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Mechanisms of quality control that act to maximize tissue health, or “fitness,” on the cellular and tissue level have not been well defined. Our research group studies quality control during tissue morphogenesis and maintenance through the lens of cell competition. Cell competition is a conserved, yet poorly understood, phenomenon of growth control that is likely to have serious implications for heterogeneous cell-cell interactions within tissues and in stem cells during development, homeostasis, and in disease. Research in our group explores the molecular and cellular mechanisms that underlie competitive behaviours. Our studies test the hypothesis that cell competition plays a central, protective role in shaping the tissue-level response to stresses.
Our group employs a multidisciplinary tool-kit – drawing from genetics, cell biology and quantitative biology - to ask mechanistic questions about epithelial tissue organisation and growth control across scales. We use the mouse skin as a model system because it has a well-defined developmental program, is genetically tractable, and is compatible with our favourite approaches to study cell behaviour and cell-cell interactions – immunofluorescence and live imaging! We previously established the skin as a physiologically relevant system in which to study mammalian cell competition. Our ultimate goal is to use our tools to uncover basic principles of growth control in complex epithelial tissues as they grow, differentiate, reach their final size, and contend with threats to their homeostasis.
Stephanie obtained her PhD from the University of British Columbia where she studied cell adhesion in the fly embryo with Guy Tanentzapf. She then completed her post-doctoral training with Elaine Fuchs at Rockefeller University supported by HFSP, NYSCF and NIH-K99 fellowships. Stephanie opened her research group at the Max Perutz Labs as an Assistant Professor at the University of Vienna in February 2022.
We previously found that cell competition is essential for barrier formation in skin. However, what determines fitness on a molecular level, and indeed, whether fitness is a heritable trait, remains unexplored. We use transcriptomics, functional genetics, lineage tracing and live imaging to uncover novel genes and cell behaviours that confer fitness in skin progenitors during growth/regeneration.
We previously identified a developmentally-regulated switch in the mode by which less fit cells are eliminated from the epidermis. The signals that mediate this transition and ensure maintenance of epithelial integrity during elimination events are unknown. We have identified candidate regulators of this process that we will interrogate via functional genetics and quantitative imaging approaches.
Cell competition is proposed to impinge on tumour initiation/progression as a tumour suppressor in some contexts and as a malignant driver in others. Our group will use models of squamous cell carcinoma to clarify the role of cell competition in tumorigenesis, and moreover, to understand the perceived threshold that determines whether cell competition will restrain or promote oncogenic growth.
Many inflammatory genetic diseases manifest mosaically in patients. We hypothesize that cell competition underlies the etiology of these diseases and will use mouse and organoid models to interrogate this possibility. In the long term, our strategy may inform new therapeutic avenues.
Stem cell progeny liaisons in regeneration.
Ellis, Stephanie J; Fuchs, Elaine
Distinct modes of cell competition shape mammalian tissue morphogenesis.
Ellis, Stephanie J; Gomez, Nicholas C; Levorse, John; Mertz, Aaron F; Ge, Yejing; Fuchs, Elaine
Basal Cell-Extracellular Matrix Adhesion Regulates Force Transmission during Tissue Morphogenesis.
Goodwin, Katharine; Ellis, Stephanie J; Lostchuck, Emily; Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo; Tanentzapf, Guy