Silvia FRE
Notch signaling in stem cells and tumors
Notch signaling in stem cells and tumors
KEYWORDS: Intestinal stem cells, mammary gland, prostate
Mouse models, 3D organoids
Notch signaling, Wnt signaling, Lineage tracing
Regeneration, cell proliferation, cell fate determination, tumor heterogeneity
Mouse models, 3D organoids
Notch signaling, Wnt signaling, Lineage tracing
Regeneration, cell proliferation, cell fate determination, tumor heterogeneity
Our research is focused on the in vivo study of normal and malignant stem cells during development and tissue homeostasis in vivo in three dynamic epithelial tissues, the intestine, the mammary gland and the prostate. These tissues are particularly suited for our studies, because they are harbor highly active stem cells, to ensure extremely rapid and continuous cell renewal in the case of the intestinal epithelium and to guarantee remarkable tissue remodeling upon hormonal stimulation in the case of the mammary gland and the prostate following castration.
Our main experimental approach is based on lineage-tracing studies, to genetically label stem cells and follow their lineages and behavior in vivo during development, tissue remodeling and regeneration and in tumors. Through innovative experiments in 3D organotypic cultures as well as in mice, we aim at defining the distinguishing features of stem cells. Based on the extensive evidence linking the Notch pathway to stem and progenitor cells in a variety of tissues, we have chosen to mark these cells by the expression of the four Notch receptors. For this purpose, we have recently developed a novel set of unique transgenic mice that allow us to assess and dynamically follow Notch expression and activation in vivo.
We also dissect the involvement of Notch in stem cell homeostasis and in cancer initiation. To achieve this goal, we combine the analysis of Notch-specific cell lineages with functional studies to determine and manipulate the fate of cells associated with Notch activity in both normal and cancer tissues. These studies will provide insights into the regulatory mechanisms controlling the maintenance, repair and regeneration of tissues, the basis for the development of effective therapeutic applications of stem cells in regenerative medicine.
Our ultimate goal is to explore the signals controlling stem cell homeostasis, in order to gain mechanistic insights into organ morphogenesis, but also into the cellular hierarchy of the highly heterogeneous tumor cell populations.
Our main experimental approach is based on lineage-tracing studies, to genetically label stem cells and follow their lineages and behavior in vivo during development, tissue remodeling and regeneration and in tumors. Through innovative experiments in 3D organotypic cultures as well as in mice, we aim at defining the distinguishing features of stem cells. Based on the extensive evidence linking the Notch pathway to stem and progenitor cells in a variety of tissues, we have chosen to mark these cells by the expression of the four Notch receptors. For this purpose, we have recently developed a novel set of unique transgenic mice that allow us to assess and dynamically follow Notch expression and activation in vivo.
We also dissect the involvement of Notch in stem cell homeostasis and in cancer initiation. To achieve this goal, we combine the analysis of Notch-specific cell lineages with functional studies to determine and manipulate the fate of cells associated with Notch activity in both normal and cancer tissues. These studies will provide insights into the regulatory mechanisms controlling the maintenance, repair and regeneration of tissues, the basis for the development of effective therapeutic applications of stem cells in regenerative medicine.
Our ultimate goal is to explore the signals controlling stem cell homeostasis, in order to gain mechanistic insights into organ morphogenesis, but also into the cellular hierarchy of the highly heterogeneous tumor cell populations.
