General interests.We study how cells sense their environment and use this information to build and maintain tissues with specific form, size and function. We study how these mechanical inputs drive epigenetic reprogramming of epithelial cells into specific fates, and associated changes in the function and composition of surrounding stromal cells. Our ultimate goal is to dissect and interfere with these events to develop innovative strategies to tackle advanced tumors and metastases.
Tissue architecture, mechanical forces and cell shape are overarching, yet poorly understood regulators of cell behavior. Key elements of these signals are cell-extracellular matrix (ECM) and cell-cell adhesions, cell polarity and the mechanical-induced distortion of the cytoskeleton that keep individual cells and whole tissues in a certain shape.
We pioneered the notion that mechanical signals and cell shape are converted into biochemical responses by two related transcription factors, YAP and TAZ (Dupont et al., Nature 2011; Aragona et al., 2013; Panciera et al., 2017), that serve as central elements by which, in living systems, form dictates biological function. Our work is thus mainly centered on the biology of YAP/TAZ, two closely related transcriptional regulators playing essential functions in tissue regeneration and cancer (reviewed in Zanconato et al., 2016; Totaro et al., 2018). A central goal in our laboratory is to uncover the nature of cellular mechanotransduction systems in normal and pathologic contexts.
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- What are the mechanisms of mechanotransduction?
- Connecting mechanotransduction to immunity in tissue repair and cancer
- Connecting aging with mechanics and innate immunity
- Mechanics and neurodegeneration
- Linking mechanosignaling to epigenetics
- Metastasis as a developmental niche
Our approach to these goals entails both hypothesis-driven and data-driven investigations and combines an interdisciplinary set of expertise, ranging from molecular, biochemical and cell biological tools to animal models, tissue engineering, material science and "omic" approaches.