Center for Molecular Medicine Cologne

Beck, Bodo | Altmüller, Janine | Erger, Florian - assoc. RG 03

Rare renal disorders identify core aspects of renal homeostasis - an integral approach to discover fundamental molecular principles of the kidney

Introduction

The principle function of the kidney is based on control of renal perfusion and filtration, counter current concentration of solutes, and epithelial transport function. The kidney is one of our major homeostatic organs and controls volume and osmolytes- a prerequisite for maintaining blood pressure as well as specific ion concentration gradients required for the proper function of any cell. The kidney exerts endocrine functions and clears metabolic end products. There are more than 500 rare kidney diseases (including metabolic diseases). Not surprisingly the kidney is affected in metabolic diseases and kidney disease itself is a main cause of metabolic disturbance.
Together with our collaborators from pediatric and adult nephrology our group explores the underlying basis of rare kidney disease by comprehensive genomic profiling.

Figure 1

Our focus

Currently we focus on the following groups of disease, but our brains are always open for new questions and collaborations:

  • already prenatally manifesting kidney disease
  • monogenic forms of nephrolithiasis
  • the genetic basis of proteinuric (SRNS, FSGS, recurrent FSGS) kidney disease and renal thrombotic microangiopathies (rTMA)/atypical haemolytic uremic syndrome (aHUS),
  • the spectrum of autosomal dominant tubulointertstitial kidney disease (ADTKD)
  • establishing kidney derived cell free DNA as a biomarker for renal disease,
  • implementation of new sequencing and bioinformatic approaches to uncover renal disease.

Using complementary methods for comprehensive genomic profiling in rare kidney disease allows us to discover missing aspect and system links required for a more accurate understanding  of renal homeostasis. Integration of the data will open novel therapeutic avenues for RKD’s that may also prove pivotal for treatment of common disorders.

  • Bartram MP, Habbig S, Pahmeyer C, Höhne M, Weber LT, Thiele H, Altmüller J, Kottoor N, Wenzel A, Krueger M, Schermer B, Benzing T, Rinschen MM, Beck BB. Three-layered proteomic characterization of a novel ACTN4 mutation unravels its pathogenic potential in FSGS. Hum Mol Genet. 2016;25(6):1152-64. PubMed PMID: 26740551
  • Laghmani K, Beck BB, Yang SS, Seaayfan E, Wenzel A,Reusch B, Vitzthum H, Priem D, Demaretz S, Bergmann K, Duin LK, Göbel H, Mache C, Thiele H, Bartram MP, Dombret C, Altmüller J, Nürnberg P, Benzing T, Levtchenko E, Seyberth HW, Klaus G, Yigit G, Lin SH, Timmer A, de Koning TJ, Scherjon SA, Schlingmann KP, Bertrand MJ, Rinschen MM, de Backer O, Konrad M, Kömhoff M. Polyhydramnios, Transient Antenatal Bartter's Syndrome, and MAGED2 Mutations. N Engl J Med. 2016 May 12;374(19):1853-63. doi: 10.1056/NEJMoa1507629. Epub 2016 Apr 27. PubMed PMID: 27120771
  • Beck BB, van Spronsen F, Diepstra A, Berger RM, Kömhoff M. Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity. Pediatr Nephrol. 2017;32(5):733-741 PubMed PMID: 27289364
  • Wenzel A, Altmueller J, Ekici AB, Popp B, Stueber K, Thiele H, Pannes A, Staubach S, Salido E, Nuernberg P, Reinhardt R, Reis A, Rump P, Hanisch FG, Wolf MTF, Wiesener M, Huettel B, Beck BB. Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations. Sci Rep. 2018 Mar 8;8(1):4170. doi: 10.1038/s41598-018-22428-0. PubMed PMID: 29520014
  • Erger F, Nörling D, Borchert D, Leenen E, Habbig S, Wiesener MS, Bartram MP, Wenzel A, Becker C, Toliat MR, Nürnberg P, Beck BB, Altmüller J. cfNOMe - A single assay for comprehensive epigenetic analyses of cell-free DNA. Genome Med. 2020;12(1):54. PubMed PMID: 32580754
