Project P8
Dissecting IgA nephropathy via integration of multi-omics data
Associated Advisor as Senior Professor, Medical Clinik I and II, University hospital RWTH Aachen Dr. med. Claudia Seikrit
Department and Chair of Internal Medicine (with a focus on Nephrology and Immunology)
University hospital RWTH Aachen
E-Mail: cseikrit@ukaachen.de
Department and Chair of Internal Medicine (with a focus on Nephrology and Immunology)
Univ.-Prof. Dr. Ing. Julio Saez-Rodriguez
Institute for Computational Biomedicine
Heidelberg University, Faculty of Medicine
E-Mail: pub.saez@uni-heidelberg.de
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.
Tajti F, Kuppe C, Antoranz A, Ibrahim MM, Kim H, Ceccarelli F, Holland CH, Olauson H, Floege J, Alexopoulos LG, Kramann R#, Saez-Rodriguez J#. A Functional Landscape of CKD Entities From Public Transcriptomic Data. Kidney Int. Reports 2019, 5(2):211-224
Türei D, Korcsmáros T, Saez-Rodriguez J. Omnipath: guidelines and gateway for literature-curated signaling pathway resources. Nature Methods 2016, 13:966, 2016 → Cover Nature Methods
Rauen T, Wied S, Fitzner C, Eitner F, Sommerer C, Zeier M, Otte B, Panzer U, Budde K, Benck U, Mertens PR, Kuhlmann U, Witzke O, Gross O, Vielhauer V, Mann JFE, Hilgers RD, Floege J. After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy. Kidney Int. 2020, doi: 10.1016/j.kint.2020.04.046
Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR, Kuhlmann U, Witzke O, Gross O, Vielhauer V, Mann JF, Hilgers RD, Floege J. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med. 2015. 373:2225-36
Selected Publications