Diamond Blackfan Anemia (DBA) is a disease that results in anemia, birth defects, and increased risk of cancer. The treatment for patients with DBA results in significant complications and late effects. Approximately 25% of DBA patients have mutations in a ribosome protein known as RPS19. To understand the reasons why DBA patients develop anemia, we made a zebrafish model with low RPS19 levels. This resulted in anemia and birth defects similar to DBA patients. We are proposing experiments to understand genes that are abnormally turned on or off in cells with low levels of RPS19. We found that a small RNA, microRNA34a (miR34a) is more abundant in blood stem cells with low levels of RPS19. We propose experiments to study the how miR34a might lead to abnormalities in blood cell production in cultured cells and mouse models. We will also use a new technology known as RNA-seq to find new genes that are abnormally regulated in blood stem cells that express lower levels of RPS19. Our studies will lead to new information to better understand DBA and previously undiscovered approaches to treat this disease.