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.

项目总结 生物样品和试剂核心[BRC]提供高质量的带注释的标本和专家病理学 咨询以加强P01项目。BR&C CWRU和Duke组件拥有长期的记录 支持多名研究人员进行基础、转化和临床研究，这些研究涉及 Barrett‘s食道和BE瘤。BRC由两个国家公认的胃肠疾病患者共同领导 在食道病理学方面有专业知识的病理学家，在组织病理学方面有良好的跟踪记录 翻译研究。BRC联合领导人多年来一直在一起工作，长期 与P01团队的合作。预算资源中心各组成部分具有差异性和互补性资源。 CWRU和Duke组件都有大型生物档案，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的组织和血液中有来自 6,200名患者适用于此P01。BR&C利用Case CCC共享资源，UH病理 翻译研究核心和杜克生物信息库和精密病理中心共享资源以 最大限度地提高效率，利用他们的专业知识和先进技术。 在项目1中，BRC是发现VSIG10L胚系异常作为易感基因不可或缺的一部分 一些家族性Barrett‘s食道患者的因素。BRC与PRJ 1合作定义了敲击 并剔除了构成该项目基础的小鼠模型，并确定了一种多层上皮复合体 在Prj1小鼠模型中-被认为是BE变化的一个强有力的标记，并与人类的BE有关。 在项目2中，BRC和合作者开发了使用猪作为模型的新方法 食道损伤--包括将食道粘膜下腺[ESMGs]作为潜在起源部位的研究 当然是。在这一努力的启发下，PRJ 2和BRC在筛选期间确定并提供了ESMGs的部分 多次食道切除，然后与Prj2一起工作，以免疫分析ESMGs。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 食管癌发生过程中EPHB2信号转导途径的研究 其成果构成了该项目的基础。 BRC和核心C将继续为P01调查人员提供支持，并将加强他们的项目 通过提供质量受控的食道组织，人类和动物的病理专业知识，并促进状态 ART组织诊断学包括免疫组织化学、原位杂交、组织显微解剖、空间转录学 和单细胞测序。