  • Burgmaier K, Brinker L, Erger F, Beck BB, Benz MR, Bergmann C, Boyer O, Collard L, Dafinger C, Fila M, Kowalewska C, Lange-Sperandio B, Massella L, Mastrangelo A, Mekahli D, Miklaszewska M, Ortiz-Bruechle N, Patzer L, Prikhodina L, Ranchin B, Ranguelov N, Schild R, Seeman T, Sever L, Sikora P, Szczepanska M, Teixeira A, Thumfart J, Uetz B, Weber LT, Wühl E, Zerres K; ESCAPE Study group; GPN study group, Dötsch J, Schaefer F, Liebau MC; ARegPKD consortium. Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants. Kidney Int. 2021 Apr 30:S0085-2538(21)00459-2
  • Schlingmann KP, Jouret F, Shen K, Nigam A, Arjona FJ, Dafinger C, Houillier P, Jones DP, Kleinerüschkamp F, Oh J, Godefroid N, Eltan M, Güran T, Burtey S, Parotte MC, König J, Braun A, Bos C, Ibars Serra M, Rehmann H, Zwartkruis FJT, Renkema KY, Klingel K, Schulze-Bahr E, Schermer B, Bergmann C, Altmüller J, Thiele H, Beck BB, Dahan K, Sabatini D, Liebau MC, Vargas-Poussou R, Knoers NVAM, Konrad M, de Baaij JHF. mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy. J Am Soc Nephrol. 2021 Nov;32(11):2885-2899. doi: 10.1681/ASN.2021030333. Epub 2021 Oct 4. PMID: 34607910
  • Reusch B, Bartram MP, Dafinger C, Palacio-Escat N, Wenzel A, Fenton RA, Saez-Rodriguez J, Schermer B, Benzing T, Altmuller J, Beck BB, and Rinschen MM (2022). MAGED2 controls vasopressin-induced aquaporin-2 expression in collecting duct cells. J Proteomics252, 104424. doi:10.1016/j.jprot.2021.104424.
  • Wopperer FJ, Knaup KX, Stanzick KJ, Schneider K, Jobst-Schwan T, Ekici AB, Uebe S, Wenzel A, Schliep S, Schurfeld C, Seitz R, Bernhardt W, Godel M, Wiesener A, Popp B, Stark KJ, Grone HJ, Friedrich B, Weiss M, Basic-Jukic N, Schiffer M, Schroppel B, Huettel B, Beck BB, Genomics England Research C, Sayer JA, Ziegler C, Buttner-Herold M, Amann K, Heid IM, Reis A, Pasutto F, and Wiesener MS (2022). Diverse molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases. Kidney Int. doi:10.1016/j.kint.2022.04.031.
  • Conrad T, and Altmuller J (2022). Single cell- and spatial 'Omics revolutionize physiology. Acta Physiol (Oxf), e13848. doi:10.1111/apha.13848.
  • Mandrile G, Beck B, Acquaviva C, Rumsby G, Deesker L, Garrelfs S, Gupta A, Bacchetta J, Groothoff J, and OxalEurope Consortium/Erknet Guideline Workgroup On H (2022). Genetic assessment in primary hyperoxaluria: why it matters. Pediatr Nephrol. doi:10.1007/s00467-022-05613-2.
  • Boeckhaus J, Hoefele J, Riedhammer KM, Nagel M, Beck B, Choi M, Gollasch M, Bergmann C, Sonntag JE, Troesch V, Stock J, and Gross O (2022). Lifelong Effect of Therapy in Young Patients with the COL4A5 Alport Missense Variant p.(Gly624Asp): a Prospective Cohort Study. Nephrol Dial Transplant. doi:10.1093/ndt/gfac006.
  • Leenen E, Erger F, Altmuller J, Wenzel A, Thiele H, Harth A, Tschernoster N, Lokhande S, Joerres A, Becker JU, Ekici A, Huettel B, Beck B, and Weidemann A (2022). Alport syndrome and autosomal dominant tubulointerstitial kidney disease frequently underlie end stage renal disease of unknown origin - a single center analysis. Nephrol Dial Transplant. doi:10.1093/ndt/gfac163.
  • Metry EL, Garrelfs SF, Peters-Sengers H, Hulton SA, Acquaviva C, Bacchetta J, Beck BB, Collard L, Deschenes G, Franssen C, Kemper MJ, Lipkin GW, Mandrile G, Mohebbi N, Moochhala SH, Oosterveld MJS, Prikhodina L, Hoppe B, Cochat P, Groothoff JW, and OxalEurope C (2022). Long-Term Transplantation Outcomes in Patients With Primary Hyperoxaluria Type 1 Included in the European Hyperoxaluria Consortium (OxalEurope) Registry. Kidney Int Rep7, 210-220. doi:10.1016/j.ekir.2021.11.006.
