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

Schwartz, EA, and Zennadi, R. "Proteomic Analysis of ERK1/2-Mediated Human Sickle Red Blood Cell Membrane Protein Phosphorylation." November 16, 2012.

Scholars@Duke

Zennadi, R. "Therapeutic Benefit of Small Molecule Inhibitors of MEK/ERK in Reducing Sickle Red Cell Adhesion and Vaso-Occlusion in Vivo." November 16, 2012.

Scholars@Duke

Zennadi, R. "Therapeutic Benefit of Small Molecule Inhibitors of MEK/ERK in Reducing Sickle Red Cell Adhesion and Vaso-Occlusion in Vivo." November 16, 2012.

Scholars@Duke

Zennadi, R, McMahon, T, and Telen, M. "Nitric oxide deficiency in sickle red cells is associated with increased cell adhesion to endothelium and vaso-occlusion.": Elsevier BV, July 2012.

Full Text

Zennadi, R, Whalen, EJ, Soderblom, EJ, Alexander, SC, Thompson, JW, Dubois, LG, Moseley, MA, and Telen, MJ. "Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium." Blood 119, no. 5 (February 2012): 1217-1227.

PMID
22147898
Full Text

Boateng, LA, Zennadi, R, and Telen, MJ. "Sickle Red Blood Cell Induced Adhesion of Neutrophils to Endothelial Cells and Biologic Correlates of Leukocyte Activation." November 18, 2011.

Scholars@Duke

Zhu, H, Zennadi, R, Xu, BX, Eu, JP, Torok, JA, Telen, MJ, and McMahon, TJ. "Impaired adenosine-5'-triphosphate release from red blood cells promotes their adhesion to endothelial cells: a mechanism of hypoxemia after transfusion." Critical Care Medicine 39, no. 11 (November 2011): 2478-2486.

PMID
21765360
Full Text

Burnette, AD, Nimjee, SM, Batchvarova, M, Zennadi, R, Telen, MJ, Nishimura, J-I, and Sullenger, BA. "RNA aptamer therapy for vaso-occlusion in sickle cell disease." Nucleic Acid Ther 21, no. 4 (August 2011): 275-283.

PMID
21793788
Full Text

Zhu, H, Zennadi, R, Xu, B, Eu, JP, Torok, J, Telen, MJ, and McMahon, TJ. "Red Blood Cell Release Of ATP Prevents Endothelial Adhesion: Implications For Post-Transfusion Lung Dysfunction." AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 183 (2011).

Scholars@Duke

Zennadi, R, and Telen, MJ. "Atypical Activation of Plasma Membrane-Bound ERK1/2 Is Associated with Regulation of Sickle Red Cell Adhesion to Endothelium." November 19, 2010.

Scholars@Duke

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