Lackie, Peter - University of Southampton

研究领域

Epithelial cells lining the airway provide many essential functions. They are an integral part of the innate immune defence system acting as a barrier to infection and helping to provide immune surveillance. They produce mucus and ciliated cells power the mucociliary escalator. Maintaining the integrity and function of the airway epithelium is essential for life. Dr Lackie’s research focuses on three aspects of this. 1. Airway epithelial repair – role of glycoconjugates When the airway epithelium is damaged, effective and timely repair is important. Epithelial damage, either due to excessive insult or ineffective repair has long been recognised as a characteristic of asthma. Surface glycoconjugates on epithelial cells are very important modulators of interactions between cells and for cells interacting with their substrate. Studies using lectins that very specifically block interactions though certain glycoconjugates have shown that repair, as assayed using a scratch wounding model is particularly dependent on maintaining interactions through fucose containing glycoconjugates. 2. Ciliary function – ciliary dyskinesia and interactions with bacteria Cilia lining the epithelium of the respiratory tract clear mucus containing bacteria and particles by coordinated beating (image 1). This acts as a defence against infection. Southampton is one of 3 national centres for the diagnosis of Primary Ciliary Dyskinesia (PCD).People with PCD are born with a defect which prevents the cilia from beating normally, resulting in repeated chest infections and symptoms that may include a chronic nasal discharge, chronic sinusitis, glue ear and a wet cough. Because the embryonic nodal cilium is often affected, 50% of people with PCD have mirroring of their visceral organs (situs inversus). A mouse model of PCD showing situs inversus based on a mutation in a heavy chain dynein gene- Dnahc11- has been characterized. Using live cell imaging of cilia and transmission electron microscopy to examine the structure of the cilia this has been shown to have a phenotype similar to PCD patients with mutations in the equivalent human dynein gene DNAH11. As well as mutations in cilial genes cilial dysfunction can be caused by respiratory tract infection. Investigations of an alpha 1,6 binding lectin from Pseudomonas aeruginosa – a very common respiratory pathogen- have shown by electron microscopy that this lectin binds to cilia and using high speed video analysis the speed of cilial beating has been shown to be reduced by this lectin. 3. Epithelial function- Protocadherin-1 (PCDH1) in asthma Three PCDH1 gene variants have been linked to bronchial hyperreactivity (BHR) and asthma. PCDH1 is expressed in differentiated airway epithelial cells. As part of a collaborative project between Dr Koppelman from Groningen University and Drs Holloway and Lackie from Southampton the differential sub-cellular localisation of PCDH1 in airway epithelial cells is being investigated.

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Comparison of miRNA profiling during airway epithelial repair in undifferentiated and differentiated cells in vitro - Langwinski, Wojciech, Narozna, Beata, Lackie, Peter M., Holloway, John W. and Szczepankiewicz, Aleksandra Published:2016Publication:Journal of Applied GeneticsPage Range:1-8doi:10.1007/s13353-016-0370-5 Protocadherin-1 localization and cell-adhesion function in airway epithelial cells in asthma - Faura Tellez, Grissel, Willemse, Brigitte W.M., Brouwer, Uilke, Nijboer-Brinksma, Susan, Vandepoele, Karl, Noordhoek, Jacobien A., Heijink, Irene, de Vries, Maaike, Smithers, Natalie P., Postma, Dirkje S., Timens, Wim, Wiffen, Laura, van Roy, Frans, Holloway, John W, Lackie, Peter M, Nawijn, Martijn C., Koppelman, Gerard H. and , Published:2016Publication:PLoS ONEVolume:11, (10)Page Range:1-21doi:10.1371/journal.pone.0163967PMID:27701444 Selective killing of cells triggered by their mRNA signature in the presence of smart nanoparticles - Heuer-Jungemann, Amelie, El-Sagheer, Afaf H., Lackie, Peter M., Brown, Tom and Kanaras, Antonios G. Published:2016Publication:NanoscaleVolume:8, (38)Page Range:16857-16861doi:10.1039/c6nr06154k Primary air–liquid interface culture of nasal epithelium for nasal drug delivery - Ong, Hui Xin, Jackson, Claire L., Cole, Janice L., Lackie, Peter M., Traini, Daniela, Young, Paul M., Lucas, Jane and Conway, Joy Published:2016Publication:Molecular PharmaceuticsVolume:13, (7)Page Range:2242-2252doi:10.1021/acs.molpharmaceut.5b00852