Project A – Stiffness of leukemic stem cells
Investigation of the following hypotheses:
- Hematopoietic stem cells (HSCs) differ from committed progenitor cells and mature cells in terms of stiffness, dependent on niche interactions and their glycolytic state;
- Leukemic stem cells (LSCs) differ from normal hematopoietic stem cells in terms of stiffness, dependent on genetic alterations, niche interactions and their glycolytic state;
- Interfering with stem cell-niche interactions will impact on cellular stiffness and their metabolic state, thereby providing alternative means for targeting.
Research in this project involves:
- Using colloidal-tip indentation with AFM to measure differences between the stiffness of HSCs, progenitor cells and LSCs; this will be done on cells from primary leukemia patients as well as lentiviral leukemia models where known oncogenes can be introduced.
- Simultaneous determination of levels and localization of YAP using GFP reporters linked to integrin and/or GPCR activation.
- Simultaneous visualization of stress fibers and mapping of local stiffness distribution inside individual cells when adhered to patterned surfaces.
- Functionally evaluate whether interfering with LSC-niche interactions or by inferring with the glycolytic state of LSCs impacts cellular stiffness and drug sensitivity.