Endogenous circadian clocks regulate NG2-glia regenerative potential
内源性生物钟调节 NG2 神经胶质细胞的再生潜力
基本信息
- 批准号:10807543
- 负责人:
- 金额:$ 18.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-26 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:ARNTL geneAddressAdultAffectAffinity ChromatographyAmericanAutopsyBindingBrainBrain InjuriesCSPG4 geneCause of DeathCellsChildChromatinChronobiologyCircadian RhythmsCodeCollaborationsCritical CareDNA BindingDNA-Protein InteractionDataDeoxyuridineDependenceDevelopmentDevelopment PlansDevelopmental BiologyDiseaseEducational process of instructingEpidemicEvaluationFeedbackFoundationsFundingFutureGene ExpressionGene ProteinsGene TargetingGenesGenetic TranscriptionGoalsHeadHealthHealth SciencesHeterogeneityHospitalsHumanImmunohistochemistryIn VitroInjuryInstitutionLaboratoriesMapsMeasuresMedicineMentorsMethodsMolecularMusNatural regenerationNervous System TraumaNeurogliaNeurosciencesPathologyPathway interactionsPatientsPediatricsPeriodicityPersonsPhasePhysiciansPopulationPositioning AttributeProcessProliferatingPropertyProteinsPublic HealthPublishingRegenerative MedicineReportingResearchResearch PersonnelRestRibosomesRoleScienceScientistSystemTBI treatmentTechniquesTestingTherapeuticTimeTissuesTrainingTransgenic OrganismsTranslatingTraumatic Brain InjuryTraumatic Brain Injury recoveryUnited StatesUniversitiesWashingtonWritingagedbench to bedsidecareercareer developmentcell regenerationcell typecircadiancircadian biologycircadian pacemakerclinically relevantconditional knockoutcostdifferential expressiondisabilityexperiencemedical schoolsmouse modelpre-clinical researchprofessorprogramsregeneration following injuryregeneration potentialregenerativeregenerative cellregenerative therapyresponseskillstargeted treatmenttherapy developmenttranscription factortranscriptome sequencingtranslatomewhite matter
项目摘要
PROJECT SUMMARY/ABSTRACT
Traumatic brain injury (TBI) is the leading cause of death and disability in patients aged 1-44 years. While there
is no treatment for TBI, one potential strategy is to harness the brain’s native capacity for cellular regeneration
to replace lost cells. NG2-glia, the largest population of regenerative cells in the adult CNS, can proliferate and
differentiate into multiple glial cell types; uncovering the molecular pathways regulating these NG2-glia
processes is a key step to develop future therapies for TBI. The candidate previously found that cortical NG2-
glia are regulated by the molecular circadian clock, a well-characterized 24-hr transcriptional-translational
feedback loop, with a key contribution by the clock gene Bmal1. However, the mechanism by which the clock
affects regenerative potential as well as the generalizability of this mechanism to other NG2-glia (e.g. white
matter NG2-glia) are unknown. In this proposal, the candidate hypothesizes that the NG2-glia endogenous
circadian clock directly governs molecular pathways to regulate regenerative potential, both in health and
disease. He will test this hypothesis with the following aims: 1) Determine the clock-dependence of cortical and
white matter NG2-glia proliferation and differentiation in the healthy brain and in response to TBI; 2) Identify the
clock-dependent molecular programs regulating cortical NG2-glia proliferation in the healthy and injured brain;
3) Define the differential expression of BMAL1 target genes during basal and injury-induced cortical NG2-glia
proliferation. Successful completion of these aims will identify the clock-dependent molecular pathways
underlying NG2-glia regenerative potential that will serve as future targets to manipulate post-TBI cellular
regeneration. Currently holding positions as Attending Physician in Critical Care Medicine at Children’s National
Hospital and Assistant Professor of Pediatrics at George Washington University School of Medicine and Health
Sciences, the candidate is committed to a career in academic medicine. With >75% protected time, as supported
by his institution, the candidate will be guided by his primary mentor (Vittorio Gallo) and co-mentors (Kazue
Hashimoto-Torii, Amita Sehgal, Regina Armstrong). He has access to laboratory space, supplies, and research
funding to carry out the proposed project. His career development plan is comprised of hands-on training and
didactics to accomplish his training goals, which includes technical and non-technical skills necessary for future
independence. From a technical aspect, he seeks training in in vitro techniques, human post-mortem tissue
evaluation, and omics sciences; there is a focus on the last, as his proposal uses translatomics and chromatin
mapping, two approaches ideally suited for investigating the changes in NG2-glia molecular programs induced
by the transcription factors comprising the circadian clock. Completion of his training plan will permit the
candidate to conduct studies on a variety of scales, allowing him to fulfill the “bench to bedside” mantra that
motivates him to tread the path of a physician scientist. Furthermore, he will have positioned himself as an
investigator at a unique intersection of circadian rhythms, neurotrauma, and regenerative medicine.
项目总结/文摘
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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Terry Dean其他文献
Terry Dean的其他文献
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{{ truncateString('Terry Dean', 18)}}的其他基金
Role of Shaker Channel Function in the Regulation of Sleep in Drosophila
Shaker Channel 功能在果蝇睡眠调节中的作用
- 批准号:
8201103 - 财政年份:2010
- 资助金额:
$ 18.24万 - 项目类别:
Role of Shaker Channel Function in the Regulation of Sleep in Drosophila
Shaker Channel 功能在果蝇睡眠调节中的作用
- 批准号:
7809143 - 财政年份:2010
- 资助金额:
$ 18.24万 - 项目类别:
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