Choline kinase: a novel target for rheumatoid arthritis
胆碱激酶:类风湿性关节炎的新靶点
基本信息
- 批准号:8566419
- 负责人:
- 金额:$ 13.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-01 至 2018-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAggressive behaviorArthritisAwardBehaviorBiological MarkersBiologyCaliforniaCartilageCellsCellular biologyChemicalsCholineCholine KinaseChronicClinicalClinical TrialsComplementComplexDataDegenerative polyarthritisDevelopmentDevelopment PlansDiagnosticDiseaseDoctor of PhilosophyEnvironmentEnzyme-Linked Immunosorbent AssayEnzymesEventFellowshipFibroblastsGene ExpressionGenomicsGrowthHealthHumanImmuneImmune systemImmunologyInflammationInflammation MediatorsInflammatoryInformaticsInvadedInvestigationJointsJournalsK/BxN modelKidneyLaboratoriesLeadLiverMagnetic Resonance SpectroscopyMalignant NeoplasmsMatrix MetalloproteinasesMeasuresMediatingMediator of activation proteinMedicalMedicineMentorsMethodsModelingMolecular BiologyMusOrganOsteoarthrosis DeformansPathogenesisPathway interactionsPatientsPatternPharmaceutical PreparationsPharmacotherapyPhenotypePhospholipidsPhosphorylcholinePhosphotransferasesPhysiciansPopulationPrincipal InvestigatorProductionPrognostic MarkerProteomicsRecruitment ActivityRegulationResearchResearch InstituteResearch PersonnelResearch ProposalsRheumatoid ArthritisRheumatologyRoleSamplingScientistSecondary toSerumSignal TransductionSmall Interfering RNASpainStagingSynovial MembraneTechniquesTechnologyTestingTimeTissue SampleTissuesToxic effectToxicologyTrainingTraining ProgramsTranslational ResearchUnited StatesUniversitiesarmarticular cartilagebasecareer developmentclinical phenotypecytokinedesignexperienceimprovedin vivojoint destructionjoint injurykinase inhibitorknock-downloss of functionmetabolomicsmigrationnovelnovel therapeutic interventionpatient oriented researchpost-doctoral trainingpre-clinicalprofessorprogramsresponseskillssystemic autoimmune diseasetherapeutic targettooltumortumorigenesis
项目摘要
DESCRIPTION (provided by applicant): This proposal describes a five year mentored research program in laboratory and clinical based research essential to the development of the principal investigator as an independent investigator. The principal investigator has completed her medical studies, specializing in Rheumatology, and Ph.D. studies in Immunology in Barcelona, Spain. She then moved to San Diego to join Dr. Michael Karin's lab for her postdoctoral training in signal transduction. She is now realizing Rheumatology Fellowship at the University of California at San Diego and will expand upon her research skills through a focused individualized career development plan. The program will provide training in molecular and cell biology of synovial fibroblasts and arthritis models applied to chronic inflammation and rheumatoid arthritis (RA). By the end of her award period, she will also have developed the skill sets required to conduct independent investigation in pre-clinical translational research, and patient-oriented research in the field of Rheumatology. Her studies will also require additional training in proteomics, NMR, and metabolomics that will provide her with important new tools that can be applied to her research as an independent investigator. Dr. Gary S. Firestein is a professor of medicine and dean of translational research institute at UC San Diego and will mentor the principal investigator's scientific development. Dr. Firestein is a recognized leader in
