Grant: CIHR Fellowship

Over 300,000 children are born each year with sickle cell disease (SCD) or b-thalassemia, which are the most common genetic disorders worldwide. These diseases are caused by genetic changes in hemoglobin, which is important for the oxygen carrying ability of red blood cells (RBCs). As such, this causes RBCs to have impaired functioning, shape, and development. These patients face frequent health issues and often develop severe pain, organ damage, and infections. However, there are currently no effective treatments. Interestingly, patients who have more of the fetal form of hemoglobin (HbF) relative to the adult form do better clinically. As such, finding effective ways to increase fetal hemoglobin is a promising strategy to drastically improve patient treatment and quality of life. Recently, our lab studied DNA from over 25,000 people and found genetic changes near a gene called BACH2 that are associated with changes in HbF levels. Using cutting edge genetics technologies, we deleted this DNA region and found that it led to a reduction in BACH2. We believe that this region influences BACH2 expression and thus HbF levels and could be a potential treatment target for treating SCD. In the proposed research, we will work to carefully understand how the DNA region and BACH2 could change HbF levels. As this is the first time BACH2 has ever been associated with variation in HbF levels, this study will not only significantly expand our understanding of this gene in HbF regulation, but will greatly benefit patients with SCD or b-thalassemia by informing the development and implementation of new and potentially more effective treatment strategies.