Molecular Mechanisms and Targeting of Pre-Cancerous and Cancer Stem Cells in Normal and Malignant Hematopoiesis
Glycotyping stem and progenitor cells
Hematopoiesis maintains a life-long supply of the entire spectrum of highly specialized blood cells dependent on systemic needs. This process relies on a tightly regulated balance of self-renewal, commitment, and differentiation of a small number of pluripotent hematopoietic stem cells (HSC).
Recent experimental evidence has shown that acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) arise from an unexepctedly diverse pool of pre-leukemic stem cells (pre-LSC), preceding the formation of fully transformed leukemia stem cells (LSC). Pre-LSC as well as LSC are characterized by a relative resistance to chemotherapy and thereby contribute to treatment failure. Defining the molecular characteristics and mechanisms in pre-LSC and their progression to fully transformed LSC is critical to understanding the genesis of leukemia and to developing therapeutic strategies by which these processes can be targeted.
The goal of our research is to delineate critical mechanisms in HSC that drive formation and function of pre-LSC and LSC. We are studying murine genetic models as well as primary human samples from patients with MDS and leukemia. Our studies aim at the development of targeted, pre-LSC- and LSC-directed therapies, which could ultimately also be employed for precision prevention of relapse/progression, or "cancer interception".