Grant: Project Grant

Sickle cell disease (SCD) is a genetic disease of the blood that affects nearly 10 million individuals worldwide. In Canada, more than 5000 citizens, mostly of African descent, suffer from SCD. The disease is caused by a mutation that affect the beta-globin gene, which codes for a protein that forms hemoglobin. Patients with SCD are anemic, but can also suffer from severe complications that affect the hematological (e.g. leukemia), but also the neurological (e.g. stroke) and cardiovascular (e.g. heart failure) systems. There are no good lab tests that doctors can use to predict which patients will develop which complications. And the therapeutic options to treat SCD patients are limited and have variable success. The goal of our CIHR Project grant application is to develop new tools to help prevent and treat SCD-related complications. We use human genetics and other methodologies to understand why some patients have a severe form of the disease whereas others are largely unaffected. In particular, we will measure proteins in the plasma of patients with severe and mild disease to find "biomarkers" that could help identify patients that would benefit from more intensive clinical follow-up. We will also explore if these so-called "biomarkers" could be tested as potential drug targets. We will also characterize the cells that form blood to understand if their "gene expression programs" are abnormal in patients with SCD. And finally, we will combine all our knowledge and attempt to develop genetic tests that could be used to prioritize SCD patients more likely to suffer from severe complications.