Rahima Zennadi, PhD

Associate Professor in Medicine
Associate Professor in Pathology
Campus mail 337MED Sci Res Bldg, Durham, NC 27710
Phone (919) 684-2135
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

Wang, Qinhong, and Rahima Zennadi. “The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications.” Antioxidants (Basel) 10, no. 10 (October 13, 2021). https://doi.org/10.3390/antiox10101608.

PMID
34679742
Full Text

Thamilarasan, Madhan, William E. Fogler, John L. Magnani, and Rahima Zennadi. “Restoration of Normal Blood Flow in Mouse Models of Sickle Cell Vaso-Occlusion Following Intravenous or Subcutaneous Administration of a Highly Potent E-Selectin Specific Inhibitor.” In Blood, 136:17–17. American Society of Hematology, 2020. https://doi.org/10.1182/blood-2020-140276.

Full Text

Wang, Qinhong, and Rahima Zennadi. “Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis.” Int J Mol Sci 21, no. 12 (June 15, 2020). https://doi.org/10.3390/ijms21124259.

PMID
32549393
Full Text

Thamilarasan, Madhan, Rodolfo Estupinan, Ines Batinic-Haberle, and Rahima Zennadi. “Mn porphyrins as a novel treatment targeting sickle cell NOXs to reverse and prevent acute vaso-occlusion in vivo.” Blood Adv 4, no. 11 (June 9, 2020): 2372–86. https://doi.org/10.1182/bloodadvances.2020001642.

PMID
32479589
Full Text

Thamilarasan, Madhan, Rodolfo Estupinan, and Rahima Zennadi. “Mn Porphyrin-Based Redox Active Drugs Improve Anemia and Reduce Organ Damage in a Murine Model of Sickle Cell Disease.” In Blood, 134:2255–2255. American Society of Hematology, 2019. https://doi.org/10.1182/blood-2019-131140.

Full Text

McMahon, Timothy J., Siqing Shan, Daniel A. Riccio, Milena Batchvarova, Hongmei Zhu, Marilyn J. Telen, and Rahima Zennadi. “Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.” Blood Adv 3, no. 17 (September 10, 2019): 2586–97. https://doi.org/10.1182/bloodadvances.2019031633.

PMID
31484636
Full Text

MacKinney, Anson, Emily Woska, Ivan Spasojevic, Ines Batinic-Haberle, and Rahima Zennadi. “Disrupting the vicious cycle created by NOX activation in sickle erythrocytes exposed to hypoxia/reoxygenation prevents adhesion and vasoocclusion.” Redox Biol 25 (July 2019): 101097. https://doi.org/10.1016/j.redox.2019.101097.

PMID
30661992
Full Text

Madhan, Thamilarasan, Rodolfo Estupinan, and Rahima Zennadi. “Mn Porphyrin-Based Redox Active Drugs As Novel Anti-Adhesive and Anti-Inflammatory Agents Targeting Sickle Red Blood Cell Oxidative Damage In Vivo.” In Blood, 132:270–270. American Society of Hematology, 2018. https://doi.org/10.1182/blood-2018-99-119066.

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Telen, Marilyn J., Milena Batchvarova, Siqing Shan, Petra H. Bovee-Geurts, Rahima Zennadi, Anna Leitgeb, Roland Brock, and Maria Lindgren. “Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.” Br J Haematol 175, no. 5 (December 2016): 935–48. https://doi.org/10.1111/bjh.14303.

PMID
27549988
Full Text

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