Director of REMEDI
Development of gene and cell therapy approaches to vascular disease with a special focus on the augmentation of nitric oxide bioavailability.
Researcher in
Professor O'Brien established the Regenerative Medicine Institute at NUI, Galway (REMEDI). The focus of the Institute is to exploit the synergies between the technologies of gene delivery and stem cell biology to promote organ regeneration and repair. The principal initial disease targets of the Institute are ischaemic cardiovascular disease and osteoarthritis.
NO bioavailability
NO bioavailability is diminished in a variety of vascular disease states such as hypertension, hyperlipidemia and diabetic wounds. The PI is interested in a therapeutic approach to these disorders using gene and or cell therapy. The gene therapy approach has focused on targeted expression of nitric oxide isoforms in the diseased vessel site and the use of endothelial progenitor cells as a gene deliver system. The PI also has an interest in the pathogenesis of diabetic vascular disease including the role of endothelial progenitor cel dysfunction.
2004-present
Director of the Regenerative Medicine Institute, NUIG and GUH
2001- present
Professor and Head of Medicine, Consultant Endocrinologist
NUIG and Galway University Hospital
1995-2001
Consultant
Division of Endocrinology, Nutrition and Metabolism, Mayo Clinic, Rochester, MN
1999-2001
Associate Professor of Medicine
Mayo Foundation, Rochester, MN
1995-1999
Assistant Professor of Medicine
Mayo Graduate School of Medicine, Rochester, MN
1993-1994
Postdoctoral Fellow
Gladstone Institute of Cardiovascular Disease, San Francisco
1993-1994
Assistant Clinical Professor of Medicine
University of California, San Francisco
1990-1992
Fellow in Endocrinology and Metabolism
Mayo Graduate School of Medicine, Rochester, MN
1988-1990
Resident in Internal Medicine
Medical College of Wisconsin, Milwaukee, WI
1984-1988
Resident in Internal Medicine
Cork Regional Hospital
1996
PhD
National University of Ireland, Cork
1990
MD
National University of Ireland, Cork
1987
MRCP (UK)
Royal College of Physicians, UK
1986
MRCPI Part 2
Royal College of Physicians of Ireland
1986
MRCPI Part 1
Royal College of Physicians of Ireland
1978
College Scholar; University College Cork
1988
Ainsworth Scholarship; University College Cork
1991-1992
WL Stephenson Fellowship in Clinical Nutrition; Mayo Graduate School of Medicine
1993-1994
Mayo Foundation Scholar; Mayo Graduate School of Medicine
1993
Sprague Award for Excellence in Clinical Medicine; Division of Endocrinology and Metabolism, Mayo Clinic
1997
Outstanding Poster Presentation. Internal Medicine Research Activities Forum, Mayo Clinic
1998
Young Investigator Award. Vascular and Myocardial Aspects of Ischemic Heart Disease. American Heart Association.
1998
Mayo Clinic Internal Medicine Research Award: Adipocyte Macrophage Colony Stimulating Factor (MCSF) Is a mediator of adipose tissue growth.
2005
Stokes Medal, Irish Cardiac Society
2007
Nordisk Lecture, Irish Endocrine Society
2008
48th Graves lecture of the Royal academy of Medicine in Ireland
1.Cooney, R, Hynes, SO, Sharif, F, Howard, O’Brien, T. Effect of gene delivery of NOS isoforms on intimal hyperplasia and endothelial regeneration after balloon injury. Gene Therapy(2007) 14, 396-404.
2.McCabe C, O’Brien T. Beta cell cytoprotection using lentiviral vector-based iNOS-specific shRNA delivery. Biochem Biophys Res Commun. 2007 May 25;357(1):75-80. Epub 2007 Mar 28.
3.Reeve, J, Stenson-Cox, C, O’Doherty, A, Porn-Ares, I, Ares, M, O’Brien, T, Samali, A. OxLDL-induced gene expression patterns in CASMC are mimicked in apoE-/-mice aortas. Biochemical and Biophysical Research Communications 356 (3) 681-6, 2007.
4.Reeve JL, Szegezdi E, Logue SE, Chonaighle TN, O’Brien T, Ritter T, Samali A. Distinct mechanisms of cardiomyocyte apoptosis induced by doxorubicin and hypoxia converge on mitochondria and are inhibited by Bcl-xL. J Cell Mol Med. 2007 May-Jun;11(3):509-20.
