Rahima Zennadi, PhD

Associate Professor in Medicine
Associate Professor in Pathology
Campus mail 337MED Sci Res Bldg, Durham, NC 27710
Phone (919) 684-5378
Email address zenna001@mc.duke.edu

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.

Malaria

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

Publications

Zennadi, R., B. J. Moeller, M. W. Dewhirst, and M. J. Telen. “Role of LW and AKAP79 in beta-adrenergic receptor signaling-induced sickle red blood cell adhesion..” In Blood, 106:889A-889A. AMER SOC HEMATOLOGY, 2005.

Scholars@Duke

Zennadi, Rahima, Patrick C. Hines, Laura M. De Castro, Jean-Pierre Cartron, Leslie V. Parise, and Marilyn J. Telen. “Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-alphavbeta3 interactions..” Blood 104, no. 12 (December 1, 2004): 3774–81. https://doi.org/10.1182/blood-2004-01-0042.

PMID
15308566
Full Text

Eyler, C. E., T. L. Jackson, L. M. De Castro, R. Zennadi, J. M. Vance, A. Ashley-Koch, and M. J. Telen. “Effects of single nucleotide polymorphisms of the beta(2) adrenergic receptor and of adenylate cyclase on sickle red cell adhesion to laminin.” In Blood, 104:969A-970A. AMER SOC HEMATOLOGY, 2004.

Scholars@Duke

Zennadi, R., B. J. Moeller, E. J. Whalen, M. W. Dewhirst, and M. J. Telen. “Epinephrine-induced sickle red cell adhesion and vaso-occlusion in vivo is inhibited by the beta-adrenoceptor blocker propranolol.” In Blood, 104:107A-107A. AMER SOC HEMATOLOGY, 2004.

Scholars@Duke

Zennadi, R., E. J. Whalen, and M. J. Telen. “Protein kinases associated with activation of sickle red blood cell adhesion.” In Blood, 104:970A-970A. AMER SOC HEMATOLOGY, 2004.

Scholars@Duke

Zennadi, R., B. J. Moeller, Q. Zen, M. W. Dewhirst, and M. J. Telen. “In vitro exposure to epinephrine causes in vivo adhesion of human sickle red blood cells to vascular endothelium in nude mice: A new model for studying vaso-occlusion..” In Blood, 102:261A-261A. AMER SOC HEMATOLOGY, 2003.

Scholars@Duke

Zennadi, R., J. P. Cartron, and M. J. Telen. “cAMP-dependent activation of sickle red blood cell adhesion is associated with LW serine and tyrosine phosphorylation..” In Blood, 102:263A-263A. AMER SOC HEMATOLOGY, 2003.

Scholars@Duke

Zennadi, R., P. M. Hines, L. M. De Castro, J. P. Cartron, L. V. Parise, and M. J. Telen. “Modulation by epinephrine of PKA-dependent signaling pathways in sickle red blood cells induces activation of LW binding to endothelial cell alpha v beta 3 integrin..” In Blood, 100:118A-118A. AMER SOC HEMATOLOGY, 2002.

Scholars@Duke

Qin, Z., J. Cho, R. E. Lekwauwa, R. Zennadi, and M. J. Telen. “B-CAM/LU mediates laminin-independent cell-cell adhesion under both static and flow conditions..” In Blood, 100:451A-451A. AMER SOC HEMATOLOGY, 2002.

Scholars@Duke

Zennadi, R., and M. J. Telen. “Red cell signaling pathways cause increased sickle cell adhesion to non-activated endothelial cells..” Blood 98, no. 11 (November 16, 2001): 484A-484A.

Scholars@Duke

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