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). 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). 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). Aypek H, Krisp C, Lu S, Liu S, Kylies D, …, Bergmann C, Huber TB, Grahammer F. Loss of the collagen IV modifier prolyl 3-hydroxylase 2 causes thin basement membrane nephropathy. J Clin Invest (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). Ziegler WH, Lüdiger S, Hassan F, Georgiadis ME, Swolana K, …, Bergmann C, Soetje B, Haffner D. Primary URECs: a source to better understand the pathology of renal tubular epithelia in pediatric hereditary cystic kidney diseases. Orphanet J Rare Dis (2022). Rogg M, Maier JI, Van Wymersch C, Helmstädter M, Sammarco A, …, Walz G, .., Benzing T, Huber T, Schell C. α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier. J Am Soc Nephrol (2022). Rad A, Najafi M, Suri F, Abedini S, Loum S, …, Hashemi N, Vona B, Schmidts M. Identification of three novel homozygous variants in COL9A3 causing autosomal recessive Stickler syndrome. Orphanet J Rare Dis (2022). Scholl UI. Genetics of Primary Aldosteronism. Hypertension (2022). Epting D, Decker E, Ott E, Eisenberger T, Bader I, Bachmann N, Bergmann C.  The ciliary transition zone protein TMEM218 synergistically interacts with the NPHP module and its reduced dosage leads to a wide range of syndromic ciliopathies. Hum Mol Genet (2022). Sharma R, Sahoo SS, Honda M, Granger SL, Goodings C, …, Boerries M, …, Erlacher M, Coulon S, Wlodarski MW. Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue. Blood (2022). More Publications