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 develop innovative ways to provide hemoglobinopathy detection, counseling and education to affected populations. To pursue these objectives, we have established a CORE hemoglobinopathy laboratory and CORE clinical programs in the West Bay (UCSF-San Francisco General Hospital) and in the East Bay (Children's Hospital, Alta Bates Hospital, 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 are available to participate in NCCSCC research projects. These projects aim to: a) develop a transgenic mouse model of human (SCD), b) develop a model system for the targeted delivery of globin genes to erythroid cells, using tissues specific retroviral vectors; c) define sequences that direct stage and tissue specific expression of the beta globin gene family by introduction of yeast artificial chromosomes containing the intact human beta globin locus into murine erythroleukemia cells, embryonic stem cell, or mouse oocytes; d) see whether association of abnormal or unpaired hemoglobin chains with the red cell membrane influences membrane function in the sickle cell disorders; e) determine whether loss of complement regulatory proteins from sickle red cells affects their susceptibility to complement dependent injury and lysis; f) determine the etiology and factors determining the severity of the acute chest syndrome, g) evaluate the interaction between sickle cells and activated endothelial cells, and h) participate in clinical trials of various therapies for SCD (hydroxyurea, butyrate analogs, bone marrow transplantation, transfusions). We will also evaluate ketosolae analgesia for vaso-occlusive crises, correlate clinical and hematologic features of sCD with polymer formation in young children (<3 yrs), assess the impact of transfusion therapy on early cerebral vascular ischemia in SCD, and test the utility of adjuvant therapy with interferon gamma 1b in enhancing the response to pneumococcal vaccine in children with SCD. Psychosocial research projects will assess the efficacy of information transfer through translators and other issues relevant to cross-cultural counseling, the factors that determine acceptability to prenatal diagnosis and the impact of comprehensive education on the extended family of newly diagnosed infants with SCD. These projects will be carried out at the two CORE families as well as in laboratories at UCSF and UCB (Lawrence Berkeley Laboratories). Programs will be coordinated by Center staff and evaluated by both internal and external review bodies.
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