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
• 负责人: Vanessa M. Scanlon
• 金额: $ 16.52万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615918
• 关键词: Affect; Algorithms; Anemia; Area; Bioinformatics; Biological Assay; Blood; Blood Cells; Blood Platelets; Blood Transfusion; Blood donor; Bone Marrow; CD14 gene; Cell Cycle; Cell division; Cell physiology; Cells; Cellular biology; Chromatin; Chronic; Coculture Techniques; Collaborations; Communication; Data; Dedications; Derivation procedure; Development; Development Plans; Diagnostic; Doctor of Philosophy; Dose; Ensure; Environment; Epigenetic Process; Erythrocyte Transfusion; Erythrocytes; Erythroid; Frequencies; Gene Expression; Gene Targeting; Genes; Genetic Transcription; Genomic Segment; Goals; Hematological Disease; Hematopoiesis; Hematopoietic; Hematopoietic stem cells; Hospitals; Human; Image; In Vitro; Individual; K-Series Research Career Programs; Laboratories; Learning; MYB gene; Macrophage; Marrow; Measures; Mediating; Mediator; Medicine; Megakaryocytes; Mentors; Microscopy; Molecular; Molecular Biology; Mus; Osteoblasts; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Platelet Transfusion; Postdoctoral Fellow; Procedures; Process; Production; Qualifying; Reaction; Research; Research Activity; Research Personnel; Resources; Risk; Role; Science; Science of genetics; Sickle Cell Anemia; Signal Pathway; Signal Transduction; Specialist; Specific qualifier value; Speed; Statistical Data Interpretation; Testing; Training; Training Activity; Transfusion; Underrepresented Minority; Visualization; Work; blood product; career development; cell type; chromatin immunoprecipitation; epigenomics; experience; gene network; image processing; improved; improved outcome; intercellular communication; manufacture; medical schools; member; pathogen; permissiveness; progenitor; response to injury; self-renewal; stem; stem cells; transcription factor; transcriptome sequencing; transcriptomics; transfusion medicine; transmission process

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。 Scanlon博士是代表人数不足的少数民族成员，是第三年的博士后研究员 耶鲁大学医学院实验室医学系，具有分子细胞生物学学位，诊断 遗传科学和生物医学科学。她是一位实验生物学家，希望扩大自己的利用能力 算法和进行生物信息学分析，其长期目标是成为独立研究者。她 先前的培训和使用控制祖细胞响应损伤的细胞内信号通路的工作 由于她目前在造血作品中的工作独特地使她有资格进行拟议的工作。拟议的职业 发展计划将以她以前的培训为基础，并增强她对独立研究的道路。这个计划 包括图像处理中的实验和教学学习，生物信息学分析，算法优化以及 高级统计分析以独立分析大量数据。这些领域的发展将 准备她在当前时代进行独立的学术分子和细胞生物学研究。 导师/顾问与环境。 Scanlon博士的主要导师Diane Krause，医学博士，博士和成像 顾问Joerg Bewersdorf博士博士将指导Scanlon博士通过拟议的培训和研究活动。此外 授予克劳斯博士在指导众多成功的学术研究人员方面的丰富经验，她的专业知识 造血干细胞和祖细胞，以及Bewersdorf博士在高质量实时成像方面的专业知识，Scanlon博士也将 通过与Dr. 细胞跟踪算法的开发商Masahiko Sato和Rolando Garcia-Millian先生是专门的生物信息支持 耶鲁大学的专家。 Scanlon博士将定期与她的导师，顾问和合作者会面，以确保她的进步。这 拟议的职业发展计划利用耶鲁大学可用的专业知识和丰富资源来描述其他培训 促进Scanlon博士研究的活动。 研究。造血茎和祖细胞谱系谱系的分子机制 在体外得出血液细胞对输血医学以及阐明异常途径有影响 负责血液学疾病。 Scanlon博士最近的博士后工作重点是研究血统 巨核细胞 - 侵蚀祖细胞（MEP）的承诺。实验室中的先前工作确定了MYB（转录 因素）对于控制人MEP命运很重要，但是该机制仍然难以捉摸。她建议现场使用 成像直接可视化谱系承诺的MEP以及转录组和表观基因组方法 取笑MYB调节此过程的机制。此外，她将启动一条独立的行 研究了MEP与其他骨髓遗留细胞之间细胞间信号传导对MEP命运的影响。这 这些研究的结果可能会阐明更一般的STEM和祖细胞命运决策的规则，并有可能 有助于引导患者特异性的血小板和红细胞输血。这个职业发展奖将是 Scanlon博士对造血的独立研究者和领导者的轨迹的工具步骤。