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. 

Potential mechanisms of action of MSC therapeutic benefits in DKD. From: Hickson LJ et al., Kidney360, 2021.  

Our work in this area has been funded to date by the European Commission (Horizon 2020), the NUI Galway Hardiman Scholarship programme and the Irish Endocrine Society.  

Collaborators that have contributed to the research are located at the NUI Galway Centre for Cell Manufacturing; Galway University Hospitals Clinical Biochemistry Department; Orbsen Therapeutics Ltd, Galway; University College Dublin Conway Institute; the Mario Negri Institute in Bergamo, Italy, the University of Birmingham in the UK , Queen’s University Belfast in Northern Ireland, Leiden University Medical Centre in the Netherlands; Ludwig Maximilian University of Munich in Germany and the Mayo Clinic in Rochester, Minnesota and Jacksonville, Florida USA.   

Inflammatory monocytes and in chronic kidney disease 

Monocytes are circulating innate immune cells which are highly response to pathogen- and danger-associated molecular patterns, adhere to and transmigrate through inflamed endothelium and may differentiate into tissue macrophages and dendritic cells during acute and chronic disease. My group has investigated the monocyte repertoire during health, obesity, diabetes, chronic kidney disease (CKD) and cardiovascular disease. We have described novel subpopulations of intermediate monocytes distinguishable by mid- and high-level expression of the MHC II protein HLA-DR. In CKD we find that HLA-DRhi intermediate monocytes become increasingly more numerous in the blood as renal function declines and adhere strongly to activated endothelium. Our ongoing work is delving deeper into the functional characteristics of HLA-DRhi intermediate monocytes and other monocyte subpopulations in the blood and kidneys in people with CKD.    

Cell surface expression of HLA-DR by flow cytometry defines two subpopulations of the human intermediate monocyte subset. Adapted From: Connaughton EP, PhD thesis, 2015. 

Our work in this area has been funded to date by the Irish Government’s PRTLI5 programme, Science Foundation Ireland, the NUI Galway Hardiman Scholarship programme, Enterprise Ireland, Randox Teoranta and the Health Research Board/Wellcome Trust-funded Irish Clinical Academic Training (ICAT) programme.

Mesenchymal stem/stromal cell immunological properties and immune responses to allogeneic MSCs 

With REMEDI colleagues and other collaborators, my research group has had a longstanding interest in MSC-mediated immune modulation, the immunological responses to allogeneic MSCs and the implications of these phenomena for allogeneic (allo-)MSC therapies. Along with other researchers in this area, we have demonstrated that, in contrast to the original view of MSCs as being “non-immunogenic”, allo-MSCs elicit distinctive cellular (T-cell) and humoral (B-cell/antibody) donor-specific responses whether administered systemically or locally. Furthermore, under some circumstances, the anti-donor immune responses to allo-MSCs may be modulatory in nature and contribute directly to their potential therapeutic benefits. In the EU-funded translational projects, NEPHSTROM  and VISICORT , the immunogenicity and immune modulatory properties of clinical-grade MSCs are being tested in early phase clinical trials. Ongoing work in the laboratory is also addressing the direct interactions between human allo-MSCs and regulatory T-cells.  

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;    

Clinical translation of allogeneic MSC therapy for high-risk corneal transplantation 

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.         

Human corneal transplant. Top Right: Clinical-grade manufacture of allogeneic bone marrow MSCs at NUI Galway’s Centre for Cell Manufacturing Ireland. Bottom: Cryopreserved allogeneic MSC, manufactured in a Quantum CES hollow fibre bioreactor potently inhibit proliferation of human CD4+ T-cells from peripheral blood mononuclear cells (PBMC).  

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.

Vasculitis and Rare Kidney Disease registry and biobank 

Since 2014, I have been a partner of the Rare Kidney Disease Registry (RKD) and Biobank, a national resource for vasculitis and other rare diseases affecting the kidneys that is coordinated by Prof. Mark Little of the Trinity Kidney Health Centre, School of Medicine, Trinity College Dublin (https://www.tcd.ie/medicine/thkc/research/rare.php). With clinical colleagues and specialist trainees in the Galway University Hospitals Nephrology Services and clinical research nurses in the HRB CRF Galway, I oversee enrolment of patients in our region to the RKD Registry and participate in collaborative projects linked to the Registry and Biobank.

Flow Cytometry and Cell Sorting 

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.


  • European Commission Horizon 2020
  • NUI Galway Hardiman Scholarship programme
  • Irish Endocrine Society
  • Irish Government’s PRTLI5 programme
  • Science Foundation Ireland (SFI)
  • Enterprise Ireland (EI)
  • Randox Teoranta
  • Health Research Board (HRB)-Wellcome Trust-funded Irish Clinical Academic Training
  • (ICAT) programme
  • Irish Research Council (IRC)
  • Abbott Laboratories