Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Sickle cell disease (SCD) is a genetic disorder that affects millions of individuals worldwide. This disease is especially prevalent in developing countries. Although no official statistics are available, it is estimated that 15-20,000 Canadians suffer from this disease. In the United-States, the healthcare costs associated to a single SCD patient with a life expectancy of 50 years old elevates to more than $8 million. In developing nations, where appropriate care for this disease is less accessible, half of the children born with SCD will die before their fifth birthday. Current treatments are either inaccessible or ineffective. A promising approach for the treatment of this disease is the reactivation of fetal hemoglobin (HbF) production. The aim of this project is to identify genes that would be attractive targets for pharmaceutical induction of HbF. The first part of this project consists in the generation of comprehensive functional (DNA methylation and transcriptomic) datasets on the regulation of HbF in human cells. We will combine these genomic results with results from genetic association analyses performed in large cohorts of SCD patients. These two approaches (genomic and genetic) will provide complementary information to identify new genes that regulate HbF production in humans. Our project will generate important functional datasets, which will not only be relevant for SCD but also for multiple hematological processes and disorders. Thus, we will make these datasets publicly available to the scientific community. The genetic association studies will highlight genes that represent attractive targets for the treatment of SCD, as well as biomarkers of its complications. The development of a specific therapy for SCD is crucial, as the number of affected individuals continues to grow.