Our research team studies the mechanisms that determine the generation and diversification of blood cells from a very small number of multipotent hematopoietic stem cells. Their multipotentiality is maintained by a complex network of transcription factors. We have observed that an intrinsic disruption of this network by oncogenes perturbs basic cellular functions and induces leukemia.
How differentiation emerges and how cells integrate signals from the environment to keep the hematopoietic system stable are questions of interest. Current investigation involves cellular studies of transgenic or knock-out mouse models, combined with functional proteomic and genomic approaches, as well as targeted molecular studies.
One of the team's discoveries has revealed that a gene called Stem Cell Leukemia (SCL) plays a critical role in blood cell formation, by nucleating a large transcriptional complex on DNA with its partner LMO2. Chromosomal translocations cause ectopic SCL or LMO2 expression in the thymus, resulting in leukemia.