Boston Comprehensive Sickle Cell Center

描述(由申请人提供)：波士顿综合镰刀细胞中心(BCSCC)在过去六年中进行了重大重组。在这一竞争性续签申请中，在核心中心领导地位保持不变的情况下，我们选择通过在方向上做出重大改变来加强BCSCC可用的调查人员的优势。我们坚持认为，个别研究人员项目仍然是BCSCC使命的关键部分，因此为BCSCC带来了新的研究人员，重新调整了我们的工作台和临床研究活动的重点，包括患者服务研究、胎儿血红蛋白(HBF)诱导的翻译研究，进一步了解红细胞密度调节的遗传基础，并研究葡萄糖-6-磷酸脱氢酶(G6PD)的作用和内皮活性的调节。我们能够在目前的预算限制下做到这一点，是因为我们所有的项目调查员都有独立的R01或同等的支持，这为建立中心活动提供了重要的基础设施。我们还将在过去为合作临床试验招募患者方面的成功基础上再接再厉，我们建议进行一项旨在预防维生素D缺乏症及其引发的骨病的临床试验。 具体目标：1.通过召集大量临床核心患者作为I期和II期临床试验的候选者，对镰状细胞性贫血和HBSC病进行新的治疗试验2.进行以下创新研究：镰状红细胞水化的遗传决定因素；内皮功能和G6PD缺乏；新型口服制剂诱导HBF；改善对镰状细胞疾病儿童的全面预防服务；通过维生素D和钙治疗改善骨骼健康3.为所有BCSCC患者提供高质量的临床护理，为患者提供教育和咨询，为医疗专业人员提供教育和研究培训，并对血红蛋白疾病进行基因测试4.将BCSCC的组成部分整合到一个具有凝聚力的系统中，以提高其有效性，超越其单个项目的总和，鼓励与其他地区和国家镰状细胞中心的互动。

DESCRIPTION (provided by applicant): The Boston Comprehensive Sickle Cell Center (BCSCC) saw major reorganization over the past six years. In this competitive renewal application, while core center leadership remains unchanged, we have elected to build on the strengths of investigators available to BCSCC by making major changes in direction. We maintain the belief that individual investigator projects remain a critical part of the BCSCC mission and therefore have brought new investigators into the BCSCC, refocusing our bench and clinical research activities to include patient services research, translational studies of fetal hemoglobin (HbF) induction, further our understanding the genetic basis of red cell density regulation and examine the role of glucose-6-phosphate dehydrogenase (G6PD) and the modulation of endothelial activity. We are able to do this under current budget restaints because all of our project investigator have independent R01 or equivalent support that provides an important infrastructure upon which to build center activities. We will also build on our past successes in patient recruitment for collaborative clinical trials and we propose a clinical trial aimed at the prevention of hypovitaminosis D and its resulting bone disease. Specific Aims: 1. Carry out novel therapeutic trials in sickle cell anemia and HbSC disease by assembling a large Clinical Core of patients as candidates for Phase I and II clinical trials 2. Conduct innovative studies of: the genetic determinants of sickle erythrocyte hydration; endothelial function and G6PD deficiency; HbF induction by a novel oral agent; improving the delivery of comprehensive preventive services for children with sickle cell disease; and, improving bone health with vitamin D and calcium treatment 3. Provide high quality clinical care for all BCSCC patients with education and counseling for patients, education and research training for medical professionals and genetic testing for hemoglobinopathies 4. Meld the components of the BCSCC into a cohesive system to increase its effectiveness beyond the sum of its individual projects, encouraging interactions with other regional and national sickle cell centers.