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Full NameProfessor Timothy O'Brien
Organisation:National University of Ireland Galway
- cell and developmental biology/regenerative medicine
- physiology and non-communicable disease
Postgrad Medical Specialties
- Emergency Medicine
- General Practice
- Public Health
- Clinical Trials
- Vascular Medicine
My research interests include the translation of basic research findings in stem cell biology to regenerative approaches to peripheral vascular disease and diabetic complications in partnership with industry and the health service. I have an active research group at REMEDI NUI Galway investigating the use of mesenchymal stromal cells and endothelial progenitor cells in vascular complications of diabetes mellitus.
I am Director of the GMP cell manufacturing facility at NUI Galway and have been a PI on gene therapy and cell therapy clinical trials in Galway. In addition to a laboratory-based programme, my research brings together the Galway HRB Clinical Research Facility, the Galway Blood and Tissue Establishment and the Centre for Cell Manufacturing Ireland for translational research in stem cells and gene therapy.
I am coordinator of 2 current EU funded projects; EU FP7 REDDSTAR which is developing and testing a novel stromal cell therapy to treat complications of diabetes mellitus (www.reddstar.eu) and the EU H2020 NEPHSTROM (www.nephstrom.eu), which will clinically validate a novel stromal cell therapy for the stabilization of progressive diabetic kidney disease.
The prevalence of diabetes is assuming pandemic proportions with an estimated global prevalence in excess of 500 million predicted by 2030. Diabetic complications are therefore major causes of global morbidity and mortality. Generally, the adverse effects of hyperglycemia are separated into macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (diabetic nephropathy, neuropathy, and retinopathy).
Mesenchymal Stromal Cells (MSC) have shown pleiotropic activities in vivo in animal models and in patients: they act as powerful immunosuppressive agents as well as secrete soluble factors that modify the pro-inflammatory cascade to promote tissue remodelling and cellular replacement. Thus MSC hold great promise for treatment of diseases and regeneration of injured tissues, such as in ischemic diseases, neurological disorders and also diabetes. Indeed there are currently greater than 480 clinical trials investigating the beneficial effects of MSC in a variety of disease conditions. Their exact mechanism of action is unknown but has been postulated to be related to the secretion of pro-angiogenic paracrine factors and their immunomodulatory and anti-inflammatory effects. Cross-talk also occurs between MSCs and endothelial cells as MSCs increase endothelial cell proliferation and migration, promoting early events of angiogenesis and decreasing endothelial cell monolayer permeability.
Project 1: Stem cell treatment for Diabetic Microvascular and Macrovascular Disease
This project will investigate the pre-clinical efficacy but also mechanism of action of a novel MSC cell type versus standard MSC therapy in diabetic microvascular and macrovascular disease. The ultimate aim of the project is to progress positive pre-clinical results to a clinical study in diabetic patients. Thus the project is expected to generate the data required for regulatory submission for a clinical study using the cell type with most positive pre-clinical results.
Project 2: Multimodality Advanced Therapy Medicinal Products for Limb Salvage in Diabetic Critical Limb Ischemia and Diabetic Foot Ulcers
This project will focus on next generation ATMPs with a specific emphasis on translation. Combinations of stem cells, genetic modification and biomaterials will be explored in pre-clinical models of diabetic and non-diabetic critical limb ischemia and in diabetic foot ulceration. The goal will be to bring these technologies to clinical trials.
The PhD candidate will also be involved in ongoing regenerative medicine clinical trials in my group.