Prof Tim O’Brien is recognized as an international expert on vascular wall gene delivery. Since his return to Ireland in July 2001, as Professor and Chairman of Medicine and Consultant Physician in Endocrinology and Metabolism at University College Hospital Galway, Prof. O’Brien has established a gene therapy research group, is Director of the Regenerative Medicine Institute (REMEDI), an SFI-funded CSET, and played a key role in establishment of the Clinical Research Facility.
Prof O’Brien received an honours MB BCh BAO degree from UCC in 1984. He went on to do an internship and general professional training at Cork University Hospital and 1 year as Registrar to Prof DJ O’Sullivan. He completed a two year residency in internal medicine at the Medical College of Wisconsin in Milwaukee in 1990 followed by a sub-specialty fellowship in Endocrinology and Metabolism at the Mayo Clinic in Rochester MN in 1992.
He was elected to Fellowship of the Royal Colleges of Physicians in Ireland and London in 1986 and 1987, respectively and to Fellowship of the American College of Physicians in 1995 and the American College of Endocrinology in 1996. He was awarded MD (1993) and PhD (1997) degrees from the National University of Ireland. He is board certified in Internal Medicine and Endocrinology and Metabolism in the USA and is a registered specialist in both specialties in Ireland.
Since returning to Ireland he has been a principal or co-applicant on grants worth in excess of €60 million. He has been a reviewer for 16 international journals, was a member of an American Heart Association Study Section, has acted as an invited reviewer on an NIH study section, and has been a reviewer for the Wellcome Trust and the Finnish Academy of Science. He served as associate editor of Endocrine Practice, the journal of the American College of Endocrinology from 1999-2006 and the e-journal of Translational Medicine.
Prof. O'Brien has published 155 original papers in peer-reviewed journals, 40 of these being review articles. He has contributed chapters to 9 books on topics relating to vascular gene transfer, and has been invited to present his research at 118 national and international scientific conferences. He is an author on 3 patent applications and 5 invention disclosures. He is the Director of the new MSc in regenerative medicine at NUI Galway with 15 students in the inaugural year and has supervised 4 of the 6 students who have graduated with PhD degrees from REMEDI in the past 18 months. He is co-founder of a spin out company, Procure Laboratories.
Since the initial funding of the CSET Prof O’Brien has played a leadership role in many initiatives which have substantially changed the academic profile at NUI Galway and in Ireland including: membership of the Advisory Science Council; chairing the Advisory Science Council’s task force on health research in Ireland; membership of Irish Medical Device Association task force on clinical trials; founding member and President of the Irish Society of Gene and Cell Therapy; membership of the Health Research Board; the evolution of the Dublin Molecular Medicine Centre to Molecular Medicine Ireland; establishment of the Irish Clinical Research Infrastructure Network (ICRIN); joint governance structures between NUI Galway and Galway University Hospitals including the development of a Memorandum of Understanding between the institutions; leading co-applicant on the Galway bid for a Clinical Research Facility; establishment of a GMP facility for cell and vector production; development of a clinician scientist training programme in Ireland; establishment of a new MSc and graduate education in Regenerative Medicine; drafting the College of Medicine research strategy with a major goal of recruiting future faculty with relevance to regenerative medicine; leveraging of faculty appointments to support the development of regenerative medicine; establishment of robust industrial partnerships based on strong interactions with the Industrial Development Agency and Enterprise Ireland; and the formal recognition of the importance of research to Galway University Hospital. In addition, Prof O’Brien has played a major role in the outreach and education activities of REMEDI including primary and secondary school programmes, public outreach and interaction with policy makers.
Gene therapy entails the delivery of new genetic information to cells so that their function is altered. By delivering specific genetic information, researchers have the ability to deliver a therapeutic effect by correcting an existing abnormality or providing cells with a new function, by influencing how the cell behaves, its function and how it responds to injury. One of the main difficulties with gene therapy is how to deliver this genetic material to cells. This is achieved by using vectors which carry the material into the cell. The most common vector is an engineered virus which has been rendered incapable of replication and is now carrying the gene product. A major focus of the gene therapy research in REMEDI is to develop safe and efficient vectors for the transfer of genetic material to cells. A variety of different viruses and non-viral means are being explored. A major part of gene therapy is the safe and successful delivery of a therapeutic gene. Viruses have the ability to overcome several obstacles to successful gene delivery. However a lot of research is required to understand the immune and cellular responses to these vectors. The gene therapy research at REMEDI will promote vector development focusing on the safe and effective use of Adenoviral, Lentiviral and Adeno Associated Viral vectors.
Adeno associated viral (AAV) vectors are smaller that Adenoviral vectors, however they allow stable gene expression over longer periods of time than adenoviral vectors and have a very good safety profile as they are not associated with disease in humans. AAV vectors are being used by REMEDI researchers to deliver therapeutic genes to the vasculature to treat cardiovascular disease, and ongoing research is determining the optimal serotype of AAV for vascular gene transfer. Adenoviral Vectors Adenoviral Vectors based on serotype 5 of the human adenovirus have been used in several clinical trials for therapeutic gene transfer in humans. The Viral vector is deleted in E1 and E3 genes rendering it replication incompetent, this allows it to act as an extremely efficient and safe vector for gene transfer to both dividing and non-dividing cells.
Understanding how the body’s immune system responds to transplanted cells and genes is critical in developing new therapeutic strategies. This programme aims to understand the mechanisms of host tolerance to delivered cells and genes.
The success of gene therapy relies largely on the availability of gene delivery vectors that confer therapeutic gene expression in target organs with minimal adverse affects on the host. The immunology programme at REMEDI is aimed at addressing the immunological consequences to the host of the use of viral vectors such as Adeno Associated Virus (AAV) vectors and Lentiviral vectors for therapeutic gene delivery.