This proposal seeks to re-establish a Comprehensive Sickle Cell Center at the University of Southern California School of Medicine and its associated institutions. The focus of the research effort at this Center has been directed at the pathophysiology, clinical consequences and treatment of vascular occlusion in Sickle Cell Anemia and its variants. Vascular occlusion represents the most important cause of morbidity and mortality in this disease, yet its pathophysiology is still incompletely understood, and its treatment remains unsatisfactory. The present proposal centers its effort on our hypothesis that poorly deformable dense erythrocytes, abnormally adherent erythrocytes and poorly deformable neutrophils combine to initiate the cascade of events that ultimately lead to recurrent vascular obstruction, ischemia and infarction in this disease.
The specific aims of the proposal are: i) to develop an improved understanding of the pathophysiology of vascular occlusion in sickle cell disease and ii) to develop improved methods of preventing vascular occlusion in this disease. Project 1 seeks to further define the relationships between globin gene haplotypes and disease expression. Project 2 focuses on the molecular and biochemical mechanisms of RBC adherence to endothelium. Project 3 will study neutrophil physiology in this disease and its role in vaso-occlusion. Project 4 seeks to determine the effect of specific therapeutic maneuvers on the clinical course of cerebrovascular disease. Project 5 employs a novel strategy to define the beneficial effect of hydroxyurea in retarding the clinical progression of certain complications of the disease associated with poor prognosis. These 5 research projects are supported by 3 cores: data coordinating, adhesion laboratory, and hemorheology laboratory, which function to promote the overall research effort. This application has been developed to promote collaboration within our Center and, through projects 4 and 5, seeks collaboration with other Centers and supports the goals of the National Sickle Cell Disease Program.
| Rabai, M; Detterich, J A; Wenby, R B et al. (2014) Effects of ethanol on red blood cell rheological behavior. Clin Hemorheol Microcirc 56:87-99 |
| Castellini, Michael; Elsner, Robert; Baskurt, Oguz K et al. (2006) Blood rheology of Weddell seals and bowhead whales. Biorheology 43:57-69 |
| Johnson, Cage S (2005) Arterial blood pressure and hyperviscosity in sickle cell disease. Hematol Oncol Clin North Am 19:827-37, vi |
| Senturk, Umit K; Yalcin, Ozlem; Gunduz, Filiz et al. (2005) Effect of antioxidant vitamin treatment on the time course of hematological and hemorheological alterations after an exhausting exercise episode in human subjects. J Appl Physiol 98:1272-9 |
| Johnson, Cage S (2005) The acute chest syndrome. Hematol Oncol Clin North Am 19:857-79, vi-vii |
| Baskurt, Oguz K; Yalcin, Ozlem; Meiselman, Herbert J (2004) Hemorheology and vascular control mechanisms. Clin Hemorheol Microcirc 30:169-78 |
| Armstrong, J K; Wenby, R B; Meiselman, H J et al. (2004) The hydrodynamic radii of macromolecules and their effect on red blood cell aggregation. Biophys J 87:4259-70 |
| Baskurt, Oguz K; Yalcin, Ozlem; Ozdem, Sadi et al. (2004) Modulation of endothelial nitric oxide synthase expression by red blood cell aggregation. Am J Physiol Heart Circ Physiol 286:H222-9 |
| Batra, Sandeep; Perelman, Natalya; Luck, Lori R et al. (2003) Pediatric tumor cells express erythropoietin and a functional erythropoietin receptor that promotes angiogenesis and tumor cell survival. Lab Invest 83:1477-87 |
| Chong-Martinez, B; Buchanan, T A; Wenby, R B et al. (2003) Decreased red blood cell aggregation subsequent to improved glycaemic control in Type 2 diabetes mellitus. Diabet Med 20:301-6 |
Showing the most recent 10 out of 66 publications
