Project 451563

Diamond-Blackfan anemia (DBA) is a rare congenital disease that is usually diagnosed before 2 years of age. Clinical presentation includes severe anemia, growth retardation and failure to thrive. Patients display various levels of disease severity for reasons that are not completely understood. Current treatments include repeated blood transfusions, life-long steroids administration, and hematopoietic stem cell transplantation. Unfortunately, these treatments are often associated to severe side effects that can affect children development and patients' quality of life. Thus, novel, less toxic therapeutic approaches are critically needed. While we know that DBA is due to a failure of the bone marrow to produce functional red blood cells, the mechanism of disease development remains unclear. Recent results have shown that DBA is caused by a general defect in blood stem cells to produce the correct amounts of proteins, ultimately leading to a failure in the formation and function of red blood cells. However, it is currently unclear what are the specific proteins that are affected in the disease and we do not understand how such a decrease in protein levels causes the disease. In this application, we propose to use novel techniques we have previously established to identify all proteins that are defective in DBA, and to determine how these defects cause defects in red blood cells. The proposed project is expected to pave the way to new therapeutic approaches in the future.