Griffin Group

Disease-modulating regenerative therapies and biomarkers in diabetic kidney disease 

Chronic kidney disease occurs in over 30% of people with diabetes and, despite progress in medical care and pharmacotherapy, a high proportion of them continue to progressively lose kidney function over time. With colleagues at REMEDI, Saolta University Healthcare Group and collaborating institutions, my group is performing research related to the translation of mesenchymal stromal cell (MSC) and other disease-modulating regenerative therapies (DMRT) to the clinical challenge of progressive diabetic kidney disease (DKD). We have developed in vitro models of renal cell/MSC cross-talk, are active participants in an EU Horizon2020-funded Phase 1b/2a clinical trial of a novel MSC therapy for DKD associated with type 2 diabetes (www.nephstrom.eu) and are evaluating assays of inflammatory mediators and other DKD-associated that signatures that may serve as biomarkers of patient responsiveness to DMRT. 

Mesenchymal stem/stromal cells suppress T-helper 17 (Th17) differentiation of naïve and memory CD4+ T cells in a cyclooxygenase (COX)2/prostaglandin E2 (PGE2)-dependent manner. Adapted From: Duffy et al., Eur J Immunol 41:2840-51, 2011. 

Our work in this area has been funded to date by Science Foundation Ireland, the European Commission, the Irish Research Council and Abbott Laboratories.  

Collaborators that have contributed to the research are located at REMEDI; the NUI Galway Centre for Cell Manufacturing; the HRB Clinical Research Facility Galway; Orbsen Therapeutics Ltd, Galway; Maynooth University;    

Allogeneic corneal transplantation has been successfully used to restore sight to people with severe corneal disease for over 100 years. Although generally considered to have high success rates and to require low levels of immune suppressing therapy, a relatively high proportion of corneal transplants have one or more risk factors for acute rejection and, as a result, continue to have poor long-term graft survival. With colleagues in REMEDI and collaborators in leading European Centres, I have coordinated the EU FP7-funded consortium VISICORT (www.visicort.eu) which focusses on basic, clinical and translational research to improve the outcomes of high immunological risk corneal transplants. Among the collaborative research activities of the consortium have been: (a) Pre-clinical validation of an immunomodulatory mesenchymal stem/stromal cell (MSC) therapeutic protocol to reduce acute rejection in a high immunological risk model of corneal allo-transplantation. (b) Development of a regulator-approved bone marrow allo-MSC product and phase 1 clinical trial protocol for clinical translation of MSC therapy in high risk human corneal transplantation. (c) Creation of multi-centre European observational cohorts of corneal transplant recipients linked to a large biobank of biological samples from enrolled patients (VISICORT Foundation Biobank, https://visicort.eu/visicort-foundation-biobank/). (d) Extensive immunological profiling and transcriptomic/proteomic analyses of biological samples from the VISICORT patient cohorts. Ongoing work linked to the project includes clinical outcomes studies, new tissue analysis projects, sharing of biological samples with other researchers and exploration of novel immunological assays.         

Our work in this area has been funded to date by the European Commission and Science Foundation Ireland.  

Collaborators that have contributed to the research are located at REMEDI; the NUI Galway Centre for Cell Manufacturing Ireland; the Royal College of Surgeons in Ireland; Biostór Ireland Ltd., Orbsen Therapeutics Ltd., Galway; the University of Edinburgh, the University of Bristol and Fios Genomics Ltd. in the UK; INSERM and University of Nantes in France; Aarhus University Hospital and Aarhus University in Denmark; Charité University, Charité Research Organisation and Epimune GmbH in Berlin, Germany.

Clinical translational support for medical device technologies 

As a funded investigator and co-principal investigator of the CÚRAM SFI Research Centre for Medical Devices (http://www.curamdevices.ie/) since 2015, I have coordinated a multi-disciplinary research support platform focussed on supporting and facilitating the clinical translation of novel medical devices. Our research and innovation activities have included health economics, quality of life and discreet choice analysis; statistical methodologies and resources for device clinical investigations; regulatory pathways for medical devices and development of novel e-learning resources for medical device researchers. As CÚRAM begins its second phase of funding in 2021, an additional focus will be placed on clinical translational assessment and support of early-stage medical device research projects.  

Our work in this area has been funded by Science Foundation Ireland.  

Collaborators that have contributed to the research are located in CÚRAM; the HRB Clinical Research Facility Galway; the Health Economics and Policy Analysis Centre, NUI Galway; the School of Mathematics, Statistics and Applied Mathematics, NUI Galway; the School of Political Science and Sociology, NUI Galway; Galway University Hospitals; Clinical Research Development Ireland; University College Cork; BigTop Multimedia, Dublin and Aerogen Ltd., Galway.

As Scientific Director of the NUI Galway Flow Cytometry Core Facility (FCCF), I have had the opportunity to extensively apply cytometry and cell sorting protocols for use in my own research in the areas of Immunology, Regenerative Medicine and Kidney Disease, to work collaboratively with many colleagues and to bring new core research infrastructure to a wide range of NUI Galway researchers. Among the recently-acquired FCCF technology offerings are an Imagestream X Mark II imaging cytometer and a Northern Lights 3000 spectral cytometer with capacity for 24 colour analysis.  

Imaging flow cytometry demonstrating the cell-cell interactions between purified, fluorescently-labelled regulatory T cells (T-reg), CD4 effector T cells (CD4) and dendritic cells (DC).Adapted From: Cabral et al., Frontiers Immunol 2017 8:987. 

Funding for the NUI Galway flow cytometry core facility has been received from Science Foundation Ireland, the European Regional Development Fund and the Irish Government’s Programme for Research in Third Level Institutions, Cycle 5. 

Please see here for research publications.