My research has primarily concerned the investigation of the molecular pathogenesis of the myelodysplastic syndromes (MDS), a heterogeneous group of myeloid malignancies. We have performed the largest study to date of gene expression profiling in MDS and this work has resulted in the identification of key genes and pathways deregulated in this disorder. We have also identified a gene expression profiling-based signature for assessing prognosis in MDS. More recently we have explored the interconnections among mutations, gene expression, clinical variables and patient outcome in MDS. Our study of the MDS transcriptome using RNA sequencing has identified key downstream target genes that are aberrantly spliced in association with spliceosome gene mutations in MDS. Mutation of the splicing factor SF3B1 is strongly associated with the MDS subtype RARS and we have implicated aberrant splicing of the downstream target gene ABCB7 in the pathophysiology of RARS. We have also identified the key target genes of the mutant splicing factor gene U2AF1 in the cell lineages affected in MDS. These data have critical implications for understanding MDS phenotypic heterogeneity and support the development of therapies targeting splicing abnormalities.