The Kidney Foundation of Canada

Dr. Alp Sener

Dr. Alp Sener

Lawson Health Research Institute, ON

Evaluating the protective role of a novel mitochondria-targeted hydrogen sulphide donor molecule against ischemia reperfusion injury in an ex vivo model of human donation after cardiac death renal transplantation

Co-applicant(s): Ayub Akbari

2018-2020:  $100,000 |  Biomedical Research Grants  |  Category: Transplantation

Lay Summary

Kidney failure is on the rise, with 1 out of every 1000 Canadians currently on dialysis. Sadly, this number continues to increase by 5% each year. Half of these dialysis patients will die from complications of kidney failure within 5 years. Although kidney transplantation is the best manner in which to treat kidney failure, only a limited number of donor organs are available. To overcome this, centers have begun to transplant kidneys from donors after cardiac death (DCD). This involves the use of organs from donors whose hearts have stopped beating prior to donation. Unfortunately, these kidneys are very prone to injury that occurs as a result of the decreased blood flow and oxygen they experience during the dying process. This damage leads to increased organ rejection, and poor transplant kidney function in patients.

We have previously shown, in animal models of kidney transplantation, that the supplementation of organ preservation solutions with NaHS, a hydrogen sulphide (H2S) donor and a naturally occurring compound in all animals, leads to an impressive improvement in kidney function and recipient survival. With this grant, we propose to evaluate and understand the protective role of H2S using a novel H2S donor molecule (AP39) which targets the mitochondria, the powerhouse of the cell, in DCD models which we have developed in the lab using discarded human kidneys. Our findings will not only enable future human clinical trials but also play a role in improving existing organ preservation techniques. Ultimately, the proposed work has the potential to positively alter the outcomes of patients receiving kidney transplants.
 

Biography

Dr. Alp Sener earned his Biology degree from the University of Texas at Austin in 1994. Upon concluding his undergraduate studies, he obtained his PhD in renal physiology in 1999, followed by his MD in 2002 from the University of Calgary. Subsequently, Dr. Sener completed his Urology residency at Western University and became a fellow of the Royal College of Physicians and Surgeons of Canada in 2007. Dr. Sener spent two years at the University of Maryland Medical Center in Baltimore as the American Society of Transplant Surgeons/Novartis Fellow in Transplantation. While in Maryland, he was trained in kidney and pancreas transplantation and completed a research fellowship in transplant immunology. Dr. Sener joined the Division of Urology in 2009 as an Assistant Professor of Surgery and of Microbiology & Immunology, and was the first surgeon to receive the Schulich Clinician Scientist award from the Western University.

Dr. Sener has been the recipient of local, national and international research contribution awards, including the Western University Dean’s Award of Excellence, the Canadian Society of Transplantation Research Excellence Award and the Vanguard Award from the American Society of Transplant Surgeons. He has published 86 peer-reviewed articles and 139 conference abstracts. He is the Founder and Chair of the Canadian Association of Chairs of Surgical Research. Dr. Sener also serves as the Chair of the Surgical Research Committee for the Department of Surgery and is the Director of the Kidney/Pancreas Transplant Fellowship program and of the Urology Residency Program at Western University.

In addition to a general urology and kidney/pancreas transplant-directed clinical practice, Dr. Sener maintains an active basic sciences and translational research laboratory focusing on the innate and adaptive immune responses in graft rejection as well as in developing novel methods of mitigating organ injury associated with transplantation. His laboratory has pioneered the use of hydrogen sulphide in mitigating organ injury associated with transplantation, in modulating neovascularization and metastasis of renal cell carcinoma cell lines and in mitigating tissue fibrosis following chronic urinary obstruction. He is heavily involved in promoting research and education through his national and international active roles in both Urology, (American Urological Association Research Advocacy Committee, AUA Northeastern Section Board of Directors; Canadian Urological Association Research and Education Committees and as President of the Urological Society of Transplant and Renal Surgeons), and Transplant organizations (Canadian Society of Transplantation Research Committee and American Society of Transplant Surgeons Vanguard Committee).