Rahima Zennadi
Associate Professor in Medicine

My research in Hematology addresses three areas of investigation: disorders associated with sickle cell disease pathophysiology, venous thrombosis/thromboembolism (VT/E) associated with aging, and cerebrovascular injury.

In sickle cell disease, vaso-occlusion leads to serious life-threatening complications, including acute pain crises and irreversible organ damage.  Vaso-occlusion is caused largely by sickle red blood cell adhesion to the vascular endothelium.  Prevention of vaso-occlusion and reversal of ongoing vaso-occlusion in patients with sickle cell disease are still a therapeutic challenge.  My research focus is on disorders associated with abnormalities of molecular mechanisms affecting red blood cell signaling mechanisms affecting membrane proteins.  The goal of my research studies is (1) to characterize the signaling pathways involved in red blood cell interactions with the vascular endothelium and with leukocytes, with a particular emphasis on the role of small non-coding RNAs (snoRNAs) of the Rpl13a locus of the ribosomal protein Rpl13a, in regulating oxidative stress in sickle red cells leading to sickle cell pathogenesis and the associated downstream events; and (2) development of target-directed therapies for treatment of sickle cell vasculopathy.  

My research studies also include identification of the role of red cells in aging, the most significant risk factor for VT/E, and cognitive impairment, including two key pathologies, namely cerebrovascular disease and Alzheimer disease (AD).  These pathologies have been recognized long ago in the aging population.  In particular, my lab is investigating the mechanisms of action of the Rpl13a snoRNAs in red cells and their role in triggering activation of the coagulation cascade in mid-life stage adults, predisposing mid-life stage population with prominent oxidative stress to increased risks for development of VT/E.  Our research in addition, encompasses identification of the underlying RBC molecular aberrations involved in impairing blood-brain-barrier (BBB) integrity and increasing amyloid peptide deposition on the brain, responsible for the neurobiological changes observed following hemorrhagic strokes and in the AD brain, respectively.  Specifically, we are exploring the contribution of RBCs to triggering the removal of cilia (deciliation), a cellular organelle projecting from the endothelial cell surface into the CNS blood, which impacts BBB integrity. Further, we are investigating the redox-associated mechanisms in RBCs in old adults that affect the integrity of brain endothelial cilia and how deciliation by RBCs may accelerate amyloid precursor protein signaling, thus increasing the risk for AD development. 

Current Appointments & Affiliations

Contact Information

  • 337MED Sci Res Bldg, Durham, NC 27710
  • Duke Box 2615, Durham, NC 27710

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