  • Birtel J, Spital G, Book M, Habbig S, Baumner S, Riehmer V, Beck BB, Rosenkranz D, Bolz HJ, Dahmer-Heath M, Herrmann P, Konig J, and Charbel Issa P (2021). NPHP1 gene-associated nephronophthisis is associated with an occult retinopathy. Kidney Int100, 1092-1100. doi:10.1016/j.kint.2021.06.012.
    • Fabretti F, Tschernoster N, Erger F, Hedergott A, Buescher AK, Dafinger C, Reusch B, Kontges VK, Kohl S, Bartram MP, Weber LT, Thiele H, Altmueller J, Schermer B, Beck BB, and Habbig S (2021). Expanding the Spectrum of FAT1 Nephropathies by Novel Mutations That Affect Hippo Signaling. Kidney Int Rep6, 1368-1378. doi:10.1016/j.ekir.2021.01.023.
    • Burgmaier K, Brinker L, Erger F, Beck BB, Benz MR, Bergmann C, Boyer O, Collard L, Dafinger C, Fila M, Kowalewska C, Lange-Sperandio B, Massella L, Mastrangelo A, Mekahli D, Miklaszewska M, Ortiz-Bruechle N, Patzer L, Prikhodina L, Ranchin B, Ranguelov N, Schild R, Seeman T, Sever L, Sikora P, Szczepanska M, Teixeira A, Thumfart J, Uetz B, Weber LT, Wühl E, Zerres K; ESCAPE Study group; GPN study group, Dötsch J, Schaefer F, Liebau MC; ARegPKD consortium. Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants. Kidney Int. 2021 Sep;100(3):650-659. doi: 10.1016/j.kint.2021.04.019.
    • Kolbuc M, Bienias B, Habbig S, Kolek MF, Szczepanska M, Kilis-Pstrusinska K, Wasilewska A, Adamczyk P, Motyka R, Tkaczyk M, Sikora P, Beck BB, and Zaniew M (2021). Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited. J Clin Med10. doi:10.3390/jcm10153265.
        • Schlingmann KP, Jouret F, Shen K, Nigam A, Arjona FJ, Dafinger C, Houillier P, Jones DP, Kleineruschkamp F, Oh J, Godefroid N, Eltan M, Guran T, Burtey S, Parotte MC, Konig J, Braun A, Bos C, Ibars Serra M, Rehmann H, Zwartkruis FJT, Renkema KY, Klingel K, Schulze-Bahr E, Schermer B, Bergmann C, Altmuller J, Thiele H, Beck BB, Dahan K, Sabatini D, Liebau MC, Vargas-Poussou R, Knoers N, Konrad M, and de Baaij JHF (2021). mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy. J Am Soc Nephrol32, 2885-2899. doi:10.1681/ASN.2021030333.
        • Asif M, Mocanu ID, Abdullah U, Hohne W, Altmuller J, Makhdoom EUH, Thiele H, Baig SM, Nurnberg P, Graul-Neumann L, and Hussain MS (2021). A novel missense variant of SCN4A co-segregates with congenital essential tremor in a consanguineous Kurdish family. Am J Med Genet A. doi:10.1002/ajmg.a.62610.
        • Bamborschke D, Ozdemir O, Kreutzer M, Motameny S, Thiele H, Kribs A, Dotsch J, Altmuller J, Nurnberg P, and Cirak S (2021). Ultra-rapid emergency genomic diagnosis of Donahue syndrome in a preterm infant within 17 hours. Am J Med Genet A185, 90-96. doi:10.1002/ajmg.a.61917.
        • Boehm V, Kueckelmann S, Gerbracht JV, Kallabis S, Britto-Borges T, Altmuller J, Kruger M, Dieterich C, and Gehring NH (2021). SMG5-SMG7 authorize nonsense-mediated mRNA decay by enabling SMG6 endonucleolytic activity. Nat Commun12, 3965. doi:10.1038/s41467-021-24046-3.
          • Daimaguler HS, Akpulat U, Ozdemir O, Yis U, Gungor S, Talim B, Diniz G, Baydan F, Thiele H, Altmuller J, Nurnberg P, and Cirak S (2021). Clinical and genetic characterization of PYROXD1-related myopathy patients from Turkey. Am J Med Genet A185, 1678-1690. doi:10.1002/ajmg.a.62148.
