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: 10686193
• 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 2024-05-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686193
• 关键词: Acute; Affect; Allografting; Area; Award; B-Lymphocytes; Back; Biological Markers; Biopsy; Blood Platelets; Cells; Chronic; Chronic rejection of renal transplant; Clinical; Collaborations; Complication; Country; Data; Development; Diagnosis; Diagnostic; Diameter; 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; Malignant Neoplasms; Mediating; Mentors; Messenger RNA; Methods; Mid-Career Clinical Scientist Award (K24); Monitor; Morbidity - disease rate; Nature; Organ Donor; Organ Transplantation; Outcome; 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; 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; risk prediction; skills; 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.

项目概要/摘要 肾移植已成为终末期肾病患者的首选治疗方法 然而，急性肾同种异体移植排斥（ARAR）仍然是术后的主要并发症。 肾移植与显着的发病率和死亡率相关。 目前，ARAR 仍然是长期同种异体移植肾损伤和存活的最强预测因子。 已知的风险因素不允许准确评估 ARAR 风险。 目前缺乏一种非侵入性、经济有效的临床测试来诊断 ARAR。 新型尿液外泌体代表了 ARAR 风险评估的有前景的预后工具。 该中期职业研究员奖的目标是扩大 Reza Abdi 博士以患者为中心的 旨在制定更好的诊断和预后策略的研究计划 ARAR 在肾移植患者中的应用，进一步增强 Abdi 博士的指导技能，并为他提供 提供资源和支持，促进对患者感兴趣的学员的发展 该研究计划是建立在候选人先前的基础上的。 确定移植中 ARAR 生物标志物的研究并得到他的支持 这些项目为学员提供了独特的培训机会。 以患者为中心的临床和转化移植研究，处于交叉点 学员将通过该培训工具学习免疫学、生物标志物研究和移植。 获得在移植领域开展以患者为中心的研究的技能，学习应用尖端技术 外泌体和 mRNA 分析和分析，并获得转化方面的实践经验 哈佛医学院和 ARAR 的丰富资源和基础设施。 布莱根妇女医院肾脏科/移植研究中心提供 优良的科研环境，培养下一代研究人员 这些研究不仅有助于识别新的免疫遗传学生物标志物。 预测 ARAR 并帮助创建诊断 ARAR 的临床工具，但也将 我们对 ARAR 发病机制的了解进展并极大地协助了开发 肾移植的创新疗法。

项目成果

Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection.

• DOI: 10.1038/s42255-021-00407-6
• 发表时间: 2021-06
• 期刊: NATURE METABOLISM
• 影响因子: 20.8
• 作者: Montefusco, Laura;Ben Nasr, Moufida;D'Addio, Francesca;Loretelli, Cristian;Rossi, Antonio;Pastore, Ida;Daniele, Giuseppe;Abdelsalam, Ahmed;Maestroni, Anna;Dell'Acqua, Marco;Ippolito, Elio;Assi, Emma;Usuelli, Vera;Seelam, Andy Joe;Fiorina, Roberta Maria;Chebat, Enrica;Morpurgo, Paola;Lunati, Maria Elena;Bolla, Andrea Mario;Finzi, Giovanna;Abdi, Reza;Bonventre, Joseph V.;Rusconi, Stefano;Riva, Agostino;Corradi, Domenico;Santus, Pierachille;Nebuloni, Manuela;Folli, Franco;Zuccotti, Gian Vincenzo;Galli, Massimo;Fiorina, Paolo
• 通讯作者: Fiorina, Paolo

miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.

• DOI: 10.1111/ajt.16581
• 发表时间: 2021-10
• 期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
• 作者: Usuelli V;Ben Nasr M;D'Addio F;Liu K;Vergani A;El Essawy B;Yang J;Assi E;Uehara M;Rossi C;Solini A;Capobianco A;Rigamonti E;Potena L;Venturini M;Sabatino M;Bottarelli L;Ammirati E;Frigerio M;Castillo-Leon E;Maestroni A;Azzoni C;Loretelli C;Joe Seelam A;Tai AK;Pastore I;Becchi G;Corradi D;Visner GA;Zuccotti GV;Chau NB;Abdi R;Pezzolesi MG;Fiorina P
• 通讯作者: Fiorina P

Active targeted delivery of immune therapeutics to lymph nodes.

• DOI: 10.1097/mot.0000000000000495
• 发表时间: 2018-03
• 期刊: Current opinion in organ transplantation
• 影响因子: 2.2
• 作者: Bahmani B;Vohra I;Kamaly N;Abdi R
• 通讯作者: Abdi R

Association of Cold Ischemia Time With Acute Renal Transplant Rejection.

• DOI: 10.1097/tp.0000000000002106
• 发表时间: 2018-07
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Postalcioglu M;Kaze AD;Byun BC;Siedlecki A;Tullius SG;Milford EL;Paik JM;Abdi R
• 通讯作者: Abdi R