NORTHERN CALIFORNIA COMPREHENSIVE SICKLE CELL CENTER

北加州综合镰刀细胞中心的目标 (NCCSCC)是1)在以下地点赞助和促进血红蛋白病研究 基础水平和临床水平；2)提供血红蛋白病 检测、咨询和教育受影响的人群 最现代的方法。为达致这些目标，我们成立了一个 儿童医院核心血红蛋白结构与诊断实验室 奥克兰研究所(CHORI)和 西湾(加州大学旧金山分校/旧金山综合医院)和东湾 (奥克兰儿童医院、高地医院)。这些计划提供 血红蛋白病检测、咨询和教育以及稳定、 由500多名镰状细胞病患者组成的具有良好特征的小组 (SCD)参与NCCSCC研究项目的人员。临床研究 项目旨在a)测试核心解压在 无菌性骨坏死的处理，b)看看是否急剧上升 血清分泌型磷脂酶AD预示急性胸部综合征 证明早期治疗干预是合理的，以及3)评估 潜在的新疗法(羟基脲、苯丁酸酯或克霉唑， 异丁酰胺、口服镁、口服螯合和各种形式的茎 细胞移植)。更多基础细胞和分子生物学研究 项目将a)开发我们新开发的SCD转基因小鼠模型 (它完全没有鼠标珠蛋白链)来探索 SC的病理生理学和评估潜在的新治疗方法，b)采用 全基因组扫描以确定未与珠蛋白簇连锁的基因 改变近交系SCD严重程度和珠蛋白链切换的基因 小鼠，c)使用人类b珠蛋白yac特异性转基因小鼠模型 定义顺式作用调控序列的作用，引导组织-和 人类b珠蛋白基因家族的阶段特异性表达，以及d) 建立一个合作研究项目，探索 补体、凝血酶和其他激动剂对镰状红细胞黏附的影响 血管内皮细胞，最终目标是确定一个潜在的作用 在镰刀状血管闭塞中的这些相互作用。这些项目将是 在CHORI的两个核心临床设施和位于 加州大学旧金山分校和劳伦斯·伯克利国家实验室。计划将是 由中心工作人员协调，由内部和外部评估 审查机构。

The objectives of the Northern California Comprehensive Sickle Cell Center (NCCSCC) are 1) to sponsor and facilitate hemoglobinopathy research at both fundamental and clinical levels and 2) to provide hemoglobinopathy detection, counseling, and education to affected populations using the most modern methods. To pursue these objectives, we have established a CORE hemoglobin structure and diagnosis laboratory at Childrens' Hospital Oakland Research Institute (CHORI) and CORE clinical research programs in the West Bay (UCSF/San Francisco General Hospital) and in the East Bay (Childrens' Hospital Oakland, Highland Hospital). These programs provide hemoglobinopathy detection, counseling and education as well as a stable, well characterized group of over 500 patients with sickle cell disease (SCD) who participate in NCCSCC research projects. Clinical research projects aim to a) test the efficacy of core decompression in the management of aseptic necrosis of bone, b) see whether an acute rise in serum secretory phospholipase AD heralds the acute chest syndrome and justifies early therapeutic intervention, and 3) evaluate the efficacy of potential new therapies (hydroxyurea + phenyl butyrate or clotrimazole, isobutyramide, oral magnesium, oral chelation and various forms of stem cell transplantation). More basic cell and molecular biology research projects will a) exploit our newly developed transgenic mouse model of SCD (which completely lacks mouse globin chains) to explore the pathophysiology of SC and evaluate potential new treatments, b) employ a genome a genome-wide scan to identify genes unlinked to the globin cluster that alter SCD severity and globin chain switching in inbred strains of mice, c) use a human b globin YAC specific transgenic mouse model to define the role of cis-acting regulatory sequences that direct tissue-and stage-specific expression of the human b globin gene family, and d) establish a collaborative research venture to explore the effects of complement, thrombin, and other agonists on the adherence of sickle RBC to vascular endothelium with the ultimate goal of defining a potential role for these interactions in sickle vaso-occlusion. These projects will be carried out at the 2 CORE clinical facilities, CHORI, and laboratories at UCSF and Lawrence Berkeley National Laboratory. Programs will be coordinated by Center staff and evaluated by both internal and external review bodies.