Molecule analysis of blood cell development has served as an important paradigm for stem cell biology. We have obtained a solid foundation in understanding how commitment to specific lineages is programmed and cell-specific patterns of gene expression are established. We are interested in how hematopoietic, and other, stem cells transcriptionally control developmental potency and how aberration may precipitate oncogenesis.

Our studies have focused primarily on the in vivo roles of transcriptional regulators in cell specification and differentiation. Studies involved diverse approaches, including conventional and conditional gene targeting, and proteomics. We have characterized the roles of several major transcription factors in blood cell development, and how abnormalities in these lead to malignancy. Ongoing projects include the following: 1. Epigenetic regulation of hematopoietic stem cells, individual blood lineages, and ES cells; 2. Dissecting the genetics of one form of early childhood leukemia using hES and iPS cells; 3. Defining the control of fetal hemoglobin (HbF) in humans and reactivation of HbF in adults; 4. Chemical and biological approaches to HbF reactivation; 5. Use of gene editing to modify hematopoietic stem cells; and 6. Mechanisms of hematopoietic cell reprogramming.