Human Pre-Cancer Models

项目摘要/摘要 核心2：人类癌前模型(HPM)核心 人类癌前模型(HPM)核心将作为一个中央存储库，用于生成、传播和 癌前病变结肠有机体的特性及中性粒细胞和患者匹配的细胞毒/CD8的分离 以及提供技术专业知识来进行关键实验。HPM核心将提供支持 所有这三个项目，并与定量生物科学(QB)核心密切互动。HPM核心的 资源建设将为未来试点和可行性研究的拟议项目和假设生成提供便利。 在赠款的随后几年中，将支持更大规模的合作努力(在TBEL和其他地方) 随着能力和专业知识的扩展，由HPM核心提供。HPM核心将在制度上利用现有的- 支持基础设施和设备，以提供全面注释的人类结肠有机化合物 (正常、SSL和腺瘤)。这些研究中的所有有机化合物都将有广泛的参与者记录 信息和全外显子组测序(WES)以及匹配的生殖系DNA。HPM核心将 利用来自结肠映射的资源获取癌前样本和从GI获得经验 我们已经建立了结直肠癌(CRC)临床前模型的孢子项目，包括患者- 衍生的结直肠癌异种移植物(PDX)和有机体(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个别成分(上皮、微生物、 基质和免疫细胞)。HPM核心将协调努力、整合资源并共享实验 通过追求三个具体目标的专业知识：1)产生和表征上皮、间质和微生物 癌前病变的成分；2)建立上皮细胞与结肠肌动蛋白共培养的条件。 产生大肠杆菌和免疫和/或基质成分；以及3)通过遗传和 药理上的干扰。 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。堆芯 人员将与项目和核心领导密切合作，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TBEL获奖者提供支持。

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.