Clinical Transplant Centers

临床移植中心

• 批准号: 7979525
• 负责人: Daniel R. Salomon
• 金额: $ 29.74万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7979525
• 关键词: Acute; Adult; Adverse event; African American; Archives; Biology; Biopsy; Candidate Disease Gene; Caucasoid Race; Chronic rejection of renal transplant; Clinical; Clinical Data; Clinical Investigator; Clinical Research; Data; Data Analyses; Databases; Enrollment; Event; Gene Expression; Gene Expression Profiling; Gene Proteins; Genetic; Genomics; Genotype; Hispanics; Immune response; Immunosuppression; Informed Consent; Kidney Transplantation; Leadership; Molecular; Molecular Profiling; Monitor; Multicenter Trials; Organ Donor; Outcome; Pathway interactions; Patients; Principal Investigator; Proteomics; Protocols documentation; Reporting; Research Ethics Committees; Research Personnel; Running; SNP genotyping; Scientist; Specific qualifier value; Specimen; Specimen Handling; Subgroup; Testing; Therapeutic; Time; Transplantation; United States; Visit; base; experimental analysis; follow-up; insight; meetings; peripheral blood; programs; prospective; protein expression; response; sex; statistics; success; web site

The Clinical Transplant Center Core will be comprised of 10 major academic transplant centers in the United States doing approximately 1360 adult kidney transplants per year in total. Its activities will be integrated with the three Scientific Projects through the Clinical Database, the Program Project website, yearly scientific meetings and active interim interactions between the 10 Clinical Investigators and the Principal Investigators. Our focused objectives for this Core are to provide the Projects with the requisite patient materials and correlating clinical data to test the hypotheses that: 1) gene expression and proteomic signatures in PBL and kidney transplant biopsies can be identified that correlate with biopsy-proven acute rejection and chronic allograft nephropathy, 2) gene and protein expression profiles will provide insights into the molecular pathways involved in both the host immune response and the donor organ's response to transplantation, 3) the adequacy of immunosuppression as defined by the absence of rejection-related gene and protein expression can be determined at any given time by gene and protein expression profiles, and 4) targeted SNP genotyping and candidate gene sequence studies will identify connections between the genetics of the donor and the recipients that correlate with transplant events and outcomes as well as with gene and protein expression signatures. Arching over all these hypotheses, we propose to examine the possibility that race (Caucasian, African American and Hispanic) and/or sex will genetically influence at least a subset of genes and proteins expressed post transplant and correlate with clinical outcomes. A critical point is that the correct clinical designations of the patient subgroups and successful completion of enrollment and specimen acquisitions, the two primary tasks for this Core, will determine the potential of success for all the scientists in the entire Program Project.

临床移植中心核心将由 10 个主要学术移植中心组成 美国每年总共进行大约 1360 例成人肾移植手术。其活动 将通过临床数据库、该计划与三个科学项目整合 项目网站、年度科学会议以及 10 个临床部门之间积极的临时互动 研究人员和主要研究人员。我们此核心的重点目标是提供 使用必要的患者材料和相关临床数据进行项目，以测试以下假设： 1) PBL 和肾移植活检中的基因表达和蛋白质组特征 确定与活检证实的急性排斥反应和慢性同种异体移植肾病相关，2) 基因和蛋白质表达谱将提供对所涉及的分子途径的见解 宿主免疫反应和供体器官对移植的反应，3) 充分性 免疫抑制的定义为缺乏排斥相关基因和蛋白质表达 可以在任何给定时间通过基因和蛋白质表达谱来确定，4) 靶向 SNP 基因分型和候选基因序列研究将确定基因之间的联系 与移植事件和结果以及基因相关的供体和受体 和蛋白质表达特征。综合所有这些假设，我们建议检验 种族（白种人、非裔美国人和西班牙裔）和/或性别在遗传上的可能性 影响移植后表达的至少一部分基因和蛋白质，并与临床相关 结果。关键的一点是患者亚组的正确临床名称和 成功完成注册和标本采集，这是该核心的两项主要任务， 将决定整个计划项目中所有科学家成功的潜力。