          • Flumann R, Rehkamper T, Nieper P, Pfeiffer P, Holzem A, Klein S, Bhatia S, Kochanek M, Kisis I, Pelzer BW, Ahlert H, Hauer J, da Palma Guerreiro A, Ryan JA, Reimann M, Riabinska A, Wiederstein J, Kruger M, Deckert M, Altmuller J, Klatt AR, Frenzel LP, Pasqualucci L, Beguelin W, Melnick AM, Sander S, Montesinos-Rongen M, Brunn A, Lohneis P, Buttner R, Kashkar H, Borkhardt A, Letai A, Persigehl T, Peifer M, Schmitt CA, Reinhardt HC, and Knittel G (2021). An Autochthonous Mouse Model of Myd88- and BCL2-Driven Diffuse Large B-cell Lymphoma Reveals Actionable Molecular Vulnerabilities. Blood Cancer Discov2, 70-91. doi:10.1158/2643-3230.BCD-19-0059.
          • Gabriel E, Albanna W, Pasquini G, Ramani A, Josipovic N, Mariappan A, Schinzel F, Karch CM, Bao G, Gottardo M, Suren AA, Hescheler J, Nagel-Wolfrum K, Persico V, Rizzoli SO, Altmuller J, Riparbelli MG, Callaini G, Goureau O, Papantonis A, Busskamp V, Schneider T, and Gopalakrishnan J (2021). Human brain organoids assemble functionally integrated bilateral optic vesicles. Cell Stem Cell28, 1740-1757 e1748. doi:10.1016/j.stem.2021.07.010.
          • Gizak A, Diegmann S, Dreha-Kulaczewski S, Wisniewski J, Duda P, Ohlenbusch A, Huppke B, Henneke M, Hohne W, Altmuller J, Thiele H, Nurnberg P, Rakus D, Gartner J, and Huppke P (2021). A novel remitting leukodystrophy associated with a variant in FBP2. Brain Commun3, fcab036. doi:10.1093/braincomms/fcab036.
          • Iqbal M, Maroofian R, Cavdarli B, Riccardi F, Field M, Banka S, Bubshait DK, Li Y, Hertecant J, Baig SM, Dyment D, Efthymiou S, Abdullah U, Makhdoom EUH, Ali Z, Scherf de Almeida T, Molinari F, Mignon-Ravix C, Chabrol B, Antony J, Ades L, Pagnamenta AT, Jackson A, Douzgou S, Genomics England Research C, Beetz C, Karageorgou V, Vona B, Rad A, Baig JM, Sultan T, Alvi JR, Maqbool S, Rahman F, Toosi MB, Ashrafzadeh F, Imannezhad S, Karimiani EG, Sarwar Y, Khan S, Jameel M, Noegel AA, Budde B, Altmuller J, Motameny S, Hohne W, Houlden H, Nurnberg P, Wollnik B, Villard L, Alkuraya FS, Osmond M, Hussain MS, and Yigit G (2021). Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies. Genet Med23, 2138-2149. doi:10.1038/s41436-021-01260-4.
          • Kargapolova Y, Rehimi R, Kayserili H, Bruhl J, Sofiadis K, Zirkel A, Palikyras S, Mizi A, Li Y, Yigit G, Hoischen A, Frank S, Russ N, Trautwein J, van Bon B, Gilissen C, Laugsch M, Gusmao EG, Josipovic N, Altmuller J, Nurnberg P, Langst G, Kaiser FJ, Watrin E, Brunner H, Rada-Iglesias A, Kurian L, Wollnik B, Bouazoune K, and Papantonis A (2021). Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology. Nat Commun12, 3014. doi:10.1038/s41467-021-23327-1.
          • Koester J, Miroshnikova YA, Ghatak S, Chacon-Martinez CA, Morgner J, Li X, Atanassov I, Altmuller J, Birk DE, Koch M, Bloch W, Bartusel M, Niessen CM, Rada-Iglesias A, and Wickstrom SA (2021). Niche stiffening compromises hair follicle stem cell potential during ageing by reducing bivalent promoter accessibility. Nat Cell Biol23, 771-781. doi:10.1038/s41556-021-00705-x.
          • Lessel D, Rading K, Campbell SE, Thiele H, Altmuller J, Gordon LB, and Kubisch C (2022). A novel homozygous synonymous variant further expands the phenotypic spectrum of POLR3A-related pathologies. Am J Med Genet A188, 216-223. doi:10.1002/ajmg.a.62525.
