Sickle cell disease (SCD) is a genetic disorder of hemoglobin and afflicts ~110,000 African-Americans in the US. Because of its complex pathophysiology through chronic hemolytic anemia, microvascularocclusion, and a chronic inflammatory state, it affects multiple organ systems and leads to significant morbidity and organ damage as well as leads to frequent hospitalizations and health care encounters. During the past 35 years, primarily through research and patient care conducted by the NIH funded Comprehensive Sickle Cell Centers and some pivotal clinical trials, the life expectancy of patients with SCD has increased from the teens to mid- to late forties. This is still considerably shorter than that of African-Americans who do not have sickle cell disease and can be viewed as a major disparity even in this underserved minority population. While significant advances have been made in the understanding of the disease pathophysiology and in novel therapies through basic and translational research, these advances have been slow to be taken to clinical practice. The Southeastern Exploratory Sickle Cell Center of Excellence seeks to improve the care and quality of life of the SCD patient population by i) investigating the basic mechanism of action of a highly successful and effective hemoglobin F inducing drug, hydroxyurea, ii) identifying genetic variations underlying the frequency of pain, response to narcotics, and thus addressing the important issue of biologic/genetic bases of pain and its under treatment leading to the stigmatization of many SCD patients and its resulting disparity, iii) investigating the medical, social, and economic reasons for underutilization of hydroxyurea in SCD, iv) training primary care physicians with evidence based medicine in the care of patients with SCD, given the sobering reality that there will not be enough specialists in non-malignant hematology to meet the needs of the growing adult SCD population, and v) implementing innovative methods and concepts for the care of SCD patients in the ED and for transitioning from pediatric to adult care. Relieving the health disparity of SCD patients is the primary goal of this application.

Public Health Relevance

Sickle cell disease in the United States primarily affects African-Americans and is considered an orphan disease. Because of the lack of knowledge of health care providers in the management and treatment of painful episodes and other complications of this disease, patients are most often undertreated or not treated at all, which has created an enormous health disparity for these patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD003383-04
Application #
8211068
Study Section
Special Emphasis Panel (ZRG1-EMNR-L (52))
Program Officer
Tabor, Derrick C
Project Start
2009-05-28
Project End
2013-12-31
Budget Start
2012-01-05
Budget End
2012-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$1,371,402
Indirect Cost
$476,540
Name
Georgia Regents University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912
Ikuta, Tohru; Sellak, Hassan; Odo, Nadine et al. (2016) Nitric Oxide-cGMP Signaling Stimulates Erythropoiesis through Multiple Lineage-Specific Transcription Factors: Clinical Implications and a Novel Target for Erythropoiesis. PLoS One 11:e0144561
Piel, Frédéric B; Adamkiewicz, Thomas V; Amendah, Djesika et al. (2016) Observed and expected frequencies of structural hemoglobin variants in newborn screening surveys in Africa and the Middle East: deviations from Hardy-Weinberg equilibrium. Genet Med 18:265-74
Anea, Ciprian B; Lyon, Matthew; Lee, Itia A et al. (2016) Pulmonary platelet thrombi and vascular pathology in acute chest syndrome in patients with sickle cell disease. Am J Hematol 91:173-8
Jaja, Cheedy; Bowman, Latanya; Wells, Leigh et al. (2015) Preemptive Genotyping of CYP2C8 and CYP2C9 Allelic Variants Involved in NSAIDs Metabolism for Sickle Cell Disease Pain Management. Clin Transl Sci 8:272-80
Baker, Charlotte; Grant, Althea M; George, Mary G et al. (2015) Contribution of Sickle Cell Disease to the Pediatric Stroke Burden Among Hospital Discharges of African-Americans-United States, 1997-2012. Pediatr Blood Cancer 62:2076-81
Jaja, Cheedy; Patel, Niren; Scott, Stuart A et al. (2014) CYP2C9 allelic variants and frequencies in a pediatric sickle cell disease cohort: implications for NSAIDs pharmacotherapy. Clin Transl Sci 7:396-401
Gutsaeva, Diana R; Montero-Huerta, Pedro; Parkerson, James B et al. (2014) Molecular mechanisms underlying synergistic adhesion of sickle red blood cells by hypoxia and low nitric oxide bioavailability. Blood 123:1917-26
Ghoshal, Pushpankur; Rajendran, Mythilypriya; Odo, Nadine et al. (2014) Glycosylation inhibitors efficiently inhibit P-selectin-mediated cell adhesion to endothelial cells. PLoS One 9:e99363
Ikuta, Tohru; Kuroyanagi, Yuichi; Odo, Nadine et al. (2013) A common signaling pathway is activated in erythroid cells expressing high levels of fetal hemoglobin: a potential role for cAMP-elevating agents in β-globin disorders. J Blood Med 4:149-59
Zhu, Xingguo; Wang, Yongchao; Pi, Wenhu et al. (2012) NF-Y recruits both transcription activator and repressor to modulate tissue- and developmental stage-specific expression of human γ-globin gene. PLoS One 7:e47175

Showing the most recent 10 out of 17 publications