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Claudia Waskow - Regeneration in Hematopoiesis

Research

Stem cells are the natural unit of embryonic generation and adult regeneration. The constant supply of de novo generated mature cells from adult stem cells is pivotal for the lifelong function of many organs, in particular for tissues with high turn-over rates such as gut, skin and blood. The major features of continued tissue formation include balancing self-renewal and differentiation of stem cells over extended periods of time while preventing carcinogenic transformation by orchestrating factors regulating fate choice decisions.

One of the most thoroughly studied adult stem cells are hematopoietic stem cells (HSC) that give rise to all types of mature blood cells throughout life, a process called hematopoiesis. HSC are the only adult stem cell type that is routinely used in the clinic for the replacement of diseased blood tissues. In fact, bone marrow transplantation from healthy individuals into patients still remains the only cure, not only for primary immune deficiencies, but also for acquired states of bone marrow failure including certain leukemia and anemia. HSC can be prospectively isoltated to very high purity, however, despite the precise phenotypic description of HSC and more differentiated progenitors, mechansism regulating their cell fate decisions are not resolved. Fate possibilities comprise self-renewal, differentiation, programmed cell death and emigration, and they are clearly regulated by cell intrinsic and extrinsic mechanisms.

We aim at understanding the regulation of HSC function to modulate and improve therapeutic approaches in the future. Fundamental unresolved questions that we work on include: How is hematopoiesis controlled on the cellular and molecular level? What keeps a stem cell a stem cell? What invites a stem cell to differentiate? What is the role of growth factors in lineage choice?

To answer these questions we focus our research on:

  • Analysis of HSC function - clonal level, extrinsic and intrinsic regulation
  • Improving mouse recipients for the study of human and mouse HSCs
  • Analysis of human leukemic stem cells - characterization and regulation