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- Itoh Group | Cell Migration Research Group
Pia Pernille Søgaard
In my PhD project, I investigate the role of cell-matrix interactions in guiding epithelial morphogenesis. As an example of such morphogenesis we study HGF-induced tubulogenesis, which requires the epithelial cells to collectively invade into their surroundings. The transmembrane matrix metalloproteinase MT1-MMP is known to drive matrix degradation and invasion in this model and is furthermore involved in cellular invasion in a range of pathologies. Understanding the regulation of MT1-MMP during invasion is thus of great importance.
We have found that a signal from collagen, mediated by the the collagen-binding receptor tyrosine kinase, DDR1, plays a key role in the spatial regulation of MT1-MMP. Furthermore, DDR1 is required for epithelial morphogenesis in different 3D matrices. This role of DDR1 is not restricted to guiding MT1-MMP localisation, but furthermore affects cytoskeletal organisation and the ability of epithelial cells to establish apicobasal polarity in 3D environments.
This role of DDR1 in regulating cytoskeletal organisation appears to extend to its function in morphogenesis and lactogenic differentiation of mammary epithelial cells and may thus be an important signalling mechanism downstream of DDR1.
I am currently writing up my thesis and expect to graduate summer 2017.
Before joining Professor Yoshi Itoh's lab I completed my MSc in Molecular Biomedicine at University of Copenhagen. As part of my MSc I conducted 1.5 years on research in the lab of Professor John Couchman (Biotech Research and Innovation Centre, University of Copenhagen). In his lab I studied the role of a family of transmembrane heparan sulphate proteoglycans called syndecans in regulation of TRPC Ca2+-channels. Particularly I examined the importance of this regulation for keratinocyte differentiation as well as the conservation of the Ca2+-modulating function of syndecans in the neurons of C. Elegans.
Sandeep Gopal, Pernille Søgaard et al. (2015) Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels .J Cell Biol 2015 210:1199-1211.
2016: Prize for Best Talk at “28th meeting of the UK Cell Adhesion Society”, UCL, UK
2016: Best Poster Presentation Prize at “Metalloproteinases and their inhibitors: Beginning, past and future”, Oxford, UK
2015: Poster Presentation Prize at British Society for Matrix Biology (BSMB) meeting: “Location, Location, Location: the matrix and the microenvironment”, Oxford, UK
2015: Best Scientific Presentation award for oral presentation at “32nd Winter School on Proteinases and Inhibitors”, Tiers, Italy
MDCK cells in 3D collagen I culture
Green: apical marker GP135 Red: actin cytoskeleton Blue: nuclei Confocal image