Variation in Severity of Sickle Cell Disease among the Yorubas
PI: R. Cooper
NIH/Fogarty International Center 07/01/2011 – 06/30/2014
In this project we propose to build on two decades of collaborative research in the West African diaspora to link investigators in Nigeria and Jamaica with institutions in North America to build research capacity in SCD and advance our understanding of the genetic influences on severity. We further propose to enhance the clinical SCD activities at the collaborating institution in Nigeria, provide training for our Nigerian collaborator, and create a model for outcomes and management research in the region. Read more...
Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment with Hydroxyurea
PI: B Tayo, V. Gordeuk
Doris Duke Charitable Foundation 9/1/2013-8/30/2016
The purpose of this study is to provide comprehensive evidence on short-term (i.e., primarily hematologic) outcomes and safety in order to provide the necessary empirical data base to encourage widespread adoption of a low fixed-dose regimen of HU in Africa. Further, we propose to train local clinical “champions” to be change-agents who can spread the message on the value of HU through university hospitals, sickle cell organizations and government agencies in West Africa.
Endothelial Barrier Phenotypes in Sickle Cell Disease
PI: S. Ofori-Acquah
NIH/NHLBI 07/01/2011 – 06/30/2016
The goal of this R01 project is determine whether sickle cell disease accelerates age-dependent increase in oxidative stress sufficiently to contribute to premature development of vascular barrier dysfunction in relatively young mice. We will test the hypothesis Nrf2 expressed in the vascular wall dominantly regulates the cytoprotective response to hemolytic and oxidative stress in SCD, to the extent that loss of this function will result in several vascular inflammation, and pulmonary vascular dysfunction. Furthermore, we will test the hypothesis that prophylaxis using Nrf2-activating nutraceuticals in young SCD mice would slow-down progression of pulmonary vascular dysfunction. This study has direct translational appeal, since such nutraceuticals can readily be tested in SCD patients, if we get favourable results in mice.
Cellular Mechanisms of Acute Lung Injury in Sickle Cell Disease
PI: S. Ofori-Acquah, C. Joiner, MR. DeBaun
This is a U01 Center of Excellence in Hemoglobinopathy Research Award with Dr. Ofori-Acquah as the Scientific Director. The goal of this project is define the role of endothelial adhesion molecules and intermediates of TLR4 in an experimental model of acute chest syndrome developed by the Ofori-Acquah group(3) . A second major focus of this award is to screen several drugs, which have already been used in humans for other conditions, targeting the HO-1 and TLR4 pathways, for repurposing in SCD. Finally, we will sequence ~30 genes in the HO-1 and TLR4 pathways in a large cohort of SCD patients of predominantly African American origin, to look for additional polymorphisms associated with ACS risk. This project offers a unique opportunity for several ancillary studies in Africa, focused broadly on hemin catabolism and inflammation/anti-inflammation.
Translating genetic discoveries to improve sickle cell disease prognosis and treatment
PI: Lettre and Hirschhorn
Doris Duke Charitable Foundation 2012/11-2015/10
Using complementary genetic strategies, our group has identified novel genes and biological pathways involved in modulating clinical severity in SCD. The goal of this grant is to explore novel strategies to implement these genetic discoveries in order to derive new clinical biomarkers and treatment interventions for SCD.
Exploring Perspectives on Genomics and Sickle Cell Public Health Interventions
PI: Ambroise Wonkam
NIH/H3Africa 09/20/2013 – 07/31/2014
A major objective of this pilot project is to advance our understanding of the perspectives of researchers, health professionals, and community populations within our collaborative network concerning both genomic research and the public health aspects of SCD. We will employ qualitative research methods to pursue the following specific aims:
Aim 1: Explore perspectives and attitudes regarding genomic research and its implementation and implications in Cameroon, Ghana and Tanzania.
Aim 2: Assess perceptions about public health interventions to increase awareness, early detection, and prevention of SCD-related complications.
This research is the first phase of a series of longitudinal, mixed method studies exploring individual, family, community, and professional perspectives on genomic research and SCD-related public health interventions. This formative research will help us to define the most effective strategies for: 1) implementing genomic research and addressing the pertinent issues and 2) insuring informed decision-making about and optimal uptake of newborn screening, other public health interventions for SCD, and the related services.