Sickle Cell Disease
My research investigations in Hematology address the disorders associated with abnormalities affecting cell membrane proteins involved in cell-cell interactions and their role in sickle cell vasculopathy. In sickle cell disease (SCD), recurrent obstruction of the microvasculature leads to serious life-threatening complications such as acute pain crises, acute chest syndrome, kidney failure and cerebrovascular accidents triggered by ischemic injury in multiple organs. Vascular occlusion is caused largely by adherence of sickle red blood cells and leukocytes to the vascular endothelium. Prevention and reversal of established vascular occlusion in sickle cell patients are still a therapeutic challenge. We are testing the hypothesis that vascular occlusion-dependent leukocyte and endothelial cell (EC) activation and inflammation leads to the increased ischemic oxidative stress and subsequent oxidative tissue injury. We propose that generation of ischemic oxidative stress, via activation of various abnormal signaling mechanisms, creates a positive feed-back loop that further enhances vaso-occlusion, endothelial activation and inflammation in the vasculature in general, and in particular, in the brain, kidney and lung vessels. We believe that targeting these signaling mechanisms will not only have anti-vaso-occlusive effects, but may also reduce inflammation and ischemic oxidative stress-induced endothelial dysfunction. In addition, we are also investigating signaling mechanisms activated by stress erythropoiesis during erythroid cell proliferation and maturation in sickle cell disease.
Up to 15 to 20% of patients with falciparum malaria die despite our best malaria treatments. We clearly need more effective treatments than current anti-malarial drugs alone provide. Adherence of Plasmodium falciparum-infected red blood cells is at the core of the pathophysiology of severe malaria, and could lead to abnormal endothelial function, a process also central to the pathology of severe malaria. Using unique set of pharmacologic tools we are trying to elucidate the signaling mechanisms leading to infected red cell adherence to the vascular endothelium and the effects of these mechanisms on the vascular endothelium, and how best to target the parasite Plasmodium falciparum for treatment of malaria.
Education and Training
- Ph.D., University of Nantes (France), 1992
- M.S., University of Nantes (France), 1989