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

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

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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.

地幔细胞淋巴瘤（MCL）是一种非霍奇金淋巴瘤，由于发展而无法治愈耐药性，通常以肿瘤细胞增殖不受约束。细胞周期失调是 MCL的标志。特别是，CDK4的过表达，以及异常的细胞周期蛋白D1表达肿瘤细胞的不受约束的增殖是疾病进展和抗性克隆扩张的基础。但是，MCL耐药性的分子基础仍然晦涩难懂。该计划的总体目标项目是：1）开发基于机制的优质组合疗法，以控制肿瘤的扩展并增强MCL中的肿瘤杀伤，2）阐明耐药性机制，3）基于基因组的患者和治疗分层，以实现最佳和耐用的临床反应。实现这些目标，一个研究人员团队，具有强大的基础科学，癌症研究专业知识，威尔·康奈尔医学（WCM）和俄亥俄州立大学的实验治疗和患者护理 OSU）已将三个交互式项目组装到1）MCL治疗中的目标CDK4； 2）阐明 MCL细胞周期治疗中的FoxO和染色质重塑； 3）在MCl中靶向PRMT5。这些项目由四个杰出的核心支持：1）行政核心，2）病理核心； 3）基因组学和生物信息学核心； 4）生物统计学核心。这些项目和核心都高度整合概念和技术层面，并实时自由共享想法和未发表的数据。 PPG，在首席调查员的带领下，将通过视频会议举行预定的两周会议。即兴讨论，无论是面对面的还是通过电视会议以及频繁的电话和电子邮件。这在咨询中，首席调查员的决策和行政权限链依靠与个人项目和核心领导者。 PPG由由外部顾问委员会支持四名杰出调查人员将参加年度审查会议，在其中进行进展和计划对于每个项目和核心，都会提出讨论和审查。 PPG由内部进一步支持 WCM和OSU的咨询委员会，可以根据需要进行咨询，无论是单独的还是作为小组。研究人员之间以及WCM和OSU之间的协同作用是该PPG的最出色功能并将推动其进步。