Core C: Sphingolipid Cancer Animal Pathology Core

摘要 鞘磷脂动物癌症病理生物学(SACP)共享资源的总体目标是提供 本项目项目负责人具备充分有效利用本项目的知识、资源和能力 动物模型在执行他们的研究项目和推进他们的临床前研究方面的作用。通过 SACP核心，这些项目利用基因工程小鼠模型(GEMM)来研究 癌症发生和转移的机制，特别是利用一组独特的动物 神经鞘脂代谢相关基因缺失与特发性骨质疏松症动物模型的相关性 癌症。事实上，SACP已经成为神经鞘脂基因敲除小鼠的国家储存库，已经产生了 他们中的几个。 癌症的临床前模型，特别是动物模型，对于识别和 验证新的功能、干预措施、治疗靶点和生物标记物。因此，核心将提供 这些项目具有在研究项目中利用体内模型的从头到尾的专业知识。核心意志 协助一)动物模型选择；二)生成致癌动物模型，包括生成 新的GEMM；iii)患者来源的异种移植(PDX)的开发和使用以及人类细胞的植入 活体内；四)未来和/或合作研究样本的生物库；和五)获取和使用关键相关的 通过癌症中心和/或大学提供的共享资源。SACP核心将提供 为项目高效和有效地进行体内研究提供了框架。 为此，SACP核心将：具体目标1：向调查人员提供必要的资源，以 实施体内癌症模型；具体目标2：能够执行临床前和转化性 致癌模式和样本生物库；以及具体目标3：提高影响 通过使用共享资源、动物模型替代方案和数据进行体内研究 管理层。 SACP核心的服务和专业知识将促进本提案中概述的活体研究，并将 提供专业知识来支持项目负责人。通过整合致癌模型和 GEMM在鞘脂中，这一核心正在演变为一个独特的赋能核心，这是成功的关键 计划项目及其对临床前研究的进展。

ABSTRACT The overall objective of the Sphingolipid Animal Cancer Pathobiology (SACP) Shared Resource is to provide the Project leaders of this Program Project with the knowledge, resources and ability to fully and efficiently utilize animal models in the execution of their research projects and to advance their preclinical studies. Through the SACP core, the projects utilize genetically engineered mouse models (GEMM) for the investigation of the mechanisms involved in carcinogenesis and metastasis, specifically utilizing a unique set of animals with deletions in genes of sphingolipid metabolism coupled with pathologically-relevant animal models of specific cancers. Indeed, the SACP has become a national repository for sphingolipid knock out mice, having generated several of them. Preclinical models, specifically animal models, of cancer are invaluable tools for the identification and validation of novel functions, interventions, therapeutic targets, and biomarkers. Therefore, the Core will provide the projects with “start-to-finish” expertise in utilizing in vivo models in their research projects. The Core will assist with i) animal model selection; ii) generation of animal models of carcinogenesis, including the generation of novel GEMM; iii) development and use of patient-derived xenografts (PDXs) and engraftment of human cells in vivo; iv) BioBanking of samples for future and/or collaborative studies; and v) access and use of critical relevant shared resources available throught the Cancer Center and/or University. The SACP Core will provide the framework for the projects to efficiently and effectively conduct in vivo resarch. To this end the SACP Core will: Specific Aim 1: Provide investigators with the necessary resources to implement in vivo models of cancer; Specific Aim 2: Enable the execution of preclinical and translational models in carcinogenesis, as well as BioBanking of samples; and Specific Aim 3: Advance the impact of in vivo research through the use of Shared Resources, animal model alternatives, and data management. The services and expertise of the SACP Core will facilitate in vivo research outlined in this proposal and will provide the expertise to support the Project Leaders. With the incorporation of carcinogenesis models and GEMM in sphingolipids, this Core is evolving as a unique and enabling Core that is critical for the success of the Program Projects and their advancement to preclinical studies.