Project P2
Dissecting regulatory programs of kidney disease transition using functional genomics
PD Dr. med. Christoph Kuppe
Institute of Experimental Medicine and Systems Biology
Department of Internal Medicine II, Nephrology
University hospital RWTH Aachen
E-Mail: ckuppe@ukaachen.de
Univ.-Prof. Dr. rer. nat. Ivan G. Costa
Institute for Computational Genomics
Joint Research Center for Computational Biomedicine
RWTH Aachen University
E-Mail: ivan.costa@rwth-aachen.de
Institute for Computational Genomics
The kidney is one of the most heterogeneous organs with over 50 cell types. We hypothesize that distinct cell specific programs (regulated by transcription factors) govern the transition of glomerular diseases and acute kidney injury (AKI) to chronic kidney disease (CKD) and the response to therapeutics. We will use single-cell sequencing technologies to dissect transcriptional and regulatory programs at an unprecedented throughput and depth targeting tens of thousands of kidney cells. These complementary techniques will allow us to analyze transcriptional and epigenetic changes and provide a finer characterization of cellular state transitions in disease. In conclusion, we aim to use state-of-the-art functional genomics approaches to unravel the complex cellular and molecular heterogeneity of disease transition in experimental mouse models and human kidney diseases (Alport disease and focal segmental glomerulosclerosis, FSGS). Our data will characterize affected cell-specific regulatory pathways and might lead to identification of novel diagnostic and therapeutic approaches.
Kuppe C*, Ibrahim M.M.*, Kranz J*, Zhang X, Ziegler S, Perales-Patón J, Jansen J, Reimer KC, Smith JR, Dobie R, Wilson-Kanamori JR, Halder M, Xu Y, Kabgani N, Kaesler N, Klaus M, Gernhold L, Puelles VG, Huber TB, Boor , Menzel S, Hoogenboezem RM, Bindels EMJ, Steffens J, Floege J, K. Schneider R, Saez-Rodriguez J, Henderson NC, Kramann R. Decoding myofibroblast origins in human kidney fibrosis. Nature 2021 589, 281–286
Li Z*, Kuppe C*, Ziegler S, Mingbo C, Kabgani N, Menzel S, Zenke M, Kramann R, Costa IG. Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen. Nat Commun 12 2021, 6386
Li Z, Schulz MH, Look T, Look T, Begerman, M, Zenke M, Costa IG. Identification of Transcription Factor Binding Sites using ATAC-seq. Genome Biology 2019, 20:45 doi:10.1186/s13059-019-1642-2.
Kuppe C, Leuchtle K, Wagner A, Kabgani N, Saritas T, Puelles VG, Smeets B, Hakroush S, van der Vlag J, Boor P, Schiffer M, Gröne HJ, Fogo A, Floege J, Moeller MJ. Novel parietal parietal epithelial subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions. Kidney Int. 2019, doi: 10.1016/j.kint.2019.01.037.
Gusmao EG, Alhoff M, Zenke M, Costa IG. Analysis of computational footprinting methods for DNase sequencing experiments. Nature Methods 2016, 13:303–309.
Selected Publications