Polimorph

Polimorph


Polimorph stands for the project "Prolongation of kidney transplant survival through risk stratification of omics-wide incompatibilities using systems biology - a personalized medicine approach"



Description


Chronic rejection of renal allografts is driven by antibody-mediated rejection (ABMR). Epidemiological data suggest, that besides HLA mismatches alloantibodies directed against minor histocompatibility antigens (mHA) play an important role, but clinical relevance remains unresolved. An unexpected diversity in the human genome has been identified, most importantly based on non-synonymous single nucleotide polymorphisms (nsSNP) and loss of function variants (LoF), representing a plausible source for alloreactivity in mismatched donor and recipient (D/R) pairs. Genome-wide genetic incompatibilities (GWGI) in D/R pairs have not been studied systematically. In this project we propose a systems biology approach integrating omics data to address this question. We have established a large prospective transplant biobank now including over 2000 transplant recipients. D/R pairs will be genotyped and using our bioinformatics pipeline nsSNP and LoF mismatches will be identified. We will then identify linear epitopes in these mismatched proteins to be integrated on customized high-density peptide arrays to screen for alloantibodies. Finally, we will establish a predictive model for graft function and survival based on the individual GWGI in D/R pairs integrating our proteomics and genomics data as well as established risk stratifiers. This will ultimately allow for a better matching of D/R pairs and guide personalized immunosuppressive strategies based on the individual risk for rejection.

Polimorph is an interdisciplinary multi-year research project funded by the Vienna Science and Technology Fund (WWTF - LS16-019). It has started in January 2017 and will run until 2019. The project is directed by Rainer Oberbauer at the Medical University of Vienna.


About WWTF.


News


Meet us at the Kidney Week of the ASN in New Orleans, LA

The Polimorph project will present a poster at the Kidney Week (Session Date: November 2, 2017 from 10:00 AM to 12:00 PM) on the Poster Board #: TH-PO998). See you there!

16th of March, 2017: Kick-Off Meeting

Our Project Kick-Off Meeting took place on the 16th of March, 2017 in the Jugendstilhörsaal, Medical University, Vienna. The purpose of the meeting was firstly to introduce the Polimorph project together with our partners to the guests.
After the welcoming words from Rainer Oberbauer (Project Coordinator) and Markus Müller (Rector of Medical University), Michaela Fritz (Vice-Rector for Research and Innovation) and Michael Stampfer (Managing Director of WWTF) talked about the strategic alliance between the partners and about the mission of WWTF, respectively.
We had also the great opportunity to hear a lecture about the use of big data in personalized transplantation from Dorry Segev, Johns Hopkins School of Medicine. Last but not least, three of the main investigators from Polimorph (Nikolina Papac-Milicevic, Stephan Pabinger and Roman Reindl-Schwaighofer) explained in a moderated discussion the background, the purpose and the workpackages of Polimoprh.


Nikolina Papac-Milicevic, Stephan Pabinger, Roman Reindl-Schwaighofer and Rainer Oberbauer


Meet the team


Rainer

Rainer Oberbauer

Project Coordinator

Medical University of Vienna




homepage

Stephan

Stephan Pabinger

Project Partner

Austrian Institute of Technology




homepage

Christoph

Christoph Binder

Project Partner

Research Center for Molecular Medicine



homepage

Rainer Oberbauer is the coordinator of the Polimorph project. He contributes with his expertise to the experimental-computational, as well as to the medical approaches, organizing the sample and data collection for the biobank and analyzing medical benefits. He designed and established the genomics and proteomics workflow to analyze the D/R pairs. Dr. Oberbauer ́s laboratory is embedded in the Syskid network and the Beat DKD, both brings together research institutions in the field of systems biology and omics technology focusing on novel diagnostic approaches and treatment strategies in kidney disease, as well as in the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN consortium), that aims to uncover the genetic underpinnings of graft rejection [9, 10]. The network was formed in late 2012 to bring together a number of academic research organizations across Europe, America and beyond. The Oberbauer group has joined the Consortium in 2014 and it is co-leading the iGeneTRAiN LoF efforts. The iGeneTRAiN's main aims are two-fold: a) assessment of the fundamental genetic underpinnings of rejection (in HLA and non-HLA loci) and b) improvement of graft outcome through the identification of new biomarkers for early detection of rejection and better matching of D/R pairs.
You can learn more from the iGeneTRAiN video, or check out their website.

iGeneTRAiN UK from iGeneTRAiN on Vimeo.



Stephan Pabinger is part of national and international research consortia dealing with genomics and bioinformatics for the elucidation of disease mechanisms and diagnostic possibilities. He has extensive experience in genome-wide analysis and integration of genomic, epigenomic and transcriptomic data in the context of biomarker discovery and validation. Within this project he will set up data analysis pipelines which aim to integrate genomic and proteomic data of D/R pairs with clinical data in long-term graft survival after kidney transplantation.

Christoph Binder is an expert on humoral immunity and atherosclerosis. His laboratory is interested in the role of natural IgM antibodies and regulators of complement in tissue homeostasis with respect to chronic inflammation. Within this project, levels of natural IgM antibodies and the binding properties of regulators of complement activation (RCA),will be assessed in recipient sera to evaluate their influence on ABMR. Moreover, genotyping data of individuals will be used to identify genetic determinants that influence both levels and binding properties of natural IgM and RCA members and how these modulate graft survival.


Publications


1. Strategies for long-term preservation of kidney graft function.
Wekerle T, Segev D, Lechler R, Oberbauer R.
Lancet 2017 May 27;389(10084):2152-2162.

2. Mechanisms underlying human genetic diversity: consequence for anti-graft antibody responses.
Reindl-Schwaighofer R, Heinzel A, Signorini L, Thaunat O, and Oberbauer R.
Transplant Int, 2018 Mar; 31(3):239-250.

3. Regresion of left atrial diameter after kidney transplantation is associsated with prolonged survival: an observational study.
Regele F, Kainz A, Kammer M, Beer A, Steringer-Mascherbauer R, Binder T, and Oberbauer R.
accepted in Transplant Int, 2018

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