Asymmetric cell division for fate commitment of human T cells
人类 T 细胞命运决定的不对称细胞分裂
基本信息
- 批准号:10349746
- 负责人:
- 金额:$ 17.33万
- 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:2022-04-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AffectBioinformaticsBiologyBloodCell SeparationCell divisionCellsCellular biologyCellular immunotherapyClinicalCore FacilityDataDaughterDermatologyDevelopmentDevelopment PlansDistalEffector CellEngineeringEnvironmentFOXO1A geneFlow CytometryFunctional disorderFundingGene Expression ProfileGene Expression ProfilingGenetic EngineeringGenetic TranscriptionGermanyGoalsHumanHuman EngineeringImmunotherapyIn SituIn VitroInfectionInflammatoryKnowledgeLabelLaboratoriesLaboratory ResearchLongevityMemoryMentorsMetabolicMetabolic PathwayMetabolismMethodsMitochondriaMitosisMolecularMusOutcomePathway interactionsPatternPennsylvaniaPharmacologyPhenotypePhysiciansPopulationResearchResearch PersonnelResearch TrainingResidenciesScientistSignal PathwaySignal TransductionSkinStructureT cell differentiationT memory cellT-Cell ActivationT-Cell ReceptorT-LymphocyteT-Lymphocyte SubsetsTCR ActivationTechnologyTestingTherapeuticTissuesTrainingUnited States National Institutes of HealthUniversitiesXenograft Modelbasecareer developmentchimeric antigen receptorchimeric antigen receptor T cellschronic inflammatory skindaughter celldesigneffector T cellengineered T cellsexhaustionexperienceexperimental studyfatty acid oxidationgenetic manipulationhuman diseaseimmunological synapseimprovedin vivoinnovationlymphoid organmetabolomicsmouse modelnotch proteinnovelpathogenpost-doctoral trainingpre-clinicalprogramspublic health relevanceself-renewalsingle cell sequencingsingle-cell RNA sequencingskin disorderskin xenograft
项目摘要
Project Abstract
Research: Asymmetric cell division is an evolutionarily conserved mechanism that affords self-renewal,
differentiation and diversification of cell populations. It is unknown, however, if human T cells use this
mechanism to induce distinct daughter cell fates. The proposed research will test the hypothesis that
asymmetric cell division is an indispensable mechanism of human T cells to generate functionally distinct
daughter cells. The experiments will use a novel method of target-induced labeling of the immunological
synapse, multicolor flow cytometry, single cell RNA sequencing and metabolomic profiling to identify and
ultimately modulate cellular programs that support long- and short-lived progeny induction in both native and
genetically-engineered human T cells. A better understanding of cell division patterns will expand our
knowledge on human T cell differentiation, uncover factors promoting niche-specific T cell persistence, and
establish biology-driven principles and methods for optimization of T cell immunotherapy.
Candidate: Dr. Ellebrecht earned his MD from the University of Lubeck, Germany and will complete
Dermatology residency training at the University of Pennsylvania in 2021. Dr. Ellebrecht is pursuing
postdoctoral training in Dr. Aimee Payne’s and Dr. Carl June’s laboratories at Penn. The 5-year career
development plan includes structured coursework and training in single cell transcriptional profiling,
bioinformatics, and metabolic profiling of human T cells from experienced mentors and collaborators, along
with professional career development activities, with the goal of establishing an independent, NIH-funded
research laboratory investigating fate induction and longevity of skin-resident and engineered T cells.
Environment: The mentors, Dr. Aimee Payne and Dr. Carl June, are renowned NIH-funded Penn investigators,
who provide unparalleled expertise in T cell biology, immunotherapy, metabolomics and single cell
characterization of human T cells in combination with an exceptional mentoring record including prior K08 and
K23 awardees. Dr. Ellebrecht’s focus on asymmetric cell division in skin resident T cells provides a clear path
to independence that sets him apart from Dr. Payne’s and Dr. June’s focus on translational immunotherapy.
Dr. Ellebrecht’s research and training will be supported by the Penn Dermatology Department, Center for
Cellular Immunotherapy and CHOP metabolomics core, providing state-of the-art core facilities for flow
cytometry, cell sorting, single cell sequencing, metabolomics, human skin xenografts and bioinformatics. Taken
together, his mentors, collaborators and access to these top-notch technologies will create an ideal
environment for Dr. Ellebrecht to thrive on his path towards becoming an independent physician scientist
leading efforts to characterize and modulate T cell populations responsible for chronic inflammatory skin
diseases.
项目摘要
研究:不对称细胞分裂是一种进化上保守的机制,可提供自我更新、
细胞群的分化和多样化。然而,尚不清楚人类 T 细胞是否使用这种方法
诱导不同子细胞命运的机制。拟议的研究将检验以下假设:
不对称细胞分裂是人类T细胞产生功能独特的不可缺少的机制
子细胞。该实验将使用一种新的免疫学靶标诱导标记方法
突触、多色流式细胞术、单细胞 RNA 测序和代谢组学分析来识别和
最终调节细胞程序,支持本地和短期后代诱导的长寿命和短寿命
基因工程人类T细胞。更好地了解细胞分裂模式将扩大我们的研究范围
关于人类 T 细胞分化的知识,揭示促进利基特异性 T 细胞持久性的因素,以及
建立优化 T 细胞免疫治疗的生物学驱动原则和方法。
候选人:Ellebrecht 博士在德国吕贝克大学获得医学博士学位,并将完成
2021 年在宾夕法尼亚大学接受皮肤科住院医师培训。Ellebrecht 博士正在追求
在宾夕法尼亚大学 Aimee Payne 博士和 Carl June 博士的实验室进行博士后培训。 5年职业生涯
发展计划包括单细胞转录分析的结构化课程和培训,
来自经验丰富的导师和合作者的人类 T 细胞的生物信息学和代谢分析,以及
开展专业职业发展活动,目标是建立一个由 NIH 资助的独立机构
研究实验室研究皮肤驻留和工程 T 细胞的命运诱导和寿命。
环境:导师 Aimee Payne 博士和 Carl June 博士是 NIH 资助的宾夕法尼亚大学著名研究人员,
他们在 T 细胞生物学、免疫治疗、代谢组学和单细胞领域提供无与伦比的专业知识
人类 T 细胞的表征与卓越的指导记录相结合,包括之前的 K08 和
K23 获奖者。 Ellebrecht 博士对皮肤驻留 T 细胞的不对称细胞分裂的关注提供了一条清晰的道路
独立性使他与佩恩博士和琼博士专注于转化免疫疗法不同。
Ellebrecht 博士的研究和培训将得到宾夕法尼亚大学皮肤科中心的支持
细胞免疫治疗和CHOP代谢组学核心,为流程提供最先进的核心设施
细胞计数、细胞分选、单细胞测序、代谢组学、人类皮肤异种移植和生物信息学。采取
他的导师、合作者和这些顶尖技术的共同努力将创造一个理想的
为 Ellebrecht 博士在成为一名独立医师科学家的道路上茁壮成长提供了良好的环境
领导研究和调节导致慢性炎症性皮肤的 T 细胞群的工作
疾病。
项目成果
期刊论文数量(0)
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Christoph Thomas Ellebrecht其他文献
Christoph Thomas Ellebrecht的其他文献
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{{ truncateString('Christoph Thomas Ellebrecht', 18)}}的其他基金
Asymmetric cell division for fate commitment of human T cells
人类 T 细胞命运决定的不对称细胞分裂
- 批准号:
10596213 - 财政年份:2022
- 资助金额:
$ 17.33万 - 项目类别:
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