Blood Cell Development and Function Program (02)

项目摘要/摘要-血细胞开发和功能规划 血细胞发育和功能(BCDF)计划由Balachandran和Wiest领导，并 由21名主要成员和6名协作成员组成。方案资金为700万美元(项目直接成本)，其中 610万美元来自同行评审，190万美元来自NCI。除了资助实验室调查人员外，该计划还 包括7名临床医生/临床研究人员，他们的专业知识和翻译科学兴趣对于 和方案内协作，并加快将研究成果转化为新的见解和 对病人的治疗。计划成员工作效率高，互动性强：305种出版物中有11%是 方案内，17%是方案间，31%发表在影响较大的期刊上。 BCDF计划的科学使命是定义控制细胞命运决定的扰动如何 导致血癌的发展，以描绘实体肿瘤内的炎症如何影响 肿瘤进展，并利用免疫系统细胞和它们之间独特的相互作用 目标是提高癌症免疫治疗水平。这个基础科学计划的所有成员都参与了癌症- 相关研究，在过去的资助周期中，许多基础科学观测进展到 以翻译为主的研究。突出的例子强调了这种“从基础到翻译”的轨迹。 该方案的使命是通过三个相互关联的主题来实现的：1)确定控制 造血及其与恶性血液病病因学的相关性(发展主题)； 2)确定炎症反应如何预防或控制感染，并将这一知识应用于如何 癌症的发展及其如何成为靶点(炎症主题)；以及3)探索 免疫细胞及其可溶性产物(如干扰素)受到控制，最终目的是利用这些 识别对免疫治疗无效的患者的见解，并将这些见解应用于逆转 免疫衰竭，恢复旺盛的抗肿瘤免疫反应。具体地说，BDCF调查人员寻求 在治疗前确定无应答者，并确定如何扩大可以 从这些方法中受益(一个发展中的免疫效应器主题)。他们之间的共同科学兴趣 本计划的调查人员，加上新的和现有的计划间和计划内合作，使 将这些主题相互联系起来的协同效应。本计划内的调查人员从CCSG- 支持共享资源，严重依赖动物模型的建立和使用。因此， 许多人是实验动物设施的主要用户，包括其斑马鱼模块和转基因生物 鼠标设施。其他尖端技术也推动了这些主题，包括多参数流动 细胞学、激光捕获显微切割、下一代测序、过继细胞转移、基因组 用锌指核酸酶或CRISPR/Cas9进行编辑，并进行拷贝数分析，通过细胞完成 培养、生物成像、基因组学和组织病理学设施。

PROJECT SUMMARY/ABSTRACT – BLOOD CELL DEVELOPMENT AND FUNCTION PROGRAM The Blood Cell Development and Function (BCDF) Program is led by Balachandran and Wiest, and is comprised of 21 Primary and 6 Collaborating Members. Program funding is $7M (project direct costs) of which $6.1M is peer-reviewed and $1.9M is from the NCI. In addition to funded laboratory investigators, the Program includes 7 clinicians/clinical researchers, whose expertise and translational scientific interests are vital to inter- and intra-programmatic collaborations, and to accelerate translation of research findings to new insights and treatments for patients. Program members are highly productive and interactive: 11% of 305 publications are intra-programmatic, 17% are inter-programmatic, and 31% were published in high-impact journals. The scientific mission of the BCDF Program is to define how perturbations in control of cell fate decisions can lead to the development of blood cancers, to delineate how inflammation within a solid tumor can influence tumor progression, and to capitalize on the unique interactions between cells of the immune system and their targets to improve cancer immunotherapy. All members of this basic science program participate in cancer- relevant research, and over the past funding cycle, many basic science observations have advanced to translationally-focused studies. Highlighted examples underscore this “basic-to-translation” trajectory. The mission of the Program is pursued through three inter-related themes: 1) to define processes that control hematopoiesis and assess their relevance to the etiology of hematologic malignancies (Development theme); 2) to define how the inflammatory response prevents or controls infections, and to apply that knowledge to how cancers develop and how they can be targeted (Inflammation theme); and 3) to explore how the action of immune cells and their soluble products (e.g., interferons) is controlled, with the ultimate aim of exploiting these insights to identify patients that are unresponsive to immunotherapy and to apply these insights to reverse immune exhaustion and restore vigorous anti-tumor immune responses. Specifically, BDCF investigators seek to identify non-responders prior to treatment and determine how to expand the number of patients who could benefit from such approaches (a developing Immune Effectors theme). Common scientific interests among investigators in this Program, coupled with new and extant inter- and intra-programmatic collaborations, enable synergies that interconnect these themes. Investigators within this Program benefit extensively from CCSG- supported Shared Resources, and rely heavily on the establishment and use of animal models. Consequently, many are major users of the Laboratory Animal Facility, including its zebrafish module, and the Transgenic Mouse Facility. Additional, cutting-edge technologies also further these themes, including multi-parametric flow cytometry, laser capture microdissection, next-generation sequencing, adoptive cellular transfers, genome editing with Zinc finger nucleases or CRISPR/Cas9, and copy number analysis, accomplished through the Cell Culture, Biological Imaging, Genomics, and Histopathology Facilities.