Bryan Conway Raine Award Winner 2008
1. Title and place of work and what you are doing now? 
MRC Clinician Scientist University of Edinburgh and Honorary Consultant Nephrologist, Edinburgh Royal Infirmary
2. The work that led up to the Raine Award?
During my PhD (2000-2003) I employed a combinatorial approach to investigate the genetic susceptibility to diabetic kidney disease. Firstly, colleagues in University College Dublin had determined up to 200 genes that were dysregulated in mesangial cells exposed to high glucose and hence were potential novel candidate genes for conferring susceptibility to diabetic nephropathy (DN). We then cross-linked these genes with regions of the genome that were linked to DN in family linkage studies, and found that one gene up-regulated in high glucose called caldesmon was located on chromosome 7q, in a region previously linked to DN. I then conducted a comprehensive search for polymorphisms in the gene in the Irish population and found that a polymorphism in the promoter region was associated with DN in a case-control study.
3. What/who inspired the work?
The inspiration for my research was Prof Peter Maxwell, who has set-up a flourishing Renal Research Group in Belfast. Peter was an excellent mentor, always available for help and encouragement, while allowing plenty of opportunity for pursuing individual directions. I was lucky to be supported by the Northern Ireland Kidney Research Fund and while there were a number of potential projects that I could have chosen, but I opted for research into diabetic nephropathy as it is the most common cause of end-stage kidney disease in the UK. Fortuitously at that time Dr Damian Fogarty had secured funding for consumables from the Juvenile Diabetes Research Foundation. I consider that while the Raine award was credited to me individually, in reality it reflects the dedication of a long line of researchers in Belfast who laid the foundations for and assisted me with my research.
4. What did winning the Raine Award mean to you?
The Raine Award has had a major impact on my research career in two ways. Firstly, I was surprised and thrilled to receive the award and it both inspired me and gave me confidence to pursue a career in clinical academia. Secondly, it is pride of place in my CV and I hope that it will assist me with future grant and fellowship applications.
5. How has career progressed since you won the Raine Award?
I was lucky enough to be awarded a Clinician Scientist Fellowship by the MRC in 2007 and I am currently coming towards the end of my fellowship in the Centre for Inflammation Research in the University of Edinburgh. I have changed the nature of my research from genetics to inflammatory cell biology and animal models, but I am still focused on diabetic nephropathy. I also have an additional interest in the pathophysiology of the metabolic syndrome as it underpins the dramatic increase in DN over the past couple of decades. The Clinician Scientist Fellowship has allowed me protected research time to set up my new research group and provided resources such as consumables and an excellent technician who keeps me right with the day-to-day running of the lab! I also spend 20% of my time as an Honorary Nephrologist in the Edinburgh Royal Infirmary, where my clinical colleagues have been very flexible in allowing me to move in and out of clinical service as required to maintain my clinical acumen.
6. What are the implications of your research for clinical practice?
As yet my research has not impacted significantly on clinical practice. While the polymorphism in the caldesmon gene may confer susceptibility to diabetic nephropathy, it is likely to be one of a large number of such polymorphisms that promote disease, each conferring a small risk of disease. Therefore it is not likely to be useful in predicting which patients with diabetes are at risk for nephropathy. However my colleagues in Belfast are participating in a multinational project to perform a genome-wide screen for polymorphisms that predispose to nephropathy and the early results look promising. While prediction of an individuals risk of nephropathy will remain difficult, such screens are likely to identify genes that have not previously been known to contribute to diabetic kidney disease and hence provide novel therapeutic targets.
7. What is your proudest accomplishment?
I think that both the Raine award and attaining the Clinician Scientist Fellowship are the highlights of my career thus far. I was also delighted to be awarded best scientific abstract at the European Renal Association/European Dialysis and Transplantation Association Annual Meeting while I was a PhD student which was a big deal for me at the time.
8. What do you think is the most pressing problem in nephrology today?
From a clinical perspective it is to develop systems of working practice that will enable most efficient use of increasingly scarce NHS resources to deliver optimal care to the ever expanding population of patients with CKD.
From a scientific perspective we have done very well in our understanding and management of immunological renal disorders, acute rejection and many single gene disorders. However we have still very limited knowledge of and therapeutic agents for the most common problems such as acute kidney injury, diabetic nephropathy, progressive CKD, and chronic allograft nephropathy. Clinical and basic scientists need to collaborate to make the most of the revolution in genomics/proteomics in order to expand our knowledge of the pathophysiology of such disorders and translate these findings into new therapeutic modalities.
9. What advice do you have for junior trainees?
Work hard, but above all try to develop your career in ways that you find fulfilling. Develop a special interest, be it in a particular field of nephrology, in research, in teaching, in quality improvement or whatever you enjoy; it will mitigate against the 80% of the job that you will find mundane and also improve your job prospects.
It is good for all trainees to gain some experience in research, even if only to be able to understand and appraise some of the advances that will occur over the next 30 years during which you will be practicing medicine. A career in clinical academia is very rewarding but challenging. It’s great to have that ‘Eureka moment’ and be the first person in the world to discover the importance of a particular molecule or pathway. For the lucky few investigators it might just lead to a novel therapy that could improve the quality of life for a much larger number of people than you could influence in clinical medicine alone. The downside of a career in academia is that you are only as good as your last grant and you have to be mentally tough to accept that unless you’re very lucky or gifted most of your grant applications will be unsuccessful. You also need to deal with a certain degree of job insecurity both for yourself and your research team.
10. What are your plans for the future?
I have thoroughly enjoyed my time in research thus far and I am keen to pursue a career in clinical academia. I am currently coming towards the end of my Clinician Scientist Fellowship and I am developing models and collaborations that will lead towards a Senior Fellowship application. Ideally in 5-10 years time I will be an established clinical academic with a burgeoning research group and identifying novel pathways that may some day lead to novel therapies for some of the difficult clinical issues listed above.