Core A: Administrative Core

核心A：行政核心

基本信息

批准号：
10006526
负责人：
SELINA Y CHEN-KIANG
金额：
$ 19.82万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-18 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10006526
关键词：
Accounting Administrator Agreement Animals Basic Science Bioinformatics Biometry Biostatistics Core Budgets CDK4 gene Cancer Center Cell Cycle Cell Proliferation Clinical Clinical Trials Combined Modality Therapy Consult Consultations Cyclin D1 Decision Making Disease Disease Progression Drug resistance Electronic Mail Equipment and supply inventories Esters Facilities and Administrative Costs Failure Funding Genome Genomics Goals Grant Human Human Resources Individual Institutional Review Boards Investigational Therapies Mantle Cell Lymphoma Manuscripts Medicine Molecular Non-Hodgkin&apos s Lymphoma Ohio Outcome Pathology Patient Care Patients Preparation Principal Investigator Progress Reports Proliferating Protocols documentation Reagent Reporting Research Research Personnel Research Project Grants Resistance Rest Role Schedule Shipping Site Specimen Stratification Teleconferences Telephone Time Treatment Failure Tumor Expansion Universities anticancer research authority base chromatin remodeling data sharing drug development inhibitor/antagonist meetings neoplastic cell novel strategies novel therapeutics overexpression programs response symposium synergism therapeutic target tumor virtual

项目摘要

Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma that remains incurable due to the development of drug resistance, which is typically marked by unrestrained tumor cell proliferation. Cell cycle dysregulation is a hallmark of MCL. In particular, overexpression of CDK4, together with aberrant cyclin D1 expression, drives unrestrained proliferation of tumor cells that underlies disease progression and expansion of resistant clones. However, the molecular basis for drug resistance in MCL remains obscure. The overall goals of the program project are: 1) to develop superior, mechanism-based combination therapies that both control tumor expansion and enhance tumor killing in MCL, 2) to elucidate the mechanism(s) of drug resistance, and 3) to advance genome-based patient and therapy stratification for optimal and durable clinical responses. To achieve these goals, a team of investigators with strong, complementary expertise in basic science, cancer research, experimental therapeutics and patient care at Weill Cornell Medicine (WCM) and The Ohio State University OSU) have assembled three interactive projects to 1) target CDK4 in MCL therapy; 2) to elucidate the role of FOXO and chromatin remodeling in cell cycle therapy for MCL; and 3) to target PRMT5 in MCL. These projects are supported by four outstanding Cores: 1) Administrative Core, 2) Pathology Core; 3) Genomics and Bioinformatics Core; and 4) Biostatistics Core. The projects and cores are highly integrated at both the conceptual and technical levels, with ideas and unpublished data shared freely on a real-time basis. The PPG, led by the Principal Investigator, will hold scheduled bi-weekly meetings via video conferencing in addition to impromptu discussions, both face-to-face or via teleconferences and frequent phone calls and emails. The chain of authority for decision-making and administration rests with the Principal Investigator, in consultation with individual Project and Core leaders. The PPG is supported by an External Advisory Board composed of four distinguished investigators who will participate in the annual review meeting in which progress and plans for each Project and Core are presented for discussion and review. The PPG is further supported by Internal Advisory Boards at WCM and OSU, who are available as needed for consultation, either singly or as a panel. Synergy among Investigators, as well as between WCM and OSU, is the most outstanding feature of this PPG and will propel its progress.

套细胞淋巴瘤 (MCL) 是一种非霍奇金淋巴瘤，由于以下原因仍无法治愈：耐药性，通常以不受限制的肿瘤细胞增殖为标志。细胞周期失调是 MCL 的标志。特别是，CDK4 的过度表达与异常的细胞周期蛋白 D1 表达一起，驱动肿瘤细胞不受限制的增殖是疾病进展和耐药克隆扩张的基础。然而，MCL 耐药的分子基础仍然不清楚。该计划的总体目标项目包括： 1) 开发卓越的、基于机制的联合疗法，既能控制肿瘤扩张并增强 MCL 中的肿瘤杀伤能力，2) 阐明耐药机制，3) 推进基于基因组的患者和治疗分层，以获得最佳和持久的临床反应。为了实现这些目标，一个由在基础科学、癌症研究方面拥有强大、互补的专业知识的研究人员组成的团队，威尔康奈尔医学院 (WCM) 和俄亥俄州立大学的实验治疗和患者护理 OSU）已组建了三个互动项目，以 1）针对 MCL 治疗中的 CDK4； 2）阐明角色 MCL 细胞周期治疗中的 FOXO 和染色质重塑； 3) 以 MCL 中的 PRMT5 为目标。这些项目由四个杰出核心支持：1）行政核心，2）病理学核心； 3) 基因组学和生物信息学核心； 4) 生物统计学核心。项目和核心在两个方面都高度集成概念和技术层面，想法和未发布的数据实时自由共享。 PPG，由首席研究员领导，除即兴讨论，包括面对面或通过电话会议以及频繁的电话和电子邮件。这决策和管理的权力链属于首席研究员，并与他们协商与个人项目和核心领导者。 PPG 得到外部顾问委员会的支持，该委员会由以下人员组成：四位杰出的研究人员将参加年度审查会议，会议的进展和计划每个项目和核心都可供讨论和审查。 PPG 得到了内部的进一步支持 WCM 和 OSU 的顾问委员会可根据需要单独或作为小组进行咨询。研究人员之间以及 WCM 和 OSU 之间的协同作用是该 PPG 最突出的特点并将推动其进步。