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School Research Profile

Dr. Michael Freeley – A Research Profile

 Dr Michael Freeley

Dr Michael Freeley is a Lecturer in Biomedical Sciences in the School of Biotechnology and Programme Chair of the M.Sc. in Biomedical Diagnostics. He joined DCU in September 2016 from Trinity College Dublin (TCD). His research focuses on the cell biology of the T-cell immune response, particularly the genes and signalling pathways that T-cells use for migration and activation. The translational aspect of this research aims to understand how these pathways may be manipulated for the treatment of autoimmune/inflammatory diseases, infectious diseases and cancer (immunotherapy).  Indeed, several therapeutic drugs that directly target T-cell signalling pathways are now clinically-approved for the treatment of many of these diseases and conditions.

Michael’s story

Michael’s scientific career began in DCU where he graduated with a first-class honours degree in Biotechnology in 1999.  It was during his third year undergraduate INTRA placement and final year research project with Elan Pharmaceutical Technologies where he developed his passion for scientific research. Michael then undertook a PhD in Biochemistry and Immunology in the Royal College of Surgeons in Ireland (RCSI) under the supervision of Dr Aideen Long.  His thesis investigated the signalling pathways that regulate the Protein Kinase C (PKC) family of enzymes in T-cells. This research led to the novel discovery that PKC θ is inducibly phosphorylated on Ser-695 in response to T-cell activation [1], a finding that has since been verified by several other groups using mass spectrometry and immunoblotting. PKC θ is a positive regulator of T-cell activation and inflammatory cytokine production and a number of pharmacological inhibitors that target this kinase have been developed recently by the pharmaceutical industry to inhibit T-cell signalling in inflammatory/autoimmune diseases.  Michael then undertook post-doctoral research in RCSI for 18 months. It was during this period that Michael was awarded a travel grant by Enterprise Ireland that enabled him to work in the laboratory of Prof Gottfried Baier in Innsbruck, Austria for four months (Prof Baier discovered and cloned the gene for PKC θ in T-cells in 1993). This successful collaboration between Michael and Prof Baier’s group resulted in the publication of a commentary article on PKC θ in Science magazine in 2006 [2].     

In 2005 Michael moved to the Institute of Molecular Medicine in TCD where he was employed as a Research Fellow (2004-2015) and was subsequently awarded a Senior Research Fellowship (2015). During this time he co-ordinated the HRB-funded PhD in Molecular Medicine programme (2008-2012) and co-ordinated/lectured on the M.Sc. in Molecular Medicine programme (2013-2016).  His research in TCD focused on the molecular mechanisms of T-cell activation and migration using state-of-the-art approaches including RNA interference (RNAi), screening of RNAi libaries and High Content Image Analysis.  RNAi is a powerful tool for silencing of gene expression, as it enables loss-of-function studies to be carried out in a highly-specific manner [3], whereas screening of RNAi libraries has made it possible to identify all genes involved in any cellular process in an unbiased manner [4]. Furthermore, High Content Image Analysis utilises automated microscopy to rapidly acquire and analyse thousands of cells in a single well.  Michael’s interest in utilising RNAi and library screening for his research was initially made possible by a travel award from the Ulysses-funded ‘France-Ireland Exchange Scheme’ which enabled him to work in the laboratory of Dr Frederique Michel at the Pasteur Institute (Paris) and learn the technique of RNAi delivery to T-cell lines. He subsequently developed an improved method for delivering RNAi to primary human T-cells (which are widely known as ‘hard-to-transfect’) [5], a finding that directly led to his discovery that the actin-bundling protein L-plastin is a key regulator of motility in primary human T-cells [6].

Michael has also led a collaborative project with the international life science company Dharmacon (now part of GE Healthcare) where he performed the first RNAi library screens in primary human T-cells using their proprietary self-delivering RNAi technology [7; webinar available at http://labroots.com/webinar/id/91]. In addition, he developed a High Content Image Analysis assay to analyse the morphology of migrating T-cells and its use in downstream applications including screening of RNAi libraries [8].  For that study [8], Michael was awarded the High Content Analysis prize by GE Healthcare in 2010.  In addition to working with several partners from Industry in collaborative projects, he has carried out contract research for a pharmaceutical company to screen small molecule drugs to evaluate their anti-inflammatory potential in in-vitro T-cell assays. Since joining DCU in September 2016, Michael is particularly interested in hearing from academic, clinical and industrial organisations who would like to leverage his expertise in T-cells, immunology and cell biology/cell signalling for research collaborations, grant applications and contract research.

 Contact details: Michael Freeley, X225, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9. Telephone: 353-1-7005961. Email: michael.freeley@dcu.ie.

 Selected publications

[1] Freeley M, Volkov Y, Kelleher D, Long A. (2005). Stimulus-induced phosphorylation of PKC q at the C-terminal hydrophobic-motif in human T lymphocytes. Biochemical and Biophysical Research Communications 334(2):619-30.

[2] Gruber T, Freeley M, Thuille N, Heit I, Shaw S, Long A, Baier G. (2006) Comment on "PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation". Science 312(5770):55.

[3] Freeley M and Long A. (2013) Advances in siRNA delivery to T cells: potential clinical applications for inflammatory disease, cancer and infection. Biochemical Journal 455(2): 133-147.

[4] John S, Freeley M, Long A and Frasier I. (2014) RNAi screening in cells of the immune system: challenges and opportunities. Frontiers in RNAi. 1: 144-177.

[5] Freeley M and Long A. (2013) The Two Hit Hypothesis: An Improved Method for siRNA Mediated Gene Silencing in Stimulated Primary Human T Cells. Journal of Immunological Methods 396(1-2): 116.

[6] Freeley M, O’Dowd F, Paul T, Kashanin D, Davies A, Kelleher D, Long A. (2012). L-plastin regulates polarisation and migration in chemokine-stimulated human T lymphocytes. Journal of Immunology 188(12): 6357-70.

[7] Freeley M, Bakos G, Davies A, Kelleher D, Long A, Dunican DJ. (2010). A High Content Analysis Toolbox Permits Dissection of Diverse Signalling Pathways for T lymphocyte Migration. Journal of Biomolecular Screening 15(5):541-55.

[8] Freeley M, Derrick E, Dempsey E, Hoff A, DaviesA, LeakeD, Vermeulen A, KelleherD and LongA. (2015) RNAi screening with self-delivering, synthetic siRNAs for identification of genes that regulate primary human T cell migration. Journal of Biomolecular Screening 20(8): 943-956.

 


11th April, 2017
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