COMPREHENSIVE SICKLE CELL CENTER

综合性镰状细胞中心

• 批准号: 7246531
• 负责人: Cage S Johnson
• 金额: $ 131.14万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7246531
• 关键词: COMPREHENSIVE; SICKLE; CELL; CENTER

The Comprehensive Sickle Cell Center (CSCC) at the Los Angeles County+USC Medical Center: represents the continued collaboration of an investigative group that has devoted a substantial portion of their careers since 1972 towards basic, applied, and clinical research in sickle cell disease. The overall focus and unifying theme of this research continues to be the pathophysiology, clinical consequences and treatment of vascular events in sickle cell disease. Vascular disorders, including vascular occlusion, represent the most important cause of morbidity and mortality in this disease, yet their pathophysiology is still incompletely understood and their treatment remains Largely unsatisfactory. Determining possible genetic bases for the variable clinical severity of the disease and genetic approaches to therapy are also of central interest, yet again our understanding in these areas is less than satisfactory. In the current proposal, this group of investigators will continue to be concerned with vascular disorders in sickle cell disease; in addition, we have incorporated genetics-based components seeking to understand the variable clinical severity and to develop novel therapeutic approaches in this disease. The program described herein consists of five hypothesis-based projects (Projects 1-5), and three Cores (Clinical/Patient Service, Laboratory, Animal) that support these projects and the overall objectives of the Center. Project 1, our Collaborative Clinical Research Component, seeks to examine relations among polymorphisms in specific blood groups and clinical severity; Project 2 examines critical elements of the pathophysiology of pulmonary hypertension; Project 3 seeks to determine the ability of anti-inflammatory agents to block hypoxia-induced decreases of blood flow; Project 4 explores genetic therapy for sickle cell disease via examining the potential benefits of self-inactivating lentiviral vectors; Project 5 seeks to define in detail the molecular mechanisms that lead to the accumulation of monocytes and PMN in the alveolar compartment. We strongly support the Inter-Center Collaborative concept and the Sickle Cell Scholar program, and believe that successful completion of our Projects will yield important new information for improved patient care.

洛杉矶县+USC医疗中心的综合镰状细胞中心（CSCC）： 自1972年以来，该组织的持续合作一直致力于其职业生涯的很大一部分，用于镰状细胞疾病的基本，应用和临床研究。这项研究的总体重点和统一主题仍然是镰状细胞病中血管事件的病理生理学，临床后果和治疗。血管疾病，包括血管阻塞，代表了这种疾病中发病和死亡率的最重要原因，但其病理生理学仍然尚不完全了解，并且它们的治疗在很大程度上不令人满意。确定疾病可变临床严重程度和治疗遗传学方法的可能遗传基础也具有核心利益，但我们在这些地区的理解又不令人满意。在当前的提案中，这组研究人员将继续关注镰状细胞疾病中的血管疾病。此外，我们还纳入了旨在了解可变临床严重程度并开发这种疾病中新型治疗方法的基于遗传学的组件。本文所述的计划由五个基于假设的项目（项目1-5）和支持这些项目和中心的整体目标的三个核心（临床/患者服务，实验室，动物）组成。我们的协作临床研究组成部分项目1试图检查特定血型和临床严重程度的多态性之间的关系；项目2研究了肺动脉高压病理生理学的关键元素；项目3旨在确定抗炎药阻断缺氧引起的血液流量减少的能力；项目4通过检查慢病毒载体的潜在益处来探索镰状细胞疾病的基因疗法；项目5旨在详细定义导致单核细胞和PMN积累的分子机制。我们强烈支持中心间的协作概念和镰状细胞学者计划，并认为成功完成我们的项目将产生重要的新信息，以改善患者护理。