Examining the immunomodulatory properties of mesenchymal stromal cells in health and disease
We seek a PhD candidate of outstanding ability to join a developing and active research team at The University of Birmingham led by Dr Helen McGettrick. Our research concentrates on the concept that changes in the characteristics of the tissue and/or circulating leukocytes are key in the switch from self-limiting to persistent inflammation as seen in e.g. rheumatoid arthritis. The focus of our research is to develop a more complete understanding of the pathways regulating leukocyte entry and exit from inflamed tissue in health and disease.
Mesenchymal stromal cells (MSC) have immunomodulatory capabilities. They display distinct spatial identities that govern their behaviour and allow them to establish tissue-specific ‘address-codes’ . It is these address-codes that actively regulate the recruitment of leukocytes to inflamed sites and their subsequent behaviour (reviewed ). MSC achieve these effects, in part, by conversing with neighbouring vascular endothelial cells (EC) to influence their ability to support leukocyte adhesion . Indeed, we have previously reported that healthy dermal fibroblasts and mesenchymal stem cells potently down-regulate the responsiveness of EC to cytokines, suppressing leukocyte recruitment in an IL-6 and TGF- dependent manner [3, 4]. In contrast, we have shown that rheumatoid synovial fibroblasts activate EC to inappropriately recruit leukocytes [3, 5], whilst simultaneously blocking leukocyte apoptosis . Thus MSC are capable of generating and supporting persistent infiltrates in disease conditions. Consequently, each inflammatory response is contextual, defined by the phenotype of the MSC at the site in question. Understanding the pathways influencing MSC function has potential for development of therapeutic strategies that mimic the actions of 'healthy' MSC or inhibit their pathogenic transformation, to manipulate inflammatory responses in disease.
The project will be based on unique multi-cellular in vitro models that incorporate primary human MSC and endothelial cells, with the view to applying findings to in vivo pre-clinical models of inflammation and/or the generation of in silico simulations as required. The student will be integrated into the multidisciplinary Leukocyte Trafficking Research Group at the University of Birmingham (www.birmingham.ac.uk/leukocyte-trafficking). We collaborate closely with research groups in the Centre for Translational Inflammation Research located within University Hospital Birmingham and the Centre for Cardiovascular Sciences, as well as members of The Systems Science for Health initiative (http://www.birmingham.ac.uk/research/activity/ssfh/index.aspx).
To apply please submit your CV and a covering letter/e-mail.
Applications are invited from self-funding applicants only. Overseas applicants will need to meet the UoB English requirements which are IELTS of 7.0 overall with no less than 6.5 in any band or Pearson Academic test.
1 Parsonage et al. Trends Immunol 2005;26:150-6.
2 McGettrick et al. J Leukoc Biol 2012.
3 McGettrick et al. Eur J Immunol 2009;39:98-107.
4 Luu et al. STEM CELLS 2013;31:2690-702.
5 Lally et al. Arthritis Rheum 2005;52:3460-649.
6 Filer et al. Arthritis & Rheumatism 54(7):2096-108, 2006.
How good is research at University of Birmingham in Clinical Medicine?
FTE Category A staff submitted: 164.15
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