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.

项目摘要 生物标本和试剂核心[BRC]提供高质量的注释标本和专家病理学 加强P01项目的咨询。BR&C CWRU和杜克组件具有长期的跟踪记录， 支持多研究者基础，转化和临床研究，涉及的多个方面， Barrett食管[BE]和BE-瘤形成。BRC由两个国家认可的胃肠 具有食管病理学专业知识的病理学家，他们在基于组织的 翻译研究布拉迪斯拉发区域中心共同领导人已经合作多年， 与P01团队合作。布拉迪斯拉发区域中心各组成部分拥有不同和互补的资源。 CWRU和杜克组件都有大量的生物档案，用于支持多个 美国国立卫生研究院资助的大型项目超过20年。BR&C有超过1000名 6,200例患者适合本P01。BR&C利用案例CCC共享资源，UH病理学 转化研究中心和杜克生物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对于发现VSIG 10 L的生殖系异常是不可或缺的， 家族性Barrett食管患者中的某些因素。BRC与Prj 1一起定义了敲入 并敲除小鼠模型，这些模型构成了本项目的基础，并确定了多层上皮复合体， 在Prj 1鼠模型中-被认为是BE变化的稳健标志物，并与人类BE相关。 对于项目2，BRC和合作者开发了一种新的方法，使用猪作为模型， 食管损伤-包括食管粘膜下腺体[ESMG]作为潜在起源部位的研究 的BE。在这一努力的启发下，项目2和布拉迪斯拉发区域中心在筛选 多次食管切除术，然后与Prj 2一起进行ESMG免疫分析。分子 所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EPHB 2信号通路的研究，用于确定 BE的发展-其结果构成了该项目的基础。 BRC与Core C将继续为P01调查员提供支持并加强他们的项目 通过提供质量受控的食管组织，人类和动物病理学专业知识， 现有技术组织诊断学包括免疫组织化学、ISH、组织显微切割、空间转录组学 和单细胞测序。