          • Makhdoom EUH, Waseem SS, Iqbal M, Abdullah U, Hussain G, Asif M, Budde B, Hohne W, Tinschert S, Saadi SM, Yousaf H, Ali Z, Fatima A, Kaygusuz E, Khan A, Jameel M, Khan S, Tariq M, Anjum I, Altmuller J, Thiele H, Honing S, Baig SM, Nurnberg P, and Hussain MS (2021). Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ. Genes (Basel)12. doi:10.3390/genes12050731.
          • Pacholewska A, Grimm C, Herling CD, Lienhard M, Konigs A, Timmermann B, Altmuller J, Mucke O, Reinhardt HC, Plass C, Herwig R, Hallek M, and Schweiger MR (2021). Altered DNA Methylation Profiles in SF3B1 Mutated CLL Patients. Int J Mol Sci22. doi:10.3390/ijms22179337.
          • Perne C, Peters S, Cartolano M, Horpaopan S, Grimm C, Altmuller J, Sommer AK, Hillmer AM, Thiele H, Odenthal M, Moslein G, Adam R, Sivalingam S, Kirfel J, Schweiger MR, Peifer M, Spier I, and Aretz S (2021). Variant profiling of colorectal adenomas from three patients of two families with MSH3-related adenomatous polyposis. PLoS One16, e0259185. doi:10.1371/journal.pone.0259185.
          • Rosswog C, Bartenhagen C, Welte A, Kahlert Y, Hemstedt N, Lorenz W, Cartolano M, Ackermann S, Perner S, Vogel W, Altmuller J, Nurnberg P, Hertwig F, Gohring G, Lilienweiss E, Stutz AM, Korbel JO, Thomas RK, Peifer M, and Fischer M (2021). Chromothripsis followed by circular recombination drives oncogene amplification in human cancer. Nat Genet53, 1673-1685. doi:10.1038/s41588-021-00951-7.
          • Schaufler D, Ast DF, Tumbrink HL, Abedpour N, Maas L, Schwabe AE, Spille I, Lennartz S, Fassunke J, Aldea M, Besse B, Planchard D, Nogova L, Michels S, Kobe C, Persigehl T, Westphal T, Koleczko S, Fischer R, Weber JP, Altmuller J, Thomas RK, Merkelbach-Bruse S, Gautschi O, Mezquita L, Buttner R, Wolf J, Peifer M, Bragelmann J, Scheffler M, and Sos ML (2021). Clonal dynamics of BRAF-driven drug resistance in EGFR-mutant lung cancer. NPJ Precis Oncol5, 102. doi:10.1038/s41698-021-00241-9.
          • Schmidt J, Schreiber G, Altmuller J, Thiele H, Nurnberg P, Li Y, Kaulfuss S, Funke R, Wilken B, Yigit G, and Wollnik B (2021). Familial cleft tongue caused by a unique translation initiation codon variant in TP63. Eur J Hum Genet. doi:10.1038/s41431-021-00967-x.
          • Schmidt J, Goergens J, Pochechueva T, Kotter A, Schwenzer N, Sitte M, Werner G, Altmuller J, Thiele H, Nurnberg P, Isensee J, Li Y, Muller C, Leube B, Reinhardt HC, Hucho T, Salinas G, Helm M, Jachimowicz RD, Wieczorek D, Kohl T, Lehnart SE, Yigit G, and Wollnik B (2021). Biallelic variants in YRDC cause a developmental disorder with progeroid features. Hum Genet140, 1679-1693. doi:10.1007/s00439-021-02347-3.
          • Schroder S, Li Y, Yigit G, Altmuller J, Bader I, Bevot A, Biskup S, Dreha-Kulaczewski S, Christoph Korenke G, Kottke R, Mayr JA, Preisel M, Toelle SP, Wente-Schulz S, Wortmann SB, Hahn H, Boltshauser E, Uhmann A, Wollnik B, and Brockmann K (2021). Heterozygous truncating variants in SUFU cause congenital ocular motor apraxia. Genet Med23, 341-351. doi:10.1038/s41436-020-00979-w.
          • Sofiadis K, Josipovic N, Nikolic M, Kargapolova Y, Ubelmesser N, Varamogianni-Mamatsi V, Zirkel A, Papadionysiou I, Loughran G, Keane J, Michel A, Gusmao EG, Becker C, Altmuller J, Georgomanolis T, Mizi A, and Papantonis A (2021). HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence. Mol Syst Biol17, e9760. doi:10.15252/msb.20209760.
