CELL CYCLING AND SIGNALING PROGRAM

细胞周期和信号程序继续发展，现在已经扩大到包括积极的 表观遗传学、干细胞生物学和肿瘤微环境的项目。这个跨学科的计划 集中于细胞信号和细胞周期控制的调节，以及这些过程中的变化 调节基因表达，引起突变，并促进多步致癌作用。细胞周期是 一个细胞产生两个细胞的生化网络的集合。这就需要协调三个 基本程序：细胞生长、细胞代谢和细胞分裂。细胞分裂，细胞数量的增加 数量，包括遗传物质的适当复制和分离到两个子细胞。 细胞生长，即细胞质量和成分的增加，必须与分裂相协调，以确保适当的细胞分裂。 细胞大小、功能和位置。叠加在这两个基本程序是有区别的 细胞的状态，从干细胞到终末分化。计划成员研究管制入境 进入细胞周期，其中包括适当的分子控制，确保保真度的机制， 过程，以及对生长和分化的外源信号的反应。成员还研究退出 可逆类型（检查点控制、分化）和不可逆类型的细胞周期 （衰老和死亡）。虽然细胞周期机器的核心组成部分是共同的所有 在真核细胞中，调节策略通常对生物体、组织、细胞或细胞具有特异性。 生理/分化状态。这些过程的多个方面通常由核控制 组织（遗传和表观遗传）和来自细胞外基质（肿瘤）的信号 微环境）。在这些基本过程的基础研究所产生的意见， 诊断、预后和疾病预防的临床问题，并最终转化为 制定更好的预防和治疗战略。该程序与几个器官特异性 程序的目的是将这些基本过程应用于特定的肿瘤。许多成员 也属于器官特定的程序，以方便交流。该计划有$18，544，836总同行 审查了上一个预算年度的支助情况。该方案有10%的方案内和25%的方案间 出版物。

The Cell Cycling and Signaling Program has continued to evolve and has now expanded to include active programs in epigenetics, stem cell biology and tumor microenvironment. This interdisciplinary Program focuses on the regulation of cell signaling and cell cycle control and how alterations in these processes modulate gene expression, cause mutations, and fuel multistep carcinogenesis. The cell cycle is the collection of biochemical networks whereby one cell gives rise to two. This entails the coordination of three fundamental programs: cell growth, cell metabolism and cell division. Cell division, the increase in cell number, encompasses the proper replication and segregation of the genetic material to two daughter cells. Cell growth, the increase in cell mass and components, must be coordinated with division to ensure proper cell size, function, and position. Superimposed on both of these fundamental programs is the differentiated status of the cell, ranging from stem cell to terminal differentiation. Program Members study regulated entry into the cell cycle, which include proper molecular controls, mechanisms for ensuring the fidelity of the processes, and responses to exogenous signals for growth and differentiation. Members also study exit from the cell cycle of both the reversible kind (checkpoint control, differentiation) and the irreversible kind (senescence and death). Although core components of the cell cycle machinery are common to all eukaryotic cells, the strategy of regulation is often specific to the organism, the tissue, the cell, or the physiological/differentiated state. Multiple aspects of these processes are often controlled by nuclear organization (both genetic and epigenetic) and by signals from the extra-cellular matrix (tumor microenvironment). Observations resulting from basic research in these fundamental processes are applied to clinical questions of diagnosis, prognosis, and prevention of disease and will ultimately translate into the design of better preventive and therapeutic strategies. This Program interacts with several organ specific programs for the purpose of applying these fundamental processes to specific neoplasias. Many Members also belong to organ-specific Programs to facilitate exchange. The Program has $18,544,836 Total peer reviewed support for the last budget year. The Program has 10% intra-programmatic and 25% interprogrammatic publications.