Human Pre-Cancer Models

项目总结/摘要 核心2：人类癌前模型（HPM）核心 人类癌前模型（HPM）核心将作为生成、传播和 癌前结肠类器官的表征和中性粒细胞和患者匹配的细胞毒性/CD 8+的分离 T细胞以及提供技术专长进行关键实验。HPM核心将提供支持 所有三个项目，并与定量生物科学（QB）的核心密切互动。HPM核心 资源建设将促进拟议项目和为今后的试点和可行性研究提出假设。 在接下来的几年里，更大的合作努力（在TBEL和其他地方）将得到支持 随着能力和专业知识的扩展，HPM核心将利用现有的，制度上的- 支持的基础设施和设备，以提供全方位的完整注释的人类结肠类器官 （正常、SSL和腺瘤）。这些研究中的所有类器官都将有大量的参与者记录， 沿着匹配的种系DNA的全外显子组测序（WES）。HPM核心将 利用COLON MAP的资源获取癌前标本和GI经验 SPORE项目，我们已经建立了结直肠癌（CRC）的临床前模型，包括患者- 衍生的CRC异种移植物（PDX）和类器官（PDO）。 建立HPM核心是为了支持TBEL应用程序的总体目标，以确定 结肠癌前病变的微环境由其单个组分（上皮，微生物， 基质和免疫细胞）。HPM核心将协调工作，整合资源，并共享实验 通过追求三个特定目标的专业知识：1）产生和表征上皮，基质和微生物 癌前病变的成分; 2）建立上皮细胞与大肠杆菌素的培养和共培养条件， 产生E.大肠杆菌和免疫和/或基质组分;和3）通过遗传和免疫调控来操纵结肠类器官。 药理学干扰。 HPM核心的近期目标是为我们的所有三个项目和QB核心提供支持。核心 工作人员将与项目和核心领导人密切合作，以确保有效的支持和双向沟通。 HPM核心的长期目标是更广泛地传播这些资源和专业知识， 欢迎有机会为其他TBL接受者提供支持。

PROJECT SUMMARY/ABSTRACT Core 2: Human Pre-Cancer Models (HPM) Core The Human Pre-Cancer Models (HPM) Core will serve as a central repository for generation, propagation, and characterization of pre-cancer colonic organoids and isolation of neutrophils and patient-matched cytotoxic/CD8+ T cells as well as providing technical expertise to conduct key experiments. The HPM Core will provide support to all three projects and interact closely with the Quantitative Biosciences (QB) Core. The HPM Core’s resource building will facilitate proposed projects and hypothesis generation for future pilot and feasibility studies. During subsequent years of the grant, larger collaborative efforts (within TBEL and elsewhere) will be supported by the HPM Core as capability and expertise expand. The HPM Core will leverage existing, institutionally- supported infrastructure and equipment to provide a full range of fully-annotated human colonic organoids (normal, SSL, and adenoma). All the organoids in these studies will have an extensive record of participant information and whole-exome sequencing (WES) along with matched germline DNA. The HPM Core will leverage resources from COLON MAP for acquisition of pre-cancer specimens and experience from the GI SPORE projects where we have established preclinical models of colorectal cancer (CRC) including patient- derived CRC xenografts (PDXs) and organoids (PDOs). The HPM Core is established to support the overall goal of the TBEL application in determining how the microenvironment of colonic pre-cancer lesions is shaped by its individual components (epithelial, microbial, stroma, and immune cells). The HPM Core will coordinate efforts, consolidate resources, and share experimental expertise by pursuing three Specific Aims: 1) generate and characterize epithelial, stromal, and microbial components of pre-cancer lesions; 2) establish culture and co-culture conditions of epithelial cells with colibactin- producing E. coli and immune and/or stromal components; and 3) manipulate colonic organoids via genetic and pharmacologic perturbations. The immediate goal of the HPM Core is to provide support to all three of our projects and QB core. Core personnel will work closely with project and core leaders to ensure effective support and two-way communication. The longer-term goal of the HPM Core is the wider dissemination of these resources and expertise as we welcome the opportunity to provide support to other TBEL recipients.