序 5 在创伤性脑损伤中的作用
- 批准号:
9494899 - 财政年份:2018
- 资助金额:
$ 32.7万 - 项目类别:
The Role of RNA Binding Motif 5 in Traumatic Brain Injury
RNA 结合基序 5 在创伤性脑损伤中的作用
- 批准号:
10445318 - 财政年份:2018
- 资助金额:
$ 32.7万 - 项目类别:
FGF21 Activates RBM3 and is a Novel Drug to Revolutionize Temperature Management
FGF21激活RBM3,是彻底改变温度管理的新药
- 批准号:
9314031 - 财政年份:2017
- 资助金额:
$ 32.7万 - 项目类别:
The mRNA splicing factor RBM5: A new therapeutic target for TBI
mRNA剪接因子RBM5:TBI的新治疗靶点
- 批准号:
8845278 - 财政年份:2014
- 资助金额:
$ 32.7万 - 项目类别:
The mRNA splicing factor RBM5: A new therapeutic target for TBI
mRNA剪接因子RBM5:TBI的新治疗靶点
- 批准号:
8749903 - 财政年份:2014
- 资助金额:
$ 32.7万 - 项目类别:
相似国自然基金
Epac1/2通过蛋白酶体调控中性粒细胞NETosis和Apoptosis在急性肺损伤中的作用研究
- 批准号:LBY21H010001
- 批准年份:2020
- 资助金额:0.0 万元
- 项目类别:省市级项目
基于Apoptosis/Ferroptosis双重激活效应的天然产物AlbiziabiosideA的抗肿瘤作用机制研究及其结构改造
- 批准号:81703335
- 批准年份:2017
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
双肝移植后Apoptosis和pyroptosis在移植物萎缩差异中的作用和供受者免疫微环境变化研究
- 批准号:81670594
- 批准年份:2016
- 资助金额:58.0 万元
- 项目类别:面上项目
Serp-2 调控apoptosis和pyroptosis 对肝脏缺血再灌注损伤的保护作用研究
- 批准号:81470791
- 批准年份:2014
- 资助金额:73.0 万元
- 项目类别:面上项目
Apoptosis signal-regulating kinase 1是七氟烷抑制小胶质细胞活化的关键分子靶点?
- 批准号:81301123
- 批准年份:2013
- 资助金额:23.0 万元
- 项目类别:青年科学基金项目
APO-miR(multi-targeting apoptosis-regulatory miRNA)在前列腺癌中的表达和作用
- 批准号:81101529
- 批准年份:2011
- 资助金额:22.0 万元
- 项目类别:青年科学基金项目
放疗与细胞程序性死亡(APOPTOSIS)相关性及其应用研究
- 批准号:39500043
- 批准年份:1995
- 资助金额:9.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Milk fat globule-EGF factor 8 and hepatocyte apoptosis-induced liver wound healing response
乳脂肪球-EGF因子8与肝细胞凋亡诱导的肝脏创面愈合反应
- 批准号:
10585802 - 财政年份:2023
- 资助金额:
$ 32.7万 - 项目类别:
Development of an apoptosis biosensor for monitoring of breast cancer
开发用于监测乳腺癌的细胞凋亡生物传感器
- 批准号:
10719415 - 财政年份:2023
- 资助金额:
$ 32.7万 - 项目类别:
Interrogating the Fgl2-FcγRIIB axis on CD8+ T cells: A novel mechanism mediating apoptosis of tumor-specific memory CD8+ T cells
询问 CD8 T 细胞上的 Fgl2-FcγRIIB 轴:介导肿瘤特异性记忆 CD8 T 细胞凋亡的新机制
- 批准号:
10605856 - 财政年份:2023
- 资助金额:
$ 32.7万 - 项目类别:
Novel targeted therapy for FGFR inhibitor-resistant urothelial cancer and apoptosis based therapy for urothelial cancer
FGFR抑制剂耐药性尿路上皮癌的新型靶向治疗和基于细胞凋亡的尿路上皮癌治疗
- 批准号:
23K08773 - 财政年份:2023
- 资助金额:
$ 32.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanistic analysis of apoptosis induction by HDAC inhibitors in head and neck cancer
HDAC抑制剂诱导头颈癌凋亡的机制分析
- 批准号:
23K15866 - 财政年份:2023
- 资助金额:
$ 32.7万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Interrogating the Fgl2-FcgRIIB axis: A novel mechanism mediating apoptosis of tumor-specific memory CD8+ T cells
探究 Fgl2-FcgRIIB 轴:介导肿瘤特异性记忆 CD8 T 细胞凋亡的新机制
- 批准号:
10743485 - 财政年份:2023
- 资助金额:
$ 32.7万 - 项目类别:
Investigating the role of apoptosis-resistance and the tumor environment on development and maintenance of sacrococcygeal teratomas
研究细胞凋亡抗性和肿瘤环境对骶尾部畸胎瘤发生和维持的作用
- 批准号:
10749797 - 财政年份:2023
- 资助金额:
$ 32.7万 - 项目类别:
The effects of glucose on immune cell apoptosis and mitochondrial membrane potential and the analysis of its mechanism by which glucose might modulate the immune functions.
葡萄糖对免疫细胞凋亡和线粒体膜电位的影响及其调节免疫功能的机制分析。
- 批准号:
22K09076 - 财政年份:2022
- 资助金额:
$ 32.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
XAF1 IN P53 SIGNALING, APOPTOSIS AND TUMOR SUPPRESSION
P53 信号传导、细胞凋亡和肿瘤抑制中的 XAF1
- 批准号:
10583516 - 财政年份:2022
- 资助金额:
$ 32.7万 - 项目类别:
Role of Thioredoxin system in regulation of autophagy-apoptosis cross talk in neurons: Uncovering Novel Molecular Interactions.
硫氧还蛋白系统在神经元自噬-凋亡串扰调节中的作用:揭示新的分子相互作用。
- 批准号:
RGPIN-2019-05371 - 财政年份:2022
- 资助金额:
$ 32.7万 - 项目类别:
Discovery Grants Program - Individual