Research SummarySenior Fellowship research summary
Stem cells are a unique class of cells from which all other cell types in our body originate. Properties that set them apart from other cells are the ability to (i) produce more cells of their own kind through self-renewal and (ii) generate cells of different identities and specialized functions. Because of these properties, stem cells can replenish cellular losses in the body due to depletion and damage, yet maintain their own reserve. This makes stem cells useful for regenerative medicine and cell-based therapies. Understanding the mechanisms of self-renewal is, therefore, important in basic science and biomedicine.
Stem cells of epithelial origin survive the stress of anchorage-deprivation and self-renew to form spheres in suspension culture, while most normal epithelial cells die when deprived of anchorage. Growth in three-dimension additionally imposes the stresses of hypoxia and nutrient deprivation. While little is known about how stem cells counter such stresses, mechanisms utilized by cancer cells to evade the stresses of three-dimensional growth has been well-studied. Recent research, including studies from my laboratory, has highlighted the importance of AMP-activated protein kinase (AMPK) in cancer cells under stresses of hypoxia, nutrient deprivation, and anchorage-independence. Since stem cells share fundamental properties with cancer cells, we plan to test the hypothesis that the AMPK-defined molecular pathways that enable cancer cells to survive the stresses of three-dimensional growth also play critical roles in sphere-formation by stem cells in non-adherent, suspension condition.
Mammospheres stained for Epithelial Surface Antigen (ESA; green) and Propidium iodide (PI; Red)Figure Legend: Mammospheres stained for Epithelial Surface Antigen (ESA; green) and Propidium iodide (PI; Red)