I received both MD and PhD from McMaster University. My clinical practice involves general nephrology, chronic kidney disease, and dialysis with a special interest in peritoneal dialysis.
Research
- I have published extensively on adenovirus mediated gene transfer to the peritoneum and used this as a model to understand basic mechanisms of fibrosis. Peritoneal epithelial cells undergo a transition and become fibroblast like cells which contributes to peritoneal fibrosis. We have used the peritoneal tissue as a model of this process and begun to understand the mechanisms involved (JASN 2005, KI 2010, Matrix Biology 2010). We are also interested in the interaction between fibrosis and angiogenesis and have used known pharmaceutical agents to block the hypoxic response which we believe is partly driving this angiogenesis.
- We are interested in the role of the fibrogenic molecule transforming growth factor β and its effect on the cells within the filters of the kidney. We have also looked at the effect of damaging the filters (glomeruli) of the kidney, and the role this plays in altering the blood vessels downstream which are essential for proper tubular function.
- I also collaborate with colleagues in human clinical and translational studies including evaluation of novel methods of volume assessment and the interaction between markers of inflammation, volume expansion, cardiovascular disease, and clinical outcomes.
Funding
In 2010, I am funded through a CIHR operating grant ($100,000), salary support ($50,000), and industry funding ($60,000). In the past 3 years, I have had approximately $750K in funding (CIHR operating +salary $400K, Kidney Foundation $50K, industry funding $275K, CFI 25K).
Personnel
I presently have full time technician and a PhD student in the lab. In May 2010, 2 MSc students graduated. I also supervise a clinical fellow doing research on fibrocytes in human renal disease. I have a post-doctoral fellow starting in August 2010.
Future work
Aside from pursuing areas outlined above, we are very excited about two potential projects.
- We are developing novel gene therapy vectors for therapeutic use in progressive kidney disease. We have taken a 3 rd generation or ‘gutless’ adenovirus vector and modified the capsid proteins to get better adhesion to the renal vasculature and therefore greater expression in the kidney. We are collaborating with Dr. Mick Bhatia in developing HDAd vectors that express factors that may induce dedifferentiation of cells in an injured tissue or organ. This work is very preliminary, but we believe we can develop therapeutic approaches for potential tissue regeneration.
- We are collaborating with an international group to investigate the genetic susceptibility of progressive fibrosis. Our interest is a rare complication of peritoneal dialysis were patients develop progressive, massive scarring of the peritoneal cavity which is usually life-threatening. We are exploiting a mouse strain difference in response to fibrogenic stimuli to initiate the search for genetic susceptibility, and will then screen identified genes in patients with encapsulating peritoneal sclerosis.
Recruitment and retention
My research would benefit greatly by the recruitment of junior faculty with an interest in gene therapy and kidney disease. An interest in stem cell biology or renal development would also be an asset. This recruit would require approximately $80K/year in salary along with start up funding ($150K). This recruit would work on aspects of the first project outlined above. Funding for a post-doctoral fellow interested in peritoneal membrane research ($45K/year) would also be of considerable value. This individual would work on the second project outlined above.
Publications
Via PubMed, http://www.ncbi.nlm.nih.gov/pubmed?term=Margetts%20PJ