The Role of Intrinsic and Extrinsic Factors in Megakaryocytic-Erythroid Progenitor Lineage Commitment
内在和外在因素在巨核细胞-红系祖细胞谱系承诺中的作用
基本信息
- 批准号:10326464
- 负责人:
- 金额:$ 5.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2022-01-13
- 项目状态:已结题
- 来源:
- 关键词:AffectAlgorithmsAnemiaAreaBioinformaticsBiological AssayBlood CellsBlood PlateletsBlood TransfusionBlood donorBlood-Borne PathogensBone MarrowCD14 geneCell CycleCell divisionCell physiologyCellsCellular biologyChromatinChronicCoculture TechniquesCollaborationsCommunicationDataDerivation procedureDevelopmentDevelopment PlansDiagnosticDoctor of PhilosophyDoseEnsureEnvironmentEpigenetic ProcessErythrocyte TransfusionErythrocytesErythroidFrequenciesGene ExpressionGene TargetingGenesGenetic TranscriptionGenomic SegmentGoalsHematological DiseaseHematopoiesisHematopoieticHematopoietic stem cellsHospitalsHumanImageIn VitroIndividualK-Series Research Career ProgramsLaboratoriesLearningLightMYB geneMarrowMeasuresMediatingMediator of activation proteinMedicineMegakaryocytesMentorsMicroscopyMolecularMolecular BiologyMusOsteoblastsOutcomePathway interactionsPatient-Focused OutcomesPatientsPlatelet TransfusionPlayPostdoctoral FellowProceduresProcessProductionReactionResearchResearch ActivityResearch PersonnelResourcesRiskRoleScienceScience of geneticsSickle Cell AnemiaSignal PathwaySignal TransductionSpecialistSpeedStatistical Data InterpretationTestingTimeTrainingTraining ActivityTransfusionUnderrepresented MinorityWorkblood productcareer developmentcell typechromatin immunoprecipitationepigenomicsexperienceimage processingimprovedimproved outcomeintercellular communicationmacrophagemedical schoolsmemberprogenitorresponse to injuryself-renewalstemstem cellstranscription factortranscriptome sequencingtranscriptomicstransfusion medicinetransmission process
项目摘要
PROJECT SUMMARY
Candidate. Dr. Scanlon, a member of an underrepresented minority, is a third year postdoctoral fellow in the
Department of Laboratory Medicine at Yale School of Medicine with degrees in Molecular Cell Biology, Diagnostic
Genetic Sciences, and Biomedical Science. She is an experimental biologist looking to expand her ability to utilize
algorithms and perform bioinformatic analyses with the long-term goal of becoming an independent investigator. Her
previous training and work with intracellular signaling pathways controlling progenitor cell response to injury combined
with her current work in hematopoiesis uniquely qualify her to conduct the proposed work. The proposed career
development plan will build upon her previous training and enhance her path toward independent research. This plan
includes experimental and didactic learning in image processing, bioinformatic analysis, algorithm optimization, and
advanced statistical analyses to independently analyze massive quantities of data. Development in these areas will
ready her for independent academic molecular and cell biology research in the current era.
Mentor/Advisors and Environment. Dr. Scanlon's primary mentor, Diane Krause, MD, PhD, and imaging
advisor, Dr. Joerg Bewersdorf, PhD will guide Dr. Scanlon through the proposed training and research activities. In addition
to Dr. Krause's extensive experience in mentoring numerous successful academic researchers, and her expertise in
hematopoietic stem and progenitor cells, and Dr. Bewersdorf expertise in high quality live imaging, Dr. Scanlon will also
receive bioinformatic analysis support and learn cell-tracking algorithms through established collaborations with Dr.
Masahiko Sato, developer of cell-tracking algorithms, and Mr. Rolando Garcia-Millian, a dedicated bioinformatic support
specialist at Yale. Dr. Scanlon will meet regularly with her mentor, advisor, and collaborators to ensure her progress. The
proposed career development plan utilizes the expertise and rich resources available at Yale to delineate additional training
activities to facilitate Dr. Scanlon's research.
Research. The molecular mechanisms underlying lineage commitment of hematopoietic stem and progenitor cells
have implications in deriving blood cells in vitro for transfusion medicine, as well as elucidating aberrant pathways
responsible for hematological disorders. Dr. Scanlon's recent postdoctoral work has focused on studying lineage
commitment of Megakaryocytic-Erythroid Progenitors (MEPs). Previous work in the lab identified MYB (a transcription
factor) to be important in controlling human MEP fate, however the mechanism remains elusive. She proposes to use live
imaging to directly visualize MEPs undergoing lineage commitment, as well as transcriptomic and epigenomic approaches
to tease apart the mechanism by which MYB regulates this process. Additionally, she will launch an independent line of
studies investigating the effect of intercellular signaling between MEP and other marrow-residing cells on MEP fate. The
results of these studies may shed light on more general rules of stem and progenitor fate decisions, as well as potentially
help derive patient-specific platelets and red blood cells for transfusions. This career development award will be an
instrumental step in Dr. Scanlon's trajectory towards an independent investigator and leader in hematopoiesis.!
