Clinicians have long been aware that not all patients with sickle cell anemia follow the same clinical course despite the fact that they all have the identical genetic abnormality. Some are more anemic than others, the frequency of vaso-occlusive events vary, and life expectancy differs. There are several reasons why the red blood cell (RBC) membrane is likely to be one of the most important modulators of clinical severity. First, it is the structure most intimately associated with HbS, and is therefore vulnerable to damage by its prodding and noxious byproducts. Second, it influences the concentration of HbS in the cell. And third, the membrane is the face of the cell that is recognized by proteins and cells in the blood, along the vasculature, and in the reticuloendothelium. In this proposal we focus on two main areas: (1) studying the abnormal membrane protein interactions of sickle cells - those involving ankyrin and protein 3, and (2) cloning and characterizing a membrane protein(s) that influence(s) the concentration of hemoglobin in the cell - the water channel.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Comprehensive Center (P60)
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Boston Medical Center
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