PROJECT SUMMARY

Myelodysplastic syndromes (MDS) are a heterogenous group of blood disorders in which the bone marrow does not produce blood effectively. MDS typically has poor prognosis, in part because there are few treatment options, and most of the available therapies are not curative. The paucity of available therapies is largely due to our incomplete understanding of the biological and molecular mechanisms underlying the disease.

In this proposal, we will combine experimental and computational tools to determine how a common genetic change gives rise to MDS. Mutations affecting the gene ZRSR2, which encodes a protein involved in a molecular process called RNA splicing, are common in MDS. Although ZRSR2 mutations occur frequently, it is not known why they prevent normal blood production and give rise to MDS. We will determine how ZRSR2 mutations drive the development of MDS and search for new ways to specifically target and kill cells carrying ZRSR2 mutations. The long-term goals of this research are to further our understanding of basic MDS biology and identify potential new therapies for this disease.