Collaborative Research Center 1453

NephroGenetics

Kidney disease represents a global public health challenge. Chronic kidney disease alone affects 10-15% of adults, and kidney cancers add to this burden. Despite the high prevalence and the great costs associated with treating kidney diseases, the low number of clinical trials and specific treatments in nephrology attests to a shortage of therapeutic targets. The identification of druggable targets has been complicated by an incomplete understanding of the underlying mechanisms. Pharmacological compounds that operate on proteins or pathways connected to a given disease by human genetic evidence are twice as likely to successfully move through the clinical development pipeline, compared to those with no genetic support. Therefore, NephGen will use evidence from both monogenic and complex genetic kidney diseases to identify and characterize molecules and pathways that represent targets to improve the prevention and treatment of kidney disease. To this end, NephGen researchers have assembled large patient- and population-studies, and established a variety of model organisms and state-of-the-art methods for genome editing, (single-cell) sequencing, structural biology, diverse omics technologies, whole animal live imaging as well as integrative analyses and modeling of high-dimensional data. To facilitate clinical translation, NephGen will use both modern statistical approaches and modify the implicated molecules and pathways in disease-specific model organisms through genetic and pharmacological approaches.

Research Program

Publications

Dizin E, Olivier V, Roth I, …, Frew I, Feraille E.  Activation of the Hypoxia-Inducible Factor Pathway Inhibits Epithelial Sodium Channel-Mediated Sodium Transport in Collecting Duct Principal Cells. JASN (2021). Getwan M, Hoppmann A, Schlosser P, …, Lausch E, Köttgen A, Lienkamp SS. Ttc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polycystic kidney disease. Proc. Natl. Acad. Sci. USA 118:39 (2021). Antony D, Brunner HG, Schmidts M. Ciliary Dyneins and Dynein Related Ciliopathies. Cells, 10:1885 (2021). Knoers N, Antignac C, Bergmann C, Dahan K, Giglio S, …, Schaefer F, ERA-EDTA Working Group for Inherited Kidney Diseases (WGIKD), the Molecular Diagnostics Taskforce of the European Rare Kidney Disease Reference Network (ERKNet). Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice. Nephrology Dialysis Transplantation (2021). Schüle I, Berger U, Matysiak U, Ruzaike G, Stiller B, …, Lausch E, Grünert SC, Schmidts M. A Homozygous Deletion of Exon 5 of KYNU Resulting from a Maternal Chromosome 2 Isodisomy (UPD2) Causes Catel-Manzke-Syndrome/VCRL Syndrome. Genes, 12:879 (2021). Sanderson LE, Lanko K, Alsagob M, Almass R, Al-Ahmadi N, …, Schmidts M, Barakat TS, van Ham TJ, Kaya N. Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking. Brain, 144:769-780 (2021). Grünert S, Matysiak U, Hodde F, Ruzaike G, Lausch E, Schumann A, van der Werf-Grohmann N, Spiekerkötter U, Schmidts M. Isolated Hypomethylation of IGF2 Associated with Severe Hypoglycemia Responsive to Growth Hormone Treatment. Diagnostics, 11:749 (2021). More Publications