Developing novel biomarkers of renal transplant rejection

开发肾移植排斥反应的新型生物标志物

• 批准号: 10477329
• 负责人: Reza Abdi
• 金额: $ 15.22万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-06 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10477329
• 关键词: Acute; Affect; Allografting; Area; Award; B-Lymphocytes; Back; Biological Markers; Biopsy; Blood Platelets; Caliber; Cells; Chronic; Chronic rejection of renal transplant; Clinical; Collaborations; Complication; Country; Data; Development; Diagnosis; Diagnostic; Differential Diagnosis; End stage renal failure; Environment; Expression Profiling; Fostering; Genes; Genetic Polymorphism; Goals; Graft Rejection; Grant; Hospitals; Human; ITGB3 gene; Immune; Immunogenetics; Immunology; Incidence; Infrastructure; Injury; Innovative Therapy; Interdisciplinary Study; Kidney; Kidney Diseases; Kidney Transplantation; Learning; Longitudinal Studies; Malignant Neoplasms; Mediating; Mentors; Messenger RNA; Methods; Mid-Career Clinical Scientist Award (K24); Monitor; Morbidity - disease rate; Nature; Organ Donor; Organ Transplantation; Outcome; Outpatients; Pathogenesis; Patient risk; Patients; Prognosis; Protocols documentation; RNA; Recurrence; Research; Research Personnel; Research Proposals; Resources; Risk; Risk Assessment; Risk Factors; Role; Scientist; System; T-Lymphocyte; Testing; Therapeutic immunosuppression; Training; Translational Research; Transplant Recipients; Transplantation; Urine; Woman; allograft rejection; base; candidate marker; career; clinically significant; cost effective; design; diagnostic assay; exosome; experience; experimental study; high risk; improved outcome; individual patient; inflammatory milieu; innovation; interest; ischemic injury; isoimmunity; kidney allograft; medical schools; mortality; multidisciplinary; nanovesicle; new technology; next generation; noninvasive diagnosis; novel; novel marker; patient oriented; patient oriented research; personalized medicine; platelet function; predictive marker; prognostic; prognostic tool; programs; recruit; research clinical testing; skills; skills training; therapeutic target; tool; treatment choice; urinary; user-friendly

Project Summary/Abstract Renal transplantation has become the treatment of choice for patients with end-stage renal disease. However, acute renal allograft rejection (ARAR) remains a major complication after kidney transplantation and is associated with significant morbidity and mortality. Importantly, ARAR remains the strongest predictor of long-term renal allograft injury and survival. Currently known risk factors do not allow for the accurate assessment of ARAR risk. In addition, we currently lack a non-invasive, cost-effective clinical test to diagnose ARAR. The development of novel urinary exosomes represents promising prognostic tools for ARAR risk assessment. The goals of this Mid-Career Investigator Award are to expand Dr. Reza Abdi’s patient-oriented research program towards the development of better diagnostic and prognostic strategies for ARAR in renal transplant patients, further enhance Dr. Abdi’s mentoring skills, and provide him with the resources and support to foster the development of trainees interested in patient- oriented research in transplantation. This research proposal is built upon the candidate’s prior research identifying ARAR biomarkers in transplantation and is strengthened by his multidisciplinary collaborations. These projects offer a unique opportunity for mentees to train in patient-oriented clinical and translational transplantation research that is at the intersection of immunology, biomarker research and transplantation. From this training vehicle, mentees will gain skills to carry out patient-oriented research in transplantation, learn to apply cutting-edge exosome and mRNA profiling and analysis and gain hands-on experience in translational research in ARAR. The rich resources and infrastructure at Harvard Medical School and the Brigham and Women’s Hospital Renal Division/Transplantation Research Center provide an outstanding scientific research environment to train the next generation of researchers in transplantation. These studies will not only help identify novel immunogenetic biomarkers for predicting ARAR and help in the creation of a clinical tool for diagnosing ARAR, but will also advance our understanding of the pathogenesis of ARAR and greatly assist in the development of innovative therapies in renal transplantation.

项目摘要/摘要 肾移植已成为终末期肾脏患者的首选治疗方法 疾病。然而，急性肾脏同种异移植排斥（ARAR）仍然是主要的并发症 肾脏移植，与显着的发病率和死亡率有关。重要的是， ARAR仍然是长期肾脏合物损伤和生存的有力预测指标。现在 已知的风险因素不允许准确评估ARAR风险。另外，我们 目前缺乏无创，具有成本效益的临床测试来诊断ARAR。发展的发展 新型的尿外泌体代表了用于ARAR风险评估的有希望的预后工具。这 这个职业中期调查员奖的目标是扩大Reza Abdi博士的注重患者 为制定更好的诊断和预后策略的研究计划 在肾脏移植患者中的ARAR，进一步提高了Abdi博士的心理技能，并为他提供 有了资源和支持，以促进对患者感兴趣的受训者的发展 - 面向移植的研究。该研究建议是基于候选人的先验 研究识别Arar生物标志物在移植中的研究，并通过其增强 多学科合作。这些项目为Mentores提供了独特的机会训练 面向患者的临床和翻译移植研究 免疫学，生物标志物研究和移植。从这款训练工具中，受训者将 获得以患者为导向的移植研究的技能，学会应用尖端 外部和mRNA分析和分析并获得转化方面的动手经验 Arar的研究。哈佛医学院和 Brigham and妇女医院肾脏分区/移植研究中心提供了一个 杰出的科学研究环境，以培训下一代研究人员 移植。这些研究不仅将有助于确定新型免疫生物标志物 预测ARAR并帮助创建用于诊断ARAR的临床工具，但也将 促进我们对ARAR发病机理的理解，并大大帮助发展 肾移植中的创新疗法。