Administrative Core

项目概要-行政核心 患有NUP 98重排的急性白血病的儿童对常规治疗的反应较差， 与疾病复发率高和预后差相关。这些融合约占 10%的AML儿童，但我们对融合癌蛋白的分子后果的总体理解 由于缺乏合适的模型系统，表达受到了部分限制，这反过来又阻碍了 制定合理的、有针对性的治疗方法。FusOnC 2中心的总体目标 NUP 98急性白血病的实验和临床前建模是为了了解机制基础 并开发和翻译新的，更有效的治疗方法，这种形式的白血病。 白血病这些目标将通过四个研究项目来实现，这些项目将利用三个核心设施， 行政，基因组编辑和化学生物学在四个学术研究中心：圣裘德儿童 研究医院，纪念斯隆凯特琳癌症中心，达纳法伯癌症研究所和希望之城。 该项目将在小鼠和小鼠中进行NUP 98和伴随的基因组病变的实验建模， 人类模型和化学试剂的测试活性（项目1）;检查NUP 98融合对 转录和染色质复合体组装（项目2）;检查相分离在 白血病发生中的转录失调（项目3）;开发和测试新的小分子和 降解物治疗方法（项目4）。该中心将高度互动和协作， 项目和核心之间的互动协同作用，以加快发现和翻译的步伐， 这种高风险的白血病行政核心将设在圣裘德， 管理团队，行政，赠款和项目管理援助。行政核心将 为进度会议、现场会议和FusOnC 2会议提供行政支持， 管理，内部和外部数据共享和网站，确保遵守所有机构，国家 和联邦法规，并协调定期向NIH报告研究活动。

PROJECT SUMMARY – Administrative Core Children with NUP98-rearranged acute leukemias demonstrate a poor response to conventional therapy and are associated a high rate of relapsed disease and poor outcome. These fusions account for approximately 10% of children with AML, yet our overall understanding of the molecular consequences of fusion oncoprotein expression has been limited in part by a paucity of suitable model systems, which in turn has prevented the development of rational and targeted therapeutic approaches. The overarching goals of the FusOnC2 Center for Experimental and Preclinical Modeling of NUP98 Acute Leukemia are to understand the mechanistic basis of leukemogenesis and develop and translate new, more effective therapeutic approaches for this form of leukemia. These goals are to be accomplished in four research projects utilizing three core facilities, Administrative, Genome Editing and Chemical Biology in four academic research centers: St Jude Children’s Research Hospital, Memorial Sloan Kettering Cancer Center, Dana Farber Cancer Institute, and City of Hope. The projects will perform experimental modeling of NUP98 and concomitant genomic lesions in mouse and human models and test activity of chemical agents (Project 1); examine the role of NUP98 fusions on transcriptional and chromatin complex assembly (Project 2); examine the role of phase separation in transcriptional deregulation in leukemogenesis (Project 3); and develop and test new small molecule and degrader therapeutic approaches (Project 4). The Center will be highly interactive and collaborative, with interactions between projects and cores synergizing to accelerate the pace of discovery and translation for this high risk form of leukemia. The Administrative Core will be located at St Jude and comprise an Executive Management Team, administrative, grants and project management assistance. The Administrative Core will facilitate administrative support for progress meetings, on site and FusOnC2 meetings, financial management, internal and external data sharing and website, ensure compliance with all institutional, state and federal regulations, and coordinate periodic reporting of research activity to the NIH.