Rainer Oberbauer  Christoph Binder
Principal Investigator:
Rainer Oberbauer Personal webpage
Institution:
Medical University of Vienna Webpage
Projekttitel:
Prolongation of kidney transplant survival through risk stratification of omics-wide incompatibilities using systems biology - a personalized medicine approach
ProjektpartnerInnen:
Christoph Binder (CeMM - Research Center for Molecular Medicine GmbH of the Austrian Academy of Sciences) (Co-Principal Investigator) Personal webpage
Weitere ProjektpartnerInnen:
Stephan Pabinger (Austrian Institute of Technology GmbH)
Status:
Laufend (01.01.2017 – 31.12.2019) 36 Monate
Fördersumme:
€ 879.500

 
Kurzzusammenfassung:

50% of kidney transplants are lost within ten years. This is mainly driven by chronic antibody-mediated rejection (ABMR). Epidemiological data suggests a significant contribution of antibodies directed against mismatches in non-HLA epitopes, but clinical significance remains unclear. The diversity of the human genome is reflected by 10-20 homozygous loss of function (LoF) variants and several thousand non-synonymous single nucleotide polymorphisms (nsSNP) per individual. We hypothesize that such genome-wide genetic incompatibilities in donor / recipient (D/R) result in chronic ABMR and graft dysfunction. We have established a large and well phenotyped biobank including genotype data from > 800 D/R pairs using a genome-wide transplant specific gene arrays that will be imputed to cover > 80 million variants. For an assessment of the humoral alloimmunity we will combine a whole proteome protein array with a customizable high-density peptide array. ABMR is mainly driven by complement mediated injury. Complement itself is highly polymorphic. We will therefor evaluate recipient-specific activities of complement regulators on a genetic and functional level to assess complement activation and regulation in response to alloimmune stimulation. Using a systems biology approach to integrate this novel multi-omics data set into a predictive model of transplant outcome, we will be able to better match D/R kidney transplant candidates. Improved matching will most likely lead to less alloimmune response and thus longer graft and patient survival. Keywords: kidney transplantation, chronic antibody-mediated rejection, non-HLA, genome-wide genetic incompatibility, nsSNP, loss of function proteins, complement activity

 
Scientific disciplines: 106014 - Genomics (40%) | 102004 - Bioinformatics (30%) | 106044 - Systems biology (30%)

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