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Full NameProfessor Matthew Griffin
Department:School of Medicine
Organisation:National University of Ireland Galway
- infectious disease and the immune system
- cell and developmental biology/regenerative medicine
- Clinical Trials
- Infectious diseases
- Vascular Medicine
My research has focussed for the past 20 years on basic and translational studies of the immune system and inflammation - particularly their contributions to the pathophysiology of kidney disease and transplantation (e.g. Kidney Int. 2007,71:619-628; J Am Soc Nephrol, 21: 1987-1997,2010; J Am Soc Nephrol, 23:194-203,2012). Since returning to Ireland in 2008, I have directed these interests to the field of regenerative medicine and allogeneic cell therapies with an emphasis on the immunomodulatory properties of mesenchymal stromal cells/MSC (e.g. Am J Physiol Renal Physiol 307:F1412-26,2016; Stem Cells, 31:2033-41,2014; Immunol Cell Biol, 96: 536–548,2018; Frontiers Immunol, Nov 20;9:2666,2018).
With colleagues and collaborators in REMEDI and at several leading centres in Europe and the US, my group has recently been closely involved in translating allogeneic cell therapies to the clinic through regulator-approved early phase clinical trials (see www.visicort.eu and www.nephstrom.eu) as well as biomarker and immune profiling studies (e.g. Immunol Cell Biol, 96: 675-784,2018; Frontiers Immunol, Dec 6;9:2845,2018; Clin Chem Lab Med, ePub, Sept 15,2018). We have strong expertise in flow cytometry, primary immune cell isolation and culture, immunoassays, pre-clinical models and histology/immunohistochemistry. We also have extensive experience in patient-oriented research.
Project Title: Mesenchymal stromal cell-enhanced regulatory T-cell therapy for inflammatory complications of diabetes
Recent work in my laboratory has focussed on the interactions between mesenchymal stromal cells (MSC) and regulatory T-cells (T-reg). Importantly, T-reg are CD4+ T-cells which are an essential component of the regulatory arm of the immune system - preventing widespread autoimmunity; participating in the resolution of inflammation and contributing to immunological tolerance in the setting of transplantation and cancer. Our experiments to date, using primary human T-reg and MSC, have allowed us to consistently identify multiple T-reg subpopulations in human blood and lymph node samples; perform T-reg culture expansion from small numbers of purified primary cells and demonstrate the potential for co-culture with allogeneic MSC to enhance the yield of primary T-reg in expansion cultures. Along with this, we have observed that adult patients with chronic kidney disease have similar circulating numbers of T-reg to healthy adults but have alterations to the repertoire of T-reg subpopulations that could negatively impact their ability to infiltrate inflamed tissue and mediate anti-inflammatory/pro-regenerative effects. Based on this, I am very interested in recruiting a clinician investigator trainee to the group to pursue a project that will test the following hypothesis:
“Ex vivo-expanded human regulatory T-cell subpopulations are conditioned by allogeneic mesenchymal stromal cells to mediate enhanced anti-inflammatory effects in the setting of diabetes”
Methodology and experimental design for the project will include patient and healthy volunteer recruitment and sampling; cell purification and culture expansion techniques; multi-colour flow cytometry; functional immune cell assays and data analysis approaches. I also envisage building a programme around the project that will include training in GMP-grade cell manufacturing/clinical trials; collaboration and additional training opportunities at ICAT supervisor-led laboratories in other Irish universities and collaborations with international experts in regenerative medicine and immunology.