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Dr Peter Lackie
CELL BIOLOGY OF MUCOSAL EPITHELIA
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CD44 (green) in migrating epithelial cells moving to repair damage (to right of picture), cell nuclei in orange.
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Epithelial cells of the mucosal surfaces form the primary barrier between the internal and external environments. Damage? as seen for example in asthma? results in loss of barrier function, increasing the vulnerability of the underlying tissues and the likelihood of adverse long-term disease. To restore the protective barrier as quickly as possible, epithelial cells dedifferentiate, alter their cell-cell and cell-matrix adhesion and migrate to cover the damaged areas. During this process epithelial cells are highly "activated" and become an important local source of pro-inflammatory mediators, growth factors and proteases. Research in the group focuses on this epithelial cell activation and migration following damage. We are examining the function of complexes of cell surface molecules in epithelial repair, particularly in respiratory tract and the conjunctiva of the eye, focussing on three
aspects:
- Cell adhesion molecules are essential for intact cells to sense damage and then to implement the appropriate responses. The expression and localisation of the cell adhesion molecule CD44 is altered early in the repair process. The function of CD44 in epithelial repair is being examined. CD44 (green) in migrating epithelial cells moving to repair damage (to right of picture), cell nuclei in orange.
- Cell surface matrix metalloendoproteinase (MMP) activity is increasingly recognized as a key regulator of cell adhesion and cell migration during repair and at the cell surface it can be functionally associated with CD44.
- Carbohydrate residues on cell surface proteins are used to alter the properties of individual proteins and also regulate interactions between cells. Work in the group has shown that specific carbohydrates are important in regulating adhesion and migration during epithelial repair.
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Migration of airway epithelial cells labelled with a green fluorescent protein tracked by time lapse microscopy over a 6 hour period, red markers indicate the track of the cells.
The studies of epithelial repair in the group use models of human epithelia including cultures established directly from clinical samples. A mixture of cell and molecular biology techniques are applied including, electron-, confocal- and time-lapse-microscopy, flow cytometry, RT-PCR, cell transfection and immunoblotting. By understanding the basic cell biology of mucosal epithelia, we aim to determine the importance of epithelial dysregulation in diseases such as asthma and conjunctivitis.
For further details
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here Email: p.m.lackie@soton.ac.uk
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