Blood Cell Development and Function Program (02)

项目总结/摘要-血细胞发育和功能研究 血细胞发育和功能（BCDF）计划由Balachandran和Wiest领导， 由21名主要成员和6名合作成员组成。计划资金为700万美元（项目直接成本），其中 610万美元是同行评审的，190万美元来自NCI。除了资助实验室研究人员外，该计划 包括7名临床医生/临床研究人员，他们的专业知识和转化科学兴趣对国际合作至关重要， 和项目内合作，并加快将研究成果转化为新的见解， 为患者治疗。计划成员的工作效率高，互动性强：305份出版物中有11%是 17%是方案内的，31%是在高影响力的期刊上发表的。 BCDF计划的科学使命是确定控制细胞命运决定的扰动如何能够 导致血癌的发展，以描述实体瘤内的炎症如何影响 肿瘤进展，并利用免疫系统细胞与其细胞之间的独特相互作用， 改善癌症免疫治疗的目标。所有参加这个基础科学项目的人都参与了癌症- 相关研究，在过去的资助周期中，许多基础科学观测已经推进到 专注于研究。突出的例子强调了这种“从基本到翻译”的轨迹。 该计划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，并评估其与血液恶性肿瘤病因学的相关性（发展主题）; 2)定义炎症反应如何预防或控制感染，并将这些知识应用于如何 癌症的发展以及如何靶向它们（炎症主题）;以及3）探索 免疫细胞及其可溶性产物（例如，干扰素）的控制，最终目的是利用这些 识别对免疫疗法无反应的患者，并将这些见解应用于逆转 免疫衰竭和恢复强有力抗肿瘤免疫应答。具体而言，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 受益于这些方法（一个发展中的免疫效应器主题）。共同的科学兴趣 该计划的调查人员，加上新的和现存的跨计划和计划内的合作，使 这些主题相互联系协同作用。该计划中的研究者从CCSG中受益匪浅- 支持共享资源，并在很大程度上依赖于动物模型的建立和使用。因此，委员会认为， 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 老鼠设施此外，尖端技术也进一步这些主题，包括多参数流 细胞计数，激光捕获显微切割，下一代测序，过继细胞转移，基因组 使用锌指核酸酶或CRISPR/Cas9进行编辑，并通过Cell完成拷贝数分析。 培养、生物成像、基因组学和组织学设施。

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.