Dontscho Kerjaschki, Clinical Institute of Pathology, Medical University of Vienna

Additional PIs: Christoph Gebehuber PhD, Christoph Kornauth MD

Research Focus: miRNA

Relevance of your Provisional grouping in KidneyConnect:

We have discovered the first pathogenic miRNA in podocytes. Its induced upregulation in adult mice causes reproducibly classical FSGS. We have shown that this miRNA regulates primarily the WT1 transcription factor and we demonstrated that this causes massive down-regulation of gene expression of Neph1 and Podxl that have binding sites for this miRNA. This step is followed by a generalized collapse of scores of components that are essential for maintainance of podocyte shape and function. The development of FSGS in these miRNAoverexpressing mice can be drastically reduced by a specific LNA. Finally, this miRNA is overexpressed in podocytes in about 60% of human FSGS, but in no other renal disease.

We plan to identify additional targets of the miRNA in podocytes, and to find factors that induce the miRNA in vitro and in vivo. This could provide the basis for a rationale specifically targetted treatment of the subset of human FSGS that is not caused by hereditary gene defects or circulating factors (that do not overexpress the miRNA)

Resources Available relevant to your grouping:

  • Special Techniques: All morphologigal techniques
  • Animal Models/Knock Outs: inducible miR-193a transgenic mouse
  • Datasets: RNASeq data of isolated mouse glomeruli
  • Others

Clinical/Translational Resources:

  • Biobanks: large archive of human biopsies
  • Population/Patient Cohorts
  • Special Techniques for Clinical Assessment
  • Patient Groups for Clinical trials
  • Others