Core A: Administrative Core

套细胞淋巴瘤(MCL)是一种非霍奇金淋巴瘤，由于疾病的发展而无法治愈。 耐药，典型的特征是肿瘤细胞不受抑制的增殖。细胞周期失调是一种 MCL的标志。特别是，CDK4的过表达和细胞周期蛋白D1的异常表达共同驱动 肿瘤细胞的不受限制的增殖，这是疾病发展和耐药克隆扩张的基础。 然而，MCL耐药的分子基础仍不清楚。该计划的总体目标 项目是：1)开发优越的、基于机制的联合疗法，既能控制肿瘤的扩散 2)阐明耐药机制(S)，3)促进MCL的肿瘤杀伤 基于基因组的患者和治疗分层，以实现最佳和持久的临床反应。要实现这些目标 Goals，一支在基础科学、癌症研究、 威尔·康奈尔医学(WCM)和俄亥俄州立大学的实验治疗学和病人护理 OSU)组织了三个互动项目：1)针对CDK4在MCL治疗中的作用；2)阐明CDK4在MCL治疗中的作用 FOXO和染色质重塑在MCL细胞周期治疗中的作用；3)靶向MCL中的PRMT5。这些项目 有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。项目和核心都高度集成在 概念和技术层面，想法和未发布的数据实时自由共享。PPG， 由首席调查员领导，将通过视频会议每两周举行一次预定会议，此外 即兴讨论，面对面或通过电话会议和频繁的电话和电子邮件。这个 决策和行政的权力链由首席调查员协商决定 与个别项目和核心领导进行沟通。PPG由一个外部咨询委员会提供支持，该委员会由以下人员组成 将参加年度审查会议的四名杰出调查人员，会议上的进展和计划 为每个项目和核心提出讨论和审查。PPG得到了内部的进一步支持 WCM和OSU的咨询委员会，可根据需要单独或作为小组进行咨询。 调查人员之间以及WCM和OSU之间的协同是这一PPG最突出的特点 并将推动其进步。

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 The projects and cores are highly integrated at both the conceptual and technical levels, with ideas and unpublished data shared freely on a real-time basis.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.