Our research program is focused on dissecting the molecular regulation of normal and malignant HSC self-renewal and hopes to identify the underlying processes that ultimately lead to leukemic transformation and progression. In lower organisms such as the fruit fly, cell polarization coupled with the asymmetric inheritance of fate determinants is critical in for regenerating stem cell pools while simultaneously ensuring production of all required differentiated cell types. When dysregulated however, these processes contribute instead towards malignant progression and the formation of tumors driven by stem cells that divide unchecked. Because of their importance in other stem cell systems, our research will pay particular attention to defining the role that polarity and asymmetric cell division proteins may play in the maintenance and/or expansion of mouse and human HSC and leukemic stem cells (LSC). With this work we aim to provide advances that will have implications for the development of novel methods to amplify HSC for use in regenerative therapies or to reign in constitutively self-renewing leukemia cells.