Ellen J. Ezratty, PhD
- Assistant Professor of Pathology & Cell Biology in Dermatology
Credentials & Experience
Education & Training
- BS, Pennsylvania State University
- PhD, Columbia University
One fundamental question in developmental and stem cell biology is how an individual cell may sense its environment to transmit extracellular signals that control cell signaling and proliferation during tissue morphogenesis, homeostasis and regeneration. The activation of cell signaling pathways must be temporally and spatially regulated in order to balance tissue growth with differentiation. When this goes awry during normal tissue homeostasis, proliferative conditions such as polycystic kidney disease (PKD) and cancer arise. The long-term objective of my research is to understand how primary cilia temporally and spatially regulate cell signaling and proliferation in tissue stem cells.
Almost every vertebrate cell - including both embryonic and tissue stem cells - display a single, hair-like projection called a primary cilium. Once thought merely a vestigial structure, it is now well established that cilia are cell-sensory organelles that coordinate a wide variety of signal transduction pathways, including Wnt, Hedgehog, Notch, PDGFα and integrin signaling. This appreciation of cilia as cellular “antennae” that sense a wide variety of signals likely explains why ciliary defects contribute to diverse human disorders and diseases, such as polydactyly, neural tube defects, Bardet-Biedl Syndrome, retinal degeneration, Polycystic Kidney Disease (PKD), and skin cancer. It is therefore relevant to study ciliary function in tissue stem cells, since dysfunctional cilia are associated with diseases that precipitate the transition from cellular quiescence to proliferation, such as PKD and cancer.
I’ve established the skin as a model system to probe ciliary function in tissue stem cells. The epidermis is a highly regenerative tissue that contains at least two different populations of stem cells that are ciliated throughout embryonic development, homeostasis and tissue regeneration. Skin epidermis and its appendages, notably hair follicles, provide an essential barrier that is constantly renewed during the lifetime of an organism. Homeostatic renewal of both epithelial tissues, as well as repair of damage, requires activation of stem cells. Stem cells reside in the innermost basal layer of epidermis and in a specialized compartment of the hair follicle referred to as the bulge. A microenvironment or “niche” maintains bulge stem cells in a quiescent and undifferentiated state. However, pulse-chase labeling, lineage analysis, and transplantation studies show that when these cells are needed either for hair follicle regeneration during the hair cycle or for replenishing damaged epidermis after injury, bulge stem cells become activated.
Stem cells must sense their microenvironment or “niche” to transmit extracellular signals that either maintain tissue homeostasis or promote regeneration after injury. The primary cilium has emerged as a candidate for such sensory function: this microtubule-based cellular “antennae” can sense the extracellular environment, co-ordinate signal transduction pathways, and influence cell-cycle progression. Primary cilia play at least two temporally and spatially distinct roles in balancing growth and differentiation during skin development: a novel, early role in epidermis, whose morphogenesis relies upon Notch signaling; and a later role in hair follicles, reliant upon Sonic Hedgehog signaling. Although the reliance of Shh signaling on cilia is expected and well characterized in other model systems, the molecular mechanisms underlying cilia-mediated control of Notch signaling and regulation of cell proliferation during epidermal morphogenesis are unknown. Current projects in the laboratory focus on dissecting the molecular mechanisms that dictate how primary cilia temporally and spatially regulate cell signaling and cell proliferation during epidermal and hair follicle development, tissue homeostasis and regeneration.
- Function of primary cilia in tissue stem cells
COLUMBIA UNIVERSITY SKIN DISEASE RESOURCE-BASED CENTER (EPICURE) (Federal Gov)
Aug 1 2016 - Jul 31 2021
FUNCTION OF PRIMARY CILIA DURING EPIDERMAL MORPHOGENESIS (Federal Gov)
Sep 1 2014 - Aug 31 2017
MECHANISMS OF INTEGRIN-MICROTUBULE CROSS-TALK (Federal Gov)
Aug 1 2003 - Jul 31 2011