The Role of Endothelin-1 in Sickle Cell Disease

Endothelin-1 在镰状细胞病中的作用

• 批准号: 8722606
• 负责人: Abdullah Kutlar
• 金额: $ 159.76万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8722606
• 关键词: Adult; Albuminuria; Area; Basic Science; Blood Circulation; Blood flow; Childhood; Clinical; Clinical Sciences; Clinical Trials; Development; Development Plans; Education; Endothelin; Endothelin-1; Functional disorder; Funding; Funding Opportunities; Goals; Grant; Health Sciences; Hematological Disease; Hemoglobinopathies; High School Student; Hypoxia; Inflammation; Informatics; Inherited; Injury; Interdisciplinary Study; Kidney; Kidney Diseases; Knowledge; Laboratories; Lung; Mentors; Nociception; Nociceptors; Organ; Pain; Pain Research; Pathogenesis; Patients; Peripheral; Preparation; Problem Solving; Recording of previous events; Renal function; Research; Research Activity; Research Infrastructure; Research Personnel; Research Project Grants; Research Training; Role; Sickle Cell; Sickle Cell Anemia; Staging; Students; Testing; Training; Training Programs; Transgenic Mice; Translational Research; Universities; Vascular Diseases; Writing; career; career development; chronic pain; experience; improved; interest; mouse model; multidisciplinary; programs; receptor; safety study; sickling; skills; social science research

DESCRIPTION (provided by applicant): The Sickle Cell Center at Georgia Health Sciences University has a long-standing history of excellence in hemoglobinopathies research, particularly in the area of sickle cell disease. This funding opportunity brings together a group of distinguished researchers in the fields of sickle cell disease (basic, clinical, and translational), endothelin, basic research in kidney disease, studies in a mouse model of sickle cell disease (SCD), and pain research. The goal of this project is tripartite: 1) To study the role of endothelin-1 in SCD with regards to inflammation, vasculopathy, lung and kidney injury, and pain; 2) To train new investigators in multidisciplinary research activities in sickle cell disease and promote research interest in high school students through a summer student program; 3) To provide administrative and informatics infrastructure for the centers funded through this initiative. To achieve these goals, a multidisciplinary team of experts has been assembled to identify the role of endothelin-1 in SC. The role of endothelin-1 in the pathogenesis of vasculopathy, inflammation, organ damage, and pain and nociception will be studied in a transgenic mouse model of SCD. In Years 4 and 5 of this project, a small pilot clinical trial will be initiated to study safety and efficacy of an ETA receptor blockade on inflammation, pain, nociception, and the progression of sickle nephropathy and on microvascular blood flow and pulmonary arterial circulation in adults with SCD. The Translational Research Skills Development Core will train early stage investigators how to conduct high impact, multidisciplinary, translational, hemoglobinopathy research. This core will also train scholars to write competitive K or ROI grants to support transition to independent translational research careers. The Administrative Coordinating Center will provide support for the administrative and coordinating activities and create and maintain the informatics infrastructure necessary to support the activities of the EHRA program.

描述（由申请人提供）： 格鲁吉亚健康科学大学的镰状细胞中心在血红蛋白病研究方面有着悠久的历史，特别是在镰状细胞病领域。这个资助机会汇集了镰状细胞病（基础，临床和翻译），内皮素，肾脏疾病基础研究，镰状细胞病（SCD）小鼠模型研究和疼痛研究领域的一组杰出研究人员。该项目的目标是三方面的：1）研究内皮素-1在SCD中与炎症、血管病变、肺和肾损伤以及疼痛有关的作用; 2）通过暑期学生计划培训新的研究人员参与镰状细胞病的多学科研究活动，并提高高中生的研究兴趣; 3）为通过该倡议资助的中心提供行政和信息基础设施。为了实现这些目标，一个多学科的团队， 将在SCD的转基因小鼠模型中研究内皮素-1在血管病变、炎症、器官损伤、疼痛和伤害感受的发病机制中的作用。在该项目的第4年和第5年，将启动一项小型试点临床试验，以研究ETA受体阻滞剂对炎症、疼痛、伤害感受和镰状肾病进展以及对SCD成人微血管血流和肺动脉循环的安全性和有效性。转化研究技能发展核心将培训早期研究人员如何进行高影响力，多学科，转化，血红蛋白病研究。该核心还将培训学者撰写具有竞争力的K或ROI赠款，以支持过渡到独立的翻译研究职业。行政协调中心将为行政和协调活动提供支持，并创建和维护必要的信息基础设施，以支持EHRA计划的活动。