The Role of Intrinsic and Extrinsic Factors in Megakaryocytic-Erythroid Progenitor Lineage Commitment

项目总结 候选人。斯坎伦博士是代表人数不足的少数族裔的一员，是美国大学博士后项目的第三年研究员 耶鲁大学医学院实验室医学系，分子细胞生物学、诊断学学位 遗传科学和生物医学科学。她是一名实验生物学家，希望扩大她利用 并进行生物信息学分析，长期目标是成为一名独立的调查者。她 以前的训练和控制祖细胞对损伤反应的细胞内信号通路的工作相结合 以她目前在造血方面的工作，她唯一有资格进行这项拟议的工作。计划中的职业 发展计划将建立在她之前的培训基础上，并加强她走向独立研究的道路。这个计划 包括图像处理、生物信息学分析、算法优化以及 高级统计分析，可独立分析海量数据。这些地区的发展将 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准备。 导师/顾问和环境。Scanlon博士的主要导师Diane Krause，医学博士，博士和成像学 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 感谢克劳斯博士在指导无数成功的学术研究人员方面的丰富经验，以及她在 和Bewersdorf博士在高质量实时成像方面的专长，Scanlon博士还将 通过与Dr建立合作，获得生物信息学分析支持并学习细胞跟踪算法。 细胞跟踪算法开发者佐藤雅彦和专门的生物信息学支持人员罗兰多·加西亚-米利安 耶鲁大学的专家。斯坎伦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。这个 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规划额外的培训 促进斯坎伦博士研究的活动。 研究。造血干/祖细胞向世系承诺的分子机制 在用于输血医学的体外提取血细胞以及阐明异常途径方面具有重要意义 对血液系统疾病负责。斯坎伦博士最近的博士后工作重点是研究血统 巨核细胞-红系祖细胞(MEP)的承诺。实验室之前的工作确定了MYB(一种转录 因素)在控制人类MEP命运中起着重要作用，然而其机制仍不清楚。她提议使用LIVE 成像以直接可视化正在经历谱系承诺的欧洲议会议员，以及转录和表观基因组学方法 梳理MYB调节这一过程的机制。此外，她还将推出一条独立的 研究MEP和其他骨髓细胞之间的细胞间信号对MEP命运的影响。这个 这些研究的结果可能有助于阐明茎和祖先命运决定的更一般规则，以及潜在的 帮助提取患者特有的血小板和红细胞用于输血。这个职业发展奖将是一个 在斯坎隆博士成为一名独立的研究人员和造血学领导者的道路上，迈出了重要的一步。

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.!