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

Böhm, CM, Mulder, MC, Zennadi, R, Notter, M, Schmitt-Gräff, A, Finn, OJ, Taylor-Papadimitriou, J, Stein, H, Clausen, H, Riecken, EO, and Hanski, C. "Carbohydrate recognition on MUC1-expressing targets enhances cytotoxicity of a T cell subpopulation." Scand J Immunol 46, no. 1 (July 1997): 27-34.

PMID
9246205
Scholars@Duke

Perrin, P, Burg, C, El Kouri, C, Patry, Y, Zennadi, R, Cassagnau, E, Le Pendu, J, Douillard, JY, and Meflah, K. "Interleukin-2 and sodium butyrate: An efficient combination for immunotherapy of rat colon cancer peritoneal carcinomatosis." January 1, 1994.

Scholars@Duke

Perrin, P, Burg, C, Kouri, CE, Patry, Y, Zennadi, R, Cassagnau, E, Pendu, JL, Douillard, JY, and Meflah, K. "Interleukin-2 and sodium butyrate: An efficient combination for immunotherapy of rat colon cancer peritoneal carcinomatosis." Bulletin du Cancer 81, no. 11 (1994): 954-956.

Scholars@Duke

Zennadi, R, Blottière, MH, Burg, C, Le Pendu, J, and Douillard, JY. "Failure of monoclonal antibodies against tumor associated antigens to improve tumor targeting of LAK cells in a model of rat colon carcinoma." Bulletin Du Cancer 80, no. 8 (August 1993): 674-679.

PMID
8204947
Scholars@Duke

Ringeard, S, Zennadi, R, Goupille, C, Breimer, M, Harb, J, and LePendu, J. "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.

Full Text

Blottière, HM, Zennadi, R, Grégoire, M, Aillet, G, Denis, MG, Meflah, K, and Le Pendu, J. "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): 409-417.

PMID
8428794
Scholars@Duke

Labarriere, N, Piau, JP, Zennadi, R, Blanchardie, P, Denis, M, and Lustenberger, P. "Retinoic acid modulation of α(1→2) fucosyltransferase activity and sensitivity of tumor cells to LAK-mediated cytotoxicity." In Vitro Cellular &Amp; Developmental Biology Animal 29, no. 2 (February 1, 1993): 140-144.

Full Text

Labarrière, N, Piau, JP, Zennadi, R, Blanchardie, P, Denis, M, and Lustenberger, P. 2) fucosyltransferase activity and sensitivity of tumor cells to LAK-mediated cytotoxicity." In Vitro Cell Dev Biol 29A, no. 2 (February 1993): 140-144.

PMID
8473271
Scholars@Duke

LABARRIERE, N, PIAU, JP, ZENNADI, R, BLANCHARDIE, P, DENIS, M, and LUSTENBERGER, P. "RETINOIC ACID MODULATION OF ALPHA(1-]2) FUCOSYL-TRANSFERASE ACTIVITY AND SENSITIVITY OF TUMOR-CELLS TO LAK-MEDIATED CYTOTOXICITY." IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL 29, no. 2 (February 1993): 140-144.

Scholars@Duke

Zennadi, R, Garrigue, L, Ringeard, S, Ménoret, A, Blanchardie, P, and Le Pendu, J. "Analysis of factors associated with the tumorigenic potential of 12 tumor clones derived from a single rat colon adenocarcinoma." International Journal of Cancer 52, no. 6 (December 1992): 934-940.

PMID
1459734
Full Text

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