The Role of Endothelin-1 in Sickle Cell Disease

描述(由申请人提供)： 佐治亚健康科学大学的镰刀细胞中心在血红蛋白疾病研究方面有着悠久的卓越历史，特别是在镰状细胞疾病领域。这一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批杰出研究人员。这个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、肺和肾脏损伤以及疼痛的作用；2)培训镰状细胞疾病多学科研究活动的新研究人员，并通过暑期学生项目提高高中生的研究兴趣；3)为通过该计划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 专家们已经聚集在一起，确定内皮素-1在SC中的作用。将在SCD转基因小鼠模型中研究内皮素-1在血管病变、炎症、器官损伤以及疼痛和伤害性感觉发病机制中的作用。在该项目的第4年和第5年，将启动一项小型先导性临床试验，以研究ETA受体阻滞剂对炎症、疼痛、伤害性感觉和镰状肾病进展的安全性和有效性，以及对成年SCD患者的微血管血流和肺动脉循环的影响。翻译研究技能发展核心将培训早期研究人员如何进行高影响的、多学科的、翻译的、血红蛋白病研究。这一核心还将培训学者撰写有竞争力的K或ROI拨款，以支持向独立翻译研究职业的过渡。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。

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.