Our studies have focused on analyzing the regulation of neutrophil-specific gene expression and function and its disruption in myelodysplasia and acute leukemia. We have focused on the positive regulation of normal neutrophil maturation by the C/EBP family of transcription factors, particularly C/EBPalpha and C/EBPepsilon, and the negative regulatory role played by CDP/cut, in mediating late myeloid gene expression. We have also characterized the role of Gfi-1 and C/EBPepsilon in the etiology of the rare inherited neutrophil disorder, specific granule deficiency (SGD). In more recent studies, we have collaborated with Dr Pandolfi (BIDMC) to characterize the role of the nucleolar phosphoprotein NPM1, the most commonly mutated gene in normal karyotype (NK) AMLs, as a coactivator of C/EBPalpha mediated transcription during neutrophil maturation. This finding may explain the defective myeloid phenotype observed when NPM1 expression is compromised in MDS and AML. Further analysis of the role played by C/EBPalpha and NPM1 in NK-AML are underway.