Research Group

  • Dr. Anette Melk, Principal Investigator


  • University of Heidelberg, Heidelberg, Germany


  • Cell Cycle Regulator p16 as a Mechanism for Long-Term Graft Failure

The survival of transplanted kidneys is shorter than the expected survival in the organ donor. This is due to many stresses that occur during the transplantation process (e.g. duration of ischemia, rejection episodes). The histological picture of such a damaged organ resembles the features of a normally-aged old kidney. This disease of the transplanted kidney is called allograft nephropathy (AN). Because of the similarities of AN to aging, we hypothesized that AN could be a state of accelerated aging of the kidney.

In our previous work, we found that p16, a protein regulating cell replication, is strongly associated with kidney aging and is also induced in transplanted, rejected kidneys. The aim of this project is to prove that p16 is a key player in the development of AN. To do this we will use mice deficient in the functional p16 gene (p16 KO) in a transplantation model. The outcome will be compared with wild-type mice (wt) that carry a functional p16 gene. We expect that p16 KO mice will show less severe histological changes and better graft function than wt mice. The material from these mice will be used to explore the p16 regulation in detail by using specific methods for detection of gene and protein expression in the whole kidney and in different cell types within the kidney. This part of the project will provide new insights in the so far poorly understood regulation of p16 expression in vivo. Finally, we will transfer the animal data to the human situation by investigating p16 in human renal biopsies from transplanted kidneys. We will examine whether p16 is a predictor of graft survival. Thus, p16 could emerge as an important marker to estimate the real potential of transplanted kidneys. This is particularly important as the actual organ shortage forces the use of older and diseased kidneys.