Bioreagents & Resources Core

生物试剂

• 批准号: 10713943
• 负责人: JOSEPH EDWARD WILLIS
• 金额: $ 18.6万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713943
• 关键词: Address; Animals; Archives; Barrett Esophagus; Barrett' s carcinogenesis; Basic Science; Biological Assay; Blood; Blood specimen; Body Fluids; Cell Line; Clinical; Clinical Research; Collaborations; Collection; Color; Complex; Comprehensive Cancer Center; Confidentiality of Patient Information; Consultations; Custom; DNA; DNA Library; Development; Diagnostic; Dissection; Dysplasia; EPHB2 gene; Ensure; Epithelium; Esophageal Adenocarcinoma; Esophageal Neoplasms; Esophageal Tissue; Esophageal injury; Esophagectomy; Esophagus; Faculty; Family; Family suidae; Formalin; Freezing; Fresh Tissue; Funding; Genomics; Gland; Goals; High grade dysplasia; Histology; Human; Immunofluorescence Immunologic; Immunohistochemistry; In Situ Hybridization; Inherited; Institutional Review Boards; Investigation; Knock-in; Knockout Mice; Link; Medical Records; Metaplasia; Microdissection; Modeling; Molecular; Morphology; Mus; Outcome; Paraffin Embedding; Pathologist; Pathology; Pathway interactions; Patients; Play; Predisposing Factor; Predisposition; Preparation; Procedures; Program Research Project Grants; Quality Control; RNA; Reagent; Records; Research Personnel; Research Project Grants; Resource Sharing; Resources; Role; Sampling; Schedule; Services; Signal Transduction; Site; Specimen; Submucosa; Susceptibility Gene; Technology; Test Result; Tissue Embedding; Tissue Microarray; Tissue Procurements; Tissue Sample; Tissues; Translational Research; United States National Institutes of Health; Work; biobank; blood fractionation; cancer prevention; carcinogenesis; central database; design; esophageal carcinogenesis; experience; follow-up; gastrointestinal; human tissue; injury and repair; insight; laser capture microdissection; meetings; mouse model; novel; novel strategies; programs; quality assurance; repository; research study; screening; single cell sequencing; skills; success; technology/technique; tissue archive; tissue processing; tissue resource; transcriptomics; wound healing

PROJECT SUMMARY The Biospecimen and Reagents Core [BRC] provides high quality annotated specimens and expert pathology consultation to enhance the P01 projects. The BR&C CWRU and Duke components have long track records of supporting multi-investigator basic, translational and clinical research relating to multiple aspects of the Barrett's Esophagus [BE] and BE- neoplasia. The BRC is co-lead by two nationally recognized gastrointestinal pathologists with expertise in esophageal pathology who have well established track records in tissue-based translational research. The BRC co-leaders have worked together for many years and have longstanding collaborations with the P01 teams. The BRC components have differencing and complementary resources. Both the CWRU and the Duke components have large bioarchives which have been used to support multiple large scale NIH funded projects for over 20+ years. The BR&C has tissue and blood biospecimens from over 6,200 patients suitable for this P01. The BR&C leverages the Case CCC Shared Resources, the UH Pathology Translational Research Core and the Duke BioRepository & Precision Pathology Center shared resource to maximize efficiencies, utilize their expertise and advanced technologies. For Project 1 the BRC was integral to the discovery of germline abnormalities of VSIG10L as a predisposing factor in some patients with Familial Barrett's Esophagus. The BRC worked with Prj 1 to define the knock in and knock out mouse models which form the basis of this project and identified a multilayer epithelium complex in Prj 1 murine models – recognized as a robust marker of BE changes and linked to BE in humans. For Project 2 the BRC and collaborators developed the novel approach of using pigs as a model for esophageal injury – including the study of esophageal submucosal glands [ESMGs] as a potential site of origin of BE. Inspired by this effort, Prj 2 and the BRC identified and provided sections of ESMGs during screening of multiple esophagectomies and then worked with Prj 2 to immunoprofile the ESMGs. The molecular mechanisms identified formed the basis for the project. For Project 3 the BRC supplied high quality tissue samples and immunohistochemistry expertise in the investigation of EPHB2 signaling in esophageal carcinogenesis used to define potential pathways of development of BE – results of which formed the basis for the project. The BRC, with Core C, will continue to provide support to the P01 investigators and will enhance their projects by supplying quality controlled esophagus tissues, human and animal pathology expertise and facilitate state of the art tissue diagnostics including immunohistochemistry, ISH, tissue microdissection, spatial transcriptomics and single cell sequencing.

项目概要 生物样本和试剂核心 [BRC] 提供高质量的带注释样本和专家病理学 咨询以加强P01项目。 BR&C CWRU 和 Duke 组件拥有长期的跟踪记录 支持与多个方面相关的多研究者基础、转化和临床研究 巴雷特食管 [BE] 和 BE- 肿瘤。 BRC 由两位国家认可的胃肠病学专家共同领导 具有食管病理学专业知识的病理学家，在基于组织的研究中拥有良好的跟踪记录 转化研究。 BRC联合领导人已经合作多年，有着悠久的历史 与 P01 团队的合作。 BRC 组件具有差异性和互补性资源。 CWRU 和杜克大学的组件都拥有大型生物档案，可用于支持多个项目 NIH 资助的大型项目已超过 20 年。 BR&C 拥有来自多个国家的组织和血液生物样本 6,200 名患者适合本 P01。 BR&C 利用案例 CCC 共享资源、UH 病理学 转化研究核心和杜克大学生物样本库和精密病理学中心共享资源 最大限度地提高效率，利用他们的专业知识和先进技术。 对于项目 1，BRC 是发现 VSIG10L 种系异常（作为诱发因素）不可或缺的一部分。 一些家族性巴雷特食管患者的因素。 BRC 与 Prj 1 合作定义了敲入 并敲除构成该项目基础的小鼠模型并鉴定出多层上皮复合体 在 Prj 1 小鼠模型中——被认为是 BE 变化的有力标志，并与人类的 BE 相关。 对于项目 2，BRC 和合作者开发了使用猪作为模型的新方法 食管损伤 – 包括将食管粘膜下腺 [ESMG] 作为潜在起源部位的研究 是的。受这一努力的启发，Prj 2 和 BRC 在筛选过程中确定并提供了 ESMG 部分 多次食管切除术，然后与 Prj 2 一起对 ESMG 进行免疫分析。分子 确定的机制构成了该项目的基础。 对于项目 3，BRC 提供了高质量的组织样本和免疫组织化学专业知识 食管癌发生中 EPHB2 信号传导的研究用于确定潜在的途径 BE 的开发——其结果构成了该项目的基础。 BRC 与 Core C 将继续为 P01 研究人员提供支持，并加强他们的项目 通过提供质量受控的食道组织、人类和动物病理学专业知识，并促进状态 先进的组织诊断，包括免疫组织化学、ISH、组织显微切割、空间转录组学 和单细胞测序。