We have devoted significant attention in recent years to the role of sphingolipid metabolism in sickle red blood cells. We have recently identified a novel mechanism of feed-forward inflammatory signaling in SCD whereby sickled RBC membrane strain increases the activity of sphingomyelinase (SMase), which contributes to membrane lipid composition and budding of cellular vesicles. This dysregulation of sphingolipid metabolism leads to the aberrant production and release of cell-derived microparticles (SS MVs). MVs have been described as transcellular delivery vehicles that can transfer receptors, adhesion molecules, kinases, and lipids between cells. We are also investigating a potential pathogenic role of SS MVs in bone and joint disorders including osteonecrosis of the femoral head (ONFH). Read More