The Center for Therapeutic Targeting of EWS-oncoproteins

EWS癌蛋白治疗靶向中心

• 批准号: 10671815
• 负责人: SCOTT A ARMSTRONG
• 金额: $ 50.54万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-07 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10671815
• 关键词: Award; Basic Science; Biology; Chemicals; Chimeric Proteins; Clinic; Clinical Research; Complex; Computational Biology; Development; Disease; EWS-FLI1 fusion protein; Epigenetic Process; Ewings sarcoma; Functional disorder; Genetic Transcription; Goals; Individual; Industrialization; Institution; Investigational Therapies; Knowledge; Malignant Neoplasms; Molecular; Oncogenic; Oncoproteins; Parents; Pediatric Oncologist; Process; Proteins; Research; Talents; Technology; Therapeutic; Therapeutic Clinical Trial; Translations; Validation; bone; clinical translation; drug development; improved outcome; mouse model; novel; novel therapeutics; pediatric patients; pre-clinical; sarcoma; skills; structural biology; success; therapeutic target; tool; translational scientist; tumorigenesis

PROJECT SUMMARY: Overall This section is unchanged from the U54 CA231637 parent award The primary scientific focus of this Center is to understand the molecular underpinnings of EWS-ETS driven Ewing sarcoma and to investigate novel treatments and therapeutic mechanisms to improve outcomes for pediatric patients with this aggressive disease. Translation of molecular understanding of sarcoma pathophysiology into effective new drugs in the clinic is a complex, risky proposition that requires the coordinated efforts of a talented team of individuals with complementary skills. This group brings expertise in Ewing sarcoma biology and the EWS-ETS oncoproteins, epigenetics and transcription, structural biology, computational biology, chemical biology and drug development, mouse models, preclinical experimental therapeutics, and clinical trials development. A Center mechanism is essential to the success of this proposal. No one institution nor individual can bring mastery of the diversity of approaches, technologies, and scientific domains needed to achieve the goals of this proposal. We have elected to focus on understanding the fundamental inner workings of Ewing sarcoma from its transcriptional circuits, to the direct protein interactions with EWS-FLI1, to the direct and immediate effects of EWS-FLI1 degradation. Moreover, a strong emphasis of this proposal is on target identification and preclinical validation, critical steps in the process of bringing forward therapies with optimal chances for success in the clinic. The team that is assembled has all of the component pieces needed for success. Our Center includes outstanding basic cancer biologists, chemists, computational biologists, and translational researchers, and five pediatric oncologists. Thus, the proposed Center can catalyze basic discovery and clinical translation by leveraging basic and clinical research talent within the Center and our strong ties to outside academic and industrial partners.

项目概要：总体 此部分与U54 CA231637家长奖相同 该中心的主要科学重点是了解 EWS-ETS 驱动的分子基础 尤文肉瘤并研究新的治疗方法和治疗机制以改善结果 患有这种侵袭性疾病的儿科患者。肉瘤的分子认识翻译 将病理生理学转化为临床上有效的新药是一个复杂且有风险的命题，需要 一个由具有互补技能的人才组成的团队的协调努力。该小组带来了以下方面的专业知识 尤文肉瘤生物学和 EWS-ETS 癌蛋白、表观遗传学和转录、结构生物学、 计算生物学、化学生物学和药物开发、小鼠模型、临床前实验 疗法和临床试验开发。中心机制对于该提案的成功至关重要。 没有任何一个机构或个人能够掌握多种方法、技术和科学 实现本提案目标所需的领域。我们选择专注于了解 尤文肉瘤的基本内部运作方式，从转录回路到直接的蛋白质相互作用 与 EWS-FLI1 一起使用，对 EWS-FLI1 降解产生直接和立即的影响。此外，强烈强调 该提案的重点是目标识别和临床前验证，这是引入过程中的关键步骤 推进治疗，以在临床上获得最佳成功机会。组建的团队拥有所有 成功所需的组成部分。我们的中心包括杰出的基础癌症生物学家、化学家、 计算生物学家、转化研究人员以及五名儿科肿瘤学家。因此，建议的 中心可以利用基础和临床研究人才来促进基础发现和临床转化 中心内部以及我们与外部学术和工业合作伙伴的紧密联系。

项目成果

DisP-seq reveals the genome-wide functional organization of DNA-associated disordered proteins.

DisP-seq 揭示了 DNA 相关无序蛋白质的全基因组功能组织。

• 发表时间: 2024-01
• 影响因子: 46.9
• 作者: Xing, Yu;Dong, Rui;Lee, Lukuo;Rengarajan, Shruthi;Riggi, Nicolò;Boulay, Gaylor;Rivera, Miguel N
• 通讯作者: Rivera, Miguel N