NORTHERN CALIFORNIA COMPREHENSIVE SICKLE CELL CENTER

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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.