Epigenomics, RNA and Gene Regulation

表观基因组学、RNA和基因调控研究计划(ERGR) 摘要 表观基因组学、RNA和基因调控研究计划(ERGR)，由Michael Carey博士领导 (计划主任)和Siavash Kurdistani医学博士(计划联合主任)是JCCC研究的最基本的 程序。计划的目标是支持杰出的JCCC研究人员和团队，以确保持续 通过战略招聘和培训实现计划的稳健性，并在基因监管方面创新突破， RNA生物学，以及对癌症有影响的生物信息学。人们的期望是，ERGR调查员发现 将揭示通过新的诊断和抗肿瘤治疗策略进行靶向的漏洞。ERGR 研究人员使用了一系列模型系统，从酵母和植物到癌细胞和小动物，以 阐明基因调控的机制，从染色质和转录到RNA生物学，以了解和 剖析癌症中的变化。项目研究扩展到涉及的生理和病理过程 癌症包括细胞分化、炎症和脂类代谢。ERGR引领开发新的 技术和方法，如用于高通量实验工具的先进信息学，以及 为所有六个JCCC研究项目的研究人员提供专业知识。尽管专注于表观基因组学和 基因调控机制，ERGR努力将新知识转化为临床前和临床环境， 支持临床HDAC抑制剂开发和无细胞DNA诊断的计划发现。 ERGR研究计划有33名成员，来自加州大学洛杉矶分校的五所学校和合作机构加州理工大学， 代表13个部门。截至2019年3月1日，计划支持的直接成本为11,256,579美元， 其中9,904,290美元(88%)是同行审查，1,031,199美元(9%)是NCI资助。计划发现导致 506份上一项目期间的出版物，其中10%是方案内协作，19% 是方案间的协作。此外，271份(54%)计划出版物是与外部合作的 合作者和337(67%)的出版物是在高影响力(如果是≥10或领域领先)期刊上发表的。举个例子， 前一阶段的一项成就是通过招聘大大加强了生物信息学。从科学上讲， 研究揭示了病毒癌基因是如何利用细胞机制来诱导细胞周期并同时阻止 一种抗病毒的免疫反应。此外，对干细胞自身代谢依赖性的新见解 更新和差异化已告知此类依赖关系如何为 在存在预先处理的基因突变的情况下的肿瘤发生。ERGR调查人员培养了一支合议队 有许多有条理的机会来交流思想、研究成果和科学讨论的环境 在项目教职员工、博士后和学生中。这些互动有助于建立有价值的合作， 提高程序科学的质量，激发人们对癌症相关问题的兴趣。一种ERGR节目指南 原则是促进发现基本的生物过程，这些过程的改变可能有助于 癌症的发展和进展，这支持了JCCC战胜这种可怕疾病的最终目标。

EPIGENOMICS, RNA, AND GENE REGULATION RESEARCH PROGRAM (ERGR) ABSTRACT The Epigenomics, RNA, and Gene Regulation Research Program (ERGR), led by Michael Carey, PhD (Program Director) and Siavash Kurdistani, MD (Program Co-Director), is the most basic of the JCCC Research Programs. Program objectives are to support exceptional JCCC researchers and teams, to ensure ongoing Program robustness with strategic recruitments and training, and to innovate breakthroughs in gene regulation, RNA biology, and bioinformatics with impact in cancer. The expectation is that ERGR investigator discoveries will uncover vulnerabilities for targeting by novel diagnostic and anti-tumor treatment strategies. ERGR investigators employ a range of model systems, from yeast and plants to cancer cells and small animals, to elucidate mechanisms of gene regulation, from chromatin and transcription to RNA biology, to understand and dissect alterations in cancer. Program studies extend to physiological and pathological processes implicated in cancer including cell differentiation, inflammation, and lipid metabolism. ERGR leads in developing new technologies and methodologies, such as advanced informatics for high-throughput experimental tools, and provides expertise to researchers in all six JCCC Research Programs. Although focused on epigenomics and gene regulatory mechanisms, ERGR strives to translate new knowledge to preclinical and clinical settings, with Program discoveries underpinning clinical HDAC inhibitor development and cell free DNA diagnostics. The ERGR Research Program has 33 members drawn from five UCLA schools and partner institution, Caltech, representing 13 departments. As of March 1, 2019, Program support was $11,256,579 in direct cost funding, of which $9,904,290 (88%) is peer-reviewed, and $1,031,199 (9%) is NCI funding. Program discoveries resulted in 506 publications during the prior project period, of which 10% were intra-programmatic collaborations, and 19% were inter-programmatic collaborations. In addition, 271 (54%) Program publications were with external collaborators and 337 (67%) of publications were in high-impact (IF ≥10, or field leading) journals. As an example, one achievement in the prior period was enormous strengthening of bioinformatics via recruitment. Scientifically, studies revealed how a viral oncogene exploits cell machinery to induce cell cycling and simultaneously block an anti-viral immune response. Additionally, new insights into the metabolic dependencies of stem cell self- renewal and differentiation informed how such dependencies may provide a permissive environment for tumorigenesis in the presence of pre-disposing genetic mutations. ERGR investigators cultivate a collegial environment with many structured opportunities to exchange ideas, research findings, and scientific discussions amongst Program faculty, postdocs, and students. These interactions help establish valuable collaborations that raise the quality of Program science and inspire interest in cancer-related problems. An ERGR Program guiding principle is to foster the discovery of fundamental biological processes whose alterations may contribute to cancer development and progression, which supports the ultimate JCCC goal of defeating this dreaded disease.