Integrative high-resolution multi-omics and targeted approaches in patients with IgAN

Background

IgA Nephropathy (IgAN) is an immune-mediated disease characterized by accumulation of immunoglobulin A in the kidney, where it mounts an inflammatory response that damages the kidney.

One key problem is that the human IgA is unique such that no animal models exist that allow to study early disease mechanisms of the human disease. Human studies are therefore key to dissect mechanistically how these components contribute to the pathophysiology of IgAN.

We propose a multi-omics characterization of kidney biopsies and blood of human patients from a carefully selected cohort of IgAN patients and controls from patients of other kidney conditions as well as healthy individuals. We will combine bulk and single-cell transcriptomics from biopsies and blood, peptidomics from blood and tissue proteomics via imaging mass spectrometry from biopsies. These –omics approaches will augment existing genetic, transcriptomics and peptidomic datasets. The data will be integrated using a combination of state-of-the-art computational approaches.

The outcomes of this project will hopefully shed new light on the mechanisms underlying IgAN paving the way for developing novel biomarkers and therapies.

Key literature

  1. Tajti F, et al. A Functional Landscape of CKD Entities From Public Transcriptomic Data. Kidney Int Rep (2020).
  2. Türei D, Korcsmáros T, Saez-Rodriguez J. OmniPath: guidelines and gateway for literature-curated signaling pathway resources. Nat Methods (2016).
  3. Rauen T, et al. After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy. Kidney Int (2020).
  4. Rauen T, et al. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med (2015).