5.Dwyer RM, Potter-Beirne SM, Harrington KA, Lowery AJ, Hennessy E, Murphy JM, Barry FP, O’Brien T, Kerin MJ. Monocyte Chemotactic Protein-1 (MCP-1) secreted by primary breast tumors stimulates migration of Mesenchymal Stem Cells (MSCs). Clinical Cancer Research (2007) 13 (17): 5020-5027.
6.Stender S, Murphy M, O’Brien T, Stengaard C, Ulrich-Vinther M, Soballe K, Barry F. Adeno-associated viral vector transduction of human mesenchymal stem cells. Eur Cell Mater. 2007 May 31;13:93-9; discussion 99.
7.Rao, VP, Branzoli SE, Miyagi N, O’Brien, T, Tazelaar HD, Russell SJ, McGregor CG. Recombinant adenoviral gene transfer does not affect cardiac allograft vasculopathy. J Heart Lung Transplant. 2007 Dec:26(12):1281-5.
8.S. Sen, S. Conroy, S.O. Hynes, J. McMahon, A. O'Doherty, Y. Akhtar, T. Adegbola, C.E. Connolly, S. Sultan, F. Barry, Z.S. Katusic, T. O'Brien. Gene delivery to the vasculature mediated by low-titre adeno-associated virus serotypes 1 and 5. Journal Gene Medicine. 2008 Feb:10(2):143-51.
9.Holohan, C, Szegezdi, E, Ritter, T, O’Brien, T, Samali, A. Cytokine-induced Beta-Cell Apoptosis is no-dependent, mitochondria-mediated and inhibited by BCL-XL. Journal of Cellular and Molecular Medicine. 2008 Mar-Apr;12(2):591-606. Epub 2007 Dec 10
10.Breen, A, Dockery, P, O’Brien, T, Pandit, A. Fibrin scaffold promotes adenoviral gene transfer and controlled vector delivery. J Biomed Mater Res A. 2008 May 8.
11.Breen, A, Dockery, P, O’Brien, T, Pandit, A.The use of therapeutic gene eNOS delivered via a fibrin scaffold enhances wound healing in a compromised wound model. Biomaterials 2008 Jul;29(21):3143-51.
12.Rooney, G, Moran, C, McMahon, S, Ritter, T, Maenz, M, Flugel, A, Dockery,P, O’Brien, T, Howard, L, Windebank, T, Barry, F. Gene- Modified Mesenchymal Stem Cells Express Functionally Active Nerve Growth Factor on an Engineered Poly Lactic Glycolic Acid (PLGA) Substrate. Tissue Eng Part A. 2008 Apr 11.
13.Flynn, A, O’Brien, T. Alferminogene tadenovec, an angiogenic FGF4 gene therapy for coronary artery disease. IDrugs. 2008 Apr;11(4):283-93.
14.Mylotte, L, Duffy, A, Murphy, M, O’Brien, T, Samali, A, Barry, F, Szegezedi, E. Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment. Stem Cells. 2008 May;26(5):1325-36. Epub 2008 Feb 28
Review Articles 2007-08
1.Liew, A, McDermott, J.H, Barry, F, O’Brien, T. Endothelial progenitor cells for the treatment of diabetic vasculopathy: panacea or pandora’s box? Diabetes Obes Metab. 2007 Sep 6;.
2.Gaffney, MM, Hynes, SO, Barry, F, O’Brien, T. Cardiovascular gene therapy: current status and therapeutic potential. British journal of Pharmacology (2007) 152, 175-188. This article was downloaded (either in pdf or html form) a total of 1,857 times by online subscribers over the 3 months post-publication, the largest number of downloads of all the papers in this issue of BJP.
3.Flynn A, Barry F, O’Brien T. UC-blood derived mesenchymal stromal cells: an overview. Cytotherapy 9(8):7127-726 Oct 2007.
4.McCabe C, O’Brien T. The rational design of beta cell cytoprotective gene transfer strategies: targeting deleterious iNOS expression. Mol Biotechnol 37(1):33-47 Sep 2007.
5. Flynn, A, O’Brien, T. Alferminogene Tadenovac, an angiogenic FGF4 gene therapy for coronary artery disease. IDrugs 2008 11 (4): © The Thomson Corporation ISSN 1369-7056.
Professional memberships:
- American College of Physicians
- American Medical Association
- American Diabetes Association
- Royal College of Physicians of Ireland
- Arteriosclerosis Council of the American Heart Association
- American Society of Gene Therapy
- Editorial Board of Endocrine Practice and the Journal of Translational Medicine
- Editor-in-Chief of Stem Cell Research & Therapy - http://www.stemcellres.com