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., 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

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

Zennadi, R., Z. Abdel-Wahab, H. F. Seigler, and T. L. Darrow. “Generation of melanoma-specific, cytotoxic CD4(+) T helper 2 cells: requirement of both HLA-DR15 and Fas antigens on melanomas for their lysis by Th2 cells..” Cell Immunol 210, no. 2 (June 15, 2001): 96–105. https://doi.org/10.1006/cimm.2001.1809.

PMID
11520076
Full Text

Böhm, C. M., M. C. Mulder, R. Zennadi, M. Notter, A. Schmitt-Gräff, O. J. Finn, J. Taylor-Papadimitriou, et al. “Carbohydrate recognition on MUC1-expressing targets enhances cytotoxicity of a T cell subpopulation..” Scand J Immunol 46, no. 1 (July 1997): 27–34. https://doi.org/10.1046/j.1365-3083.1996.d01-91.x.

PMID
9246205
Full Text

Perrin, P., C. Burg, C. El Kouri, Y. Patry, R. Zennadi, E. Cassagnau, J. Le Pendu, J. Y. Douillard, and K. Meflah. “Interleukin-2 and sodium butyrate: An efficient combination for immunotherapy of rat colon cancer peritoneal carcinomatosis.” In Bulletin Du Cancer, 81:954–56, 1994.

Scholars@Duke

Perrin, P., C. Burg, C. E. Kouri, Y. Patry, R. Zennadi, E. Cassagnau, J. L. Pendu, J. Y. Douillard, and K. Meflah. “Interleukin-2 and sodium butyrate: An efficient combination for immunotherapy of rat colon cancer peritoneal carcinomatosis.” Bulletin Du Cancer 81, no. 11 (1994): 954–56.

Scholars@Duke

Zennadi, R., M. H. Blottière, C. Burg, J. Le Pendu, and J. Y. Douillard. “Failure of monoclonal antibodies against tumor associated antigens to improve tumor targeting of LAK cells in a model of rat colon carcinoma..” Bull Cancer 80, no. 8 (August 1993): 674–79.

PMID
8204947
Scholars@Duke

Ringeard, S., R. Zennadi, C. Goupille, M. Breimer, J. Harb, and J. LePendu. “S12.11 Involvement of histo-blood group antigens in the susceptibility of colon carcinoma cells to natural killer-mediated cytotoxicity.” Glycoconjugate Journal 10, no. 4 (August 1993): 298–298. https://doi.org/10.1007/bf01210045.

Full Text

Blottière, H. M., R. Zennadi, M. Grégoire, G. Aillet, M. G. Denis, K. Meflah, and J. Le Pendu. “Analysis of the relationship between stage of differentiation and NK/LAK susceptibility of colon carcinoma cells..” Int J Cancer 53, no. 3 (February 1, 1993): 409–17. https://doi.org/10.1002/ijc.2910530311.

PMID
8428794
Full Text

Labarrière, N., J. P. Piau, R. Zennadi, P. Blanchardie, M. Denis, and P. Lustenberger. “2) fucosyltransferase activity and sensitivity of tumor cells to LAK-mediated cytotoxicity..” In Vitro Cell Dev Biol 29A, no. 2 (February 1993): 140–44. https://doi.org/10.1007/bf02630945.

PMID
8473271
Full Text

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