The goal of our research is to understand how adult stem cells maintain tissue function, how their differentiation is regulated, how these processes are altered or disturbed during aging and in cancer.
We study the hematopoietic system to understand how transcription factors regulate lineage specification, and to identify the cellular pathways of lineage commitment. We are particularly interested in how the non-lymphoid cell types (erythrocytes, megakaryocytes, granulocytes and macrophages) are generated, and in particular in how antagonism between the transcription factors that specific myeloid cells (PU.1, C/EBP) and megakaryocytic/erythroid cells (GATA-1, FOG-1) leads to irreversible lineage commitment.
We also study hematopoietic stem cells (HSCs), with particular emphasis on their expression of genes characteristic of multiple mature cell types, so called lineage priming. We are using fluorescent reporters to isolate HSCs with particular lineage priming patterns, and to study how the HSC population changes when the organisms ages.
Finally, we generate accurate genetic models of human acute myeloid leukemia, and study their impact on HSCs and progenitors, as well as the mechanisms by which they lead to the formation of malignant leukemic stem cells.