项目摘要
候选人斯坎伦博士,一个代表性不足的少数民族的成员,是一个第三年的博士后研究员在
耶鲁大学医学院实验室医学系,拥有分子细胞生物学、诊断学、
遗传科学和生物医学科学。她是一名实验生物学家,希望扩大她的能力,利用
算法和执行生物信息学分析,长期目标是成为一名独立的研究者。她
以前的培训和工作与细胞内信号通路控制祖细胞对损伤的反应相结合
她目前在造血方面的工作使她有唯一资格开展拟议的工作。提议的职业
发展计划将建立在她以前的培训,并加强她的独立研究的道路。这个计划
包括图像处理,生物信息学分析,算法优化,
先进的统计分析,独立分析大量数据。这些领域的发展将
为她在当今时代进行独立的学术分子和细胞生物学研究做好了准备。
导师/顾问和环境。Scanlon博士的主要导师,Diane Krause,医学博士,医学博士和影像学博士
顾问Joerg Bewersdorf博士将指导Scanlon博士完成拟议的培训和研究活动。此外
Krause博士在指导众多成功的学术研究人员方面的丰富经验,以及她在以下方面的专业知识:
造血干细胞和祖细胞,以及Bewersdorf博士在高质量肝脏成像方面的专业知识,Scanlon博士还将
获得生物信息学分析支持,并通过与Dr.
Masahiko Sato,细胞跟踪算法的开发者,Rolando Garcia-Millian先生,专门的生物信息学支持
耶鲁大学的专家Scanlon将定期与她的导师,顾问和合作者会面,以确保她的进步。的
拟议的职业发展计划利用耶鲁大学的专业知识和丰富的资源来描述额外的培训
为斯坎伦博士的研究提供便利
Research.造血干/祖细胞谱系定向的分子机制
在体外获得用于输血医学的血细胞以及阐明异常途径方面具有意义。
导致血液系统紊乱斯坎伦博士最近的博士后工作集中在研究血统
巨核红系祖细胞(MEPs)的定型。实验室先前的工作确定了MYB(转录
因子)在控制人类MEP命运中是重要的,然而其机制仍然难以捉摸。她建议用生活
成像直接可视化经历谱系定型的MEP,以及转录组学和表观基因组学方法
梳理出MYB调节这一过程的机制。此外,她将推出一个独立的线,
研究MEP和其他骨髓驻留细胞之间的细胞间信号传导对MEP命运的影响。的
这些研究的结果可能会揭示更普遍的规则干和祖命运的决定,以及潜在的
帮助获得患者特定的血小板和红细胞用于输血。这个职业发展奖将是一个
这是斯坎隆医生迈向独立研究者和造血学领导者的重要一步!
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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Vanessa M. Scanlon其他文献
Quantification of intrinsic regulatory factors refines human hematopoietic progenitor definitions and reveals early erythroid lineage priming
内在调节因子的量化细化了人类造血祖细胞的定义,并揭示了早期红系谱系的启动。
- DOI:
10.1016/j.celrep.2025.115913 - 发表时间:
2025-07-22 - 期刊:
- 影响因子:6.900
- 作者:
Patricia Favaro;David R. Glass;Luciene Borges;Reema Baskar;Avery Lam;Warren Reynolds;Daniel Ho;Trevor Bruce;Dmitry Tebaykin;Thomas Koehnke;Vanessa M. Scanlon;Ilya Shestopalov;Sean C. Bendall - 通讯作者:
Sean C. Bendall
Vanessa M. Scanlon的其他文献
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{{ truncateString('Vanessa M. Scanlon', 18)}}的其他基金
The Role of Intrinsic and Extrinsic Factors in Megakaryocytic-Erythroid Progenitor Lineage Commitment
内在和外在因素在巨核细胞-红系祖细胞谱系承诺中的作用
- 批准号:
10615918 - 财政年份:2019
- 资助金额:
$ 5.4万 - 项目类别:
The Role of Intrinsic and Extrinsic Factors in Megakaryocytic-Erythroid Progenitor Lineage Commitment
内在和外在因素在巨核细胞-红系祖细胞谱系承诺中的作用
- 批准号:
10890964 - 财政年份:2019
- 资助金额:
$ 5.4万 - 项目类别:
The Role of Intrinsic and Extrinsic Factors in Megakaryocytic-Erythroid Progenitor Lineage Commitment
内在和外在因素在巨核细胞-红系祖细胞谱系承诺中的作用
- 批准号:
9919548 - 财政年份:2019
- 资助金额:
$ 5.4万 - 项目类别:
The Role of Intrinsic and Extrinsic Factors in Megakaryocytic-Erythroid Progenitor Lineage Commitment
内在和外在因素在巨核细胞-红系祖细胞谱系承诺中的作用
- 批准号:
10581839 - 财政年份:2019
- 资助金额:
$ 5.4万 - 项目类别:
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