The formation of blood cellular components or hematopoiesis is a complex process regulated by genetic and epigenetic mechanisms. To ensure continuous blood cell production is necessary to preserve hematopoietic stem cells (HSC) in a resting state while preserving their capacity to differentiate on demand into different blood lineages via hematopoietic progenitor cells (HPC). The primary focus of the Lacorazza lab is to study the molecular control of normal production of blood cells and malignant hematopoiesis. Our studies concentrate on two critical properties of HSCs: quiescence (reversible cell cycle arrest) and self-renewal (a specialized cell division producing daughter cells identical to the parental cell).
The mechanisms of HSC maintenance are hijacked during the leukemogenic transformation of hematopoietic stem/progenitor cells into a rare population known as leukemic stem cells (LSC) or leukemia-initiating cells (LIC) that feed leukemia. The current paradigm is that the LSC population drives refractory and relapsed disease. Therefore, many groups are focused on identifying targets for developing LSC-specific therapies to eradicate this chemoresistant leukemic reservoir. We combine genetic mouse models and pre-clinical mouse models using patient samples to study genes involved in pediatric (acute lymphoblastic leukemia) and adult (chronic myeloid leukemia and acute myeloid leukemia) leukemias.