Project A – Stiffness of leukemic stem cells

Objectives

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.

Description

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.