Group Stephanie Ellis

Cell Competition and Tissue Fitness in Development and Disease

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The Question

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.

The Approach

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 Ellis

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.

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Spotlights

PhD Call 2024

 

Stephanie Ellis gives a short overview of her research, her lab and what future PhDs can expect.

Defining Determinants of Fitness in Epithelial Development and Homeostasis

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.

Mechanisms of Loser Cell Elimination & Maintaining Epithelial Integrity

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 & Cancer

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.

Cell Competition & Mosaic Genetic Disease

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.

    Team

    Eleni Angelopoulou
    PhD Student
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    Andreea Constantinescu
    Lab Technician
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    Leonie Drakos
    Lab Technician
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    Room: 3.121

    Stephanie Ellis
    Group Leader
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    Almedina Hamza
    Master Student
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    Ameya Rakesh Khandekar
    PhD Student
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    Room: 3.121

    Michele Paganini
    Lab Technician
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    Clara Schimmer
    PhD Student
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    Sanskriti Sharma
    PhD Student
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    Selected Publications

    Stem cell progeny liaisons in regeneration.

    2021 Nature cell biology(9)
    PMID:  34475535

    Ellis Stephanie J, Fuchs Elaine

    Distinct modes of cell competition shape mammalian tissue morphogenesis.

    2019 Nature(7757)
    PMID:  31092920

    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.

    2016 Developmental cell(5)
    PMID:  27923121

    Goodwin Katharine, Ellis Stephanie J, Lostchuck Emily, Zulueta-Coarasa Teresa, Fernandez-Gonzalez Rodrigo, Tanentzapf Guy

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