PROJECT SUMMARY

The goal of my research program is to determine the causes and consequences of DNA mutations in blood cells that impact myelodysplastic syndromes (MDS), leveraging insights from populations with high-risk to blood-based diseases. In blood-based diseases, the distribution of cells is abnormal, the key feature of MDS. Despite the insight we could derive from people predisposed to blood-based diseases, there is little understanding of the mutations of the blood in these people. Notably, people with Down syndrome (DS) have disruptions in their blood systems, making them critical for MDS studies. Therefore, we will study blood mutations in people with DS to understand MDS pathology and pursue potential treatments.

We previously characterized mutations in people with DS and observed an abundance of mutations in a gene called TET2. TET2 is a gene that is commonly mutated early in disease, making it ideal to investigate MDS. For the first project, we will determine if the DS context promotes TET2 mutations and the results of this promotion. Furthermore, inflammation is known to cause the onset of and exacerbate MDS. However, changes in inflammation are understudied in MDS. Using mouse models of DS with varying levels of inflammation, we will investigate how inflammation and blood mutations impact each other in MDS for the second project. In both projects, we will learn how MDS develops and establish treatment options to enhance the quality of life for MDS patients.