signal transduction and pathogenesis of rheumatoid arthritis and has a strong record of mentoring physician scientists. Dr. Michael Karin is also a recognized leader in signal transduction and inflammation will provide additional guidance as a co-mentor in this filed. Dr. Kavanaugh, as a clinical mentor, will assist with developing novel biomarkers using patient samples. Of note, the principal investigator has no experience in biomarker analysis synovial fibroblast biology, patient-oriented research, and clinical trials and those skills would be essential for transition to an independent investigator. In addition, our collaborators will help wth the use of the technology and informatics for metabolomics studies, with the interpretation of results and how it can be applied to developing new biomarkers. Didactic courses, seminars, journal clubs and 80% protected time for specific training in laboratory techniques in a supportive academic environment in the Department of Medicine at UCSD will complement the training program. The research proposal will focus on the role of choline kinase in chronic inflammation and joint destruction associated with RA. In addition, these studies will determine whether this enzyme is a potential therapeutic target to treat inflammatory disorders. We will also explore the role of this kinase and its downstream products as diagnostic or prognostic biomarker. The proposal builds upon preliminary studies demonstrating a novel function of choline kinase in proliferation and survival of fibroblast-like synoviocytes derived from RA patients. The proposed studies will explore function and regulation of choline kinase in key signaling events, inflammation and joint destruction in RA. In addition, expression, function and regulation of choline kinase will be determined in cells and tissue samples derived from patients with RA. The relationship between the choline kinase metabolites pattern and disease activity as determined by clinical disease measures will be determined
描述(由申请人提供):该提案描述了一项为期五年的实验室和临床研究指导研究计划,这对于主要研究人员作为独立研究人员的发展至关重要。主要研究者已完成她的医学研究,专攻风湿病学,并获得博士学位。在西班牙巴塞罗那攻读免疫学。然后,她搬到圣地亚哥,加入 Michael Karin 博士的实验室,接受信号转导方面的博士后培训。她目前正在加州大学圣地亚哥分校获得风湿病学奖学金,并将通过有针对性的个性化职业发展计划来扩展她的研究技能。该项目将提供滑膜成纤维细胞的分子和细胞生物学以及应用于慢性炎症和类风湿性关节炎(RA)的关节炎模型的培训。在获奖期结束时,她还将掌握在临床前转化研究和风湿病领域以患者为导向的研究中进行独立调查所需的技能。她的研究还需要蛋白质组学、核磁共振和代谢组学方面的额外培训,这将为她提供重要的新工具,可以作为独立研究者应用于她的研究。 Gary S. Firestein 博士是加州大学圣地亚哥分校的医学教授和转化研究所所长,他将指导首席研究员的科学发展。 Firestein 博士是公认的领导者
类风湿性关节炎的信号转导和发病机制,并在指导医师科学家方面拥有良好的记录。 Michael Karin 博士也是信号转导和炎症领域公认的领导者,他将作为该领域的共同导师提供额外的指导。卡瓦诺博士作为临床导师,将协助利用患者样本开发新型生物标志物。值得注意的是,主要研究者在生物标志物分析滑膜成纤维细胞生物学、以患者为导向的研究和临床试验方面没有经验,这些技能对于过渡为独立研究者至关重要。此外,我们的合作者将帮助使用技术和信息学进行代谢组学研究,解释结果以及如何将其应用于开发新的生物标志物。教学课程、研讨会、期刊俱乐部以及 UCSD 医学系支持性学术环境中实验室技术专门培训的 80% 受保护时间将补充培训计划。该研究计划将重点关注胆碱激酶在与 RA 相关的慢性炎症和关节破坏中的作用。此外,这些研究将确定这种酶是否是治疗炎症性疾病的潜在治疗靶点。我们还将探讨该激酶及其下游产品作为诊断或预后生物标志物的作用。该提案建立在初步研究的基础上,这些研究证明了胆碱激酶在来自 RA 患者的成纤维样滑膜细胞的增殖和存活中具有新的功能。拟议的研究将探索胆碱激酶在 RA 关键信号事件、炎症和关节破坏中的功能和调节。此外,还将在来自 RA 患者的细胞和组织样本中测定胆碱激酶的表达、功能和调节。将确定胆碱激酶代谢模式与临床疾病测量确定的疾病活动之间的关系
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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Monica Guma的其他文献
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