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

Steinbrenner I, Köttgen A. A polygenic score predicts CKD across ancestries. Nat Rev Nephrol (2022). Olinger E, Schaeffer C, Kidd K, Elhassan EAE, Cheng Y, …, Köttgen A, …, Sayer JA, Rampoldi L, Devuyst O. An intermediate-effect size variant in UMOD confers risk for chronic kidney disease. Proc Natl Acad Sci USA (2022). Jiao H, Wachsmuth L, Wolf S, Lohmann J, Nagata M, …, Schell Ch, Young GR, Kassiotis G, Pasparakis M. ADAR1 averts fatal type I interferon induction by ZBP1. Nature (2022). Gorski M, Rasheed H, Teumer A, Thomas LF, Graham SE, .., Köttgen M, …, Köttgen A, Kronenberg F, Heid IM. Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies. Kidney Int (2022). Hölzen L, Mitschke J, Schönichen C, Hess ME, Ehrenfeld S, Boerries M, Miething C, Brummer T, Reinheckel T. RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells. Theranostics (2022). Mahajan A, Spracklen CN, Zhang W, Ng MCY, Petty LE, …, Wuttke M, …, Köttgen A, …, Rotter JI, McCarthy MI, Morris AP. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nat Genet (2022). Steinbrenner I, Sekula P, Kotsis F, von Cube M, Cheng Y, …, Eckardt KU, Schultheiss UT, GCKD investigators. Association of osteopontin with kidney function and kidney failure in chronic kidney disease patients: the GCKD study. Nephrol Dial Transplant (2022). Yasunaga T, Wiegel J, Bergen MD, Helmstädter M, Epting D,…, Walentek P, Ulbrich MH, Walz G. Microridge-like structures anchor motile cilia. Nat Commun (2022). Devane J, Ott E, Olinger EG, Epting D, Decker E, …, Boerries M, Metzger P, Schell C, …, Schlevogt B, Sayer JA, Bergmann C. Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations. Am J Hum Genet (2022). More Publications