Current Venture Grants

2021-2022

David Harriman – Urine Microbiome Profiling in Kidney Transplant Recipients in Health and Disease

Kidney transplant represents the best treatment for those with end stage renal disease, however transplant recipients have weakened immune systems secondary to anti-rejection medications that are necessary to prevent organ rejection with subsequent failure. Recently, specific bacterial communities have been found to reside in the urinary tract which may influence the immune system, the so-called urinary microbiome. The urinary microbiome has not been extensively investigated in kidney transplant patients. The goal of this project is to understand the role urinary bacteria play in renal transplant patients and their associated influence on the transplanted kidney and the immune system. This work will explore if urinary bacteria directly influence the transplanted kidney, potentially maintaining or exacerbating the health of that kidney. Adult and pediatric renal transplant recipient urine, with associated clinical information, will be examined to determine bacterial compositions that live in the urine in both healthy post-transplant states and during kidney transplant rejection using state of the art laboratory techniques (16S rRNA sequencing).

Furthermore, the urine bacterial environments of male and female patient will be examined as there have been reported differences in the urinary microbiome based on gender related to hormonal and anatomic considerations in non-transplant patients. If successful, this study will pave the way for future projects aimed at developing tools to identify and halt kidney transplant injury so that transplant recipients can maintain their health for as long as possible.

Caigan Du – Evaluation of propyl gallate for limitation of cold ischemic injury in organ preservation

Organ transplantation starts from a surgical procedure – removing an organ from a donor body and then implanting it into a recipient. However, cells of the donor organ die immediately after the blood supply is disrupted; thus, the donor organ must be perfused and stored in a cold preservation solution to control its damage. There are several preservation solutions available, but none of them performs ideally, particularly in the preservation of the deceased donors because a large number (up to 50%) of them don’t not work properly after transplantation. As a result, it increases the health care cost of transplant patients, shortens implanted organ survival and limits use of those deceased donors. This project seeks to develop a better cold preservation solution based on a novel hyperbranched polyglycerol and propyl gallate. Preliminary studies show that the HPG-based preservation solution protects the organs to be transplanted superior to any of the current methods available. Addition of propyl gallate to this HPG solution or standard University of Wisconsin (UW) solution further prevents cell death in three different human cells. In this proposal, a preclinical model will be used to confirm the increased prevention of donor kidney injury by addition of propyl gallate to the organ preservation solution. It is anticipated that the success of this project will have significant impact: on patient’s recovery after surgery; increasing the donor pool to benefit more Canadians who need a transplant to save their life; and will translate to significant savings to Canadian health care system.