program leaders---nuclear receptor

核受体计划是一个由20名NIH资助的基础科学家组成的网络， 了解核受体转录因子和染色质修饰的作用 辅助调节因子对癌症发展的作用。成员共有14，612，144美元的同行评审 研究支持，其中4，167，979美元来自NCI，其余来自其他NIH研究所， 国防部和癌症基金会。该计划的成员有着良好的记录 在基础和临床方面， 整个癌症中心的项目。在过去的三年里，成员发表了202同行 审查的手稿，其中39%是程序内互动的结果，34%来自 有疑问的出版物。一个主要的目标是确定新的治疗目标的成员之间的 核受体超家族和核受体相互作用辅调节蛋白 癌症的治疗干预。为了达到这个目标，我们采取了一个综合的方法， 三个中心组成部分：1）核受体和辅调节子的发现和分析， 调节细胞内稳态的机制，2）它们在癌症中的作用的临床前评估 使用遗传操作的小鼠模型系统的开发，和3）翻译组件 涉及与临床程序的相互作用，以快速将新信息转移到受体分析中， 评估人类癌症的治疗潜力。主要成就包括阐明了 一种乳腺癌细胞选择性翻译后编码，负责pi 60的过表达 辅激活因子I乳腺癌细胞，乳腺癌细胞中的SRC-3; 乳腺癌和前列腺癌转移中的辅激活因子SRC-1和SRC-3;孤儿的发现 核受体NR 4A 1和NR 4A 3作为急性髓性白血病的新型肿瘤抑制剂， 发现它们在人类AML患者中广泛存在的基因沉默， 异质性;以及发现孤儿COUP-TFII作为上皮肿瘤相关性的有效驱动因素 血管生成和转移。

The Nuclear Receptor Program is a network of 20 NIH funded basic scientists focused on understanding the contribution of nuclear receptor transcription factor and chromatic modifying coregulator function to cancer development. Members have a total of $14,612,144 in peer-reviewed research support, $4,167,979 of which is from NCI and the remainder from other NIH institutes, the Department of Defense, and cancer foundation funds. Members of the Program have a strong record of both intraprogramatic collaboration and interprogramatic interactions with both basic and clinical programs throughout the cancer center. During the last three years, members published 202 peer reviewed manuscripts of which 39% were the result of intraprogrammatic interactions and 34% from interrogrammatic publications. A major goal to identify novel therapeutic targets among members of the nuclear receptor superfamily and nuclear receptor interacting coregulator proteins for prevention of and therapeutic intervention in cancer. To achieve this goal, we have adopted an integrative approach with three central components: 1) nuclear receptor and coregulator discovery and analysis of their mechanisms of regulation of cellular homeostasis, 2) preclinical assessment of their roles in cancer development using genetically manipulated mouse model systems, and 3) A translational component involving interaction with clinical programs to rapidly transfer new information into receptor profiling and assessment of therapeutic potential in human cancers. Major accomplishments include elucidation of a breast cancer cell selective posttranslational code that is responsible for overexpression of the pi60 coactivator I breast cancer cells, SRC-3 in breast cancer cells; identification of a critical role of coactivators SRC-1 and SRC-3 in breast and prostate cancer metastases; discovery of the orphan nuclear receptors, NR4A1 and NR4A3 as novel tumor suppressors of acute myeloid leukemia and discovery of their widespread gene silencing in human AML patients regardless of genetic heterogeneity; and discovery of the orphan COUP-TFII as a potent driver of epithelial tumor associated angiogenesis and metastasis.