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Prof. Dr. Peter Nürnberg

Principal Investigator, Cologne Center for Genomics (CCG)

Prof. Dr. Peter Nürnberg
Principal Investigator, Cologne Center for Genomics (CCG)
Tel.  +49 221 478 96801
nuernberg[at]uni-koeln.de

Cologne Center for Genomics
Uniklinik Köln
Weyertal 115b
50931 Köln
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Peter Nürnberg

Dupuytren’s contracture (DC) is one of the most common genetic disorders of connective tissue. Prof. Dr. Peter Nürnberg and his team are looking at the pathogenetic mechanisms that lead to the development of this condition. Genome-wide association studies have enabled them to identify variants in nine different gene loci that are associated with the occurrence of the disease.

Our research: Dupuytren’s contracture is a multifactorial disease whose causes include genetic variation, cell stress, and inflammatory activity. Prof. Nürnberg’s research group is focusing on identifying the many genetic variants that are associated with DC.

Our successes: In a genome-wide association study (GWAS), the team has been able to identify nine significant gene loci that are associated with the onset of DC. Six of these regions contain genes that code for Wnt signaling components. These findings may provide evidence concerning the pathological mechanisms responsible for Dupuytren’s contracture.

Our goals: The research group has developed methods to determine the contractility of myofibroblasts under various conditions. In this way, age-associated and stress-induced changes can be characterized and distinguished to give a better understanding of the pathology of DC and other fibrotic diseases.

Our methods/techniques: The research group has developed methods of determining the contractility of myofibroblasts under various conditions. In this way, age-associated and stress-induced changes can be characterized and distinguished to give a better understanding of the pathology of DC and other abnormal fibroblast differentiation.

Figures
Figure 1
Figure 2

Figure 1: Contraction of fibroblast populated 3-dimensional collagen gels monitored over 10 days. Gel contraction for one patient and one control (normal human fibroblasts) is shown. Patient cells rapidly contract the collagen gel visibly already at day two. The former attached gel detaches itself from the well wall within 24 hours. Control gels detach only after several days, while gels without cells (neg. control) do not contract.

Figure 2: Manhattan plot of the GWAS meta-analysis for Dupuytren’s disease (N = 5803). The plot shows -log10-transformed P-values for all SNPs (N = 4,350,741). SNPs depicted in green surpass the genome-wide significance level of P<5x10-08.

EXTERNAL Cooperations
  • Prof. Dr. R. Fodde, Erasmus University Medical Center Rotterdam, NL
  • Prof. Dr. B. Hinz, Laboratory of Tissue Repair and Regeneration, University of Toronto, CA
  • Prof. Dr. A. Jackson, Institute of Genetics and Molecular Medicine, University of Edinburgh, UK
  • Dr. S. Sakakibara, Faculty of Human Sciences, Waseda University, Tokorozawa, JP
  • Prof. Dr. med. S. Tinschert, Medizinische Universität Innsbruck, AT
  • Prof. Dr. C. Wijmenga, Dept Genetics (MGE), UMCG, Groningen, NL