          • Talyan S, Filipow S, Ignarski M, Smieszek M, Chen H, Kuhne L, Butt L, Gobel H, Hoyer-Allo KJR, Koehler FC, Altmuller J, Brinkkotter P, Schermer B, Benzing T, Kann M, Muller RU, and Dieterich C (2021). CALINCA-A Novel Pipeline for the Identification of lncRNAs in Podocyte Disease. Cells10. doi:10.3390/cells10030692.
          • Theobald SJ, Simonis A, Georgomanolis T, Kreer C, Zehner M, Eisfeld HS, Albert MC, Chhen J, Motameny S, Erger F, Fischer J, Malin JJ, Grab J, Winter S, Pouikli A, David F, Boll B, Koehler P, Vanshylla K, Gruell H, Suarez I, Hallek M, Fatkenheuer G, Jung N, Cornely OA, Lehmann C, Tessarz P, Altmuller J, Nurnberg P, Kashkar H, Klein F, Koch M, and Rybniker J (2021). Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Mol Med13, e14150. doi:10.15252/emmm.202114150.
          • Warnat-Herresthal S, Schultze H, Shastry KL, Manamohan S, Mukherjee S, Garg V, Sarveswara R, Handler K, Pickkers P, Aziz NA, Ktena S, Tran F, Bitzer M, Ossowski S, Casadei N, Herr C, Petersheim D, Behrends U, Kern F, Fehlmann T, Schommers P, Lehmann C, Augustin M, Rybniker J, Altmuller J, Mishra N, Bernardes JP, Kramer B, Bonaguro L, Schulte-Schrepping J, De Domenico E, Siever C, Kraut M, Desai M, Monnet B, Saridaki M, Siegel CM, Drews A, Nuesch-Germano M, Theis H, Heyckendorf J, Schreiber S, Kim-Hellmuth S, Study C-A, Nattermann J, Skowasch D, Kurth I, Keller A, Bals R, Nurnberg P, Riess O, Rosenstiel P, Netea MG, Theis F, Mukherjee S, Backes M, Aschenbrenner AC, Ulas T, Deutsche C-OI, Breteler MMB, Giamarellos-Bourboulis EJ, Kox M, Becker M, Cheran S, Woodacre MS, Goh EL, and Schultze JL (2021). Swarm Learning for decentralized and confidential clinical machine learning. Nature594, 265-270. doi:10.1038/s41586-021-03583-3.
          • Weng PL, Majmundar AJ, Khan K, Lim TY, Shril S, Jin G, Musgrove J, Wang M, Ahram DF, Aggarwal VS, Bier LE, Heinzen EL, Onuchic-Whitford AC, Mann N, Buerger F, Schneider R, Deutsch K, Kitzler TM, Klambt V, Kolb A, Mao Y, Moufawad El Achkar C, Mitrotti A, Martino J, Beck BB, Altmuller J, Benz MR, Yano S, Mikati MA, Gunduz T, Cope H, Shashi V, Undiagnosed Diseases N, Trachtman H, Bodria M, Caridi G, Pisani I, Fiaccadori E, AbuMaziad AS, Martinez-Agosto JA, Yadin O, Zuckerman J, Kim A, Center UCG, John-Kroegel U, Tyndall AV, Parboosingh JS, Innes AM, Bierzynska A, Koziell AB, Muorah M, Saleem MA, Hoefele J, Riedhammer KM, Gharavi AG, Jobanputra V, Pierce-Hoffman E, Seaby EG, O'Donnell-Luria A, Rehm HL, Mane S, D'Agati VD, Pollak MR, Ghiggeri GM, Lifton RP, Goldstein DB, Davis EE, Hildebrandt F, and Sanna-Cherchi S (2021). De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis. Am J Hum Genet108, 357-367. doi:10.1016/j.ajhg.2021.01.008.
          • Zhang S, Ubelmesser N, Josipovic N, Forte G, Slotman JA, Chiang M, Gothe HJ, Gusmao EG, Becker C, Altmuller J, Houtsmuller AB, Roukos V, Wendt KS, Marenduzzo D, and Papantonis A (2021). RNA polymerase II is required for spatial chromatin reorganization following exit from mitosis. Sci Adv7, eabg8205. doi:10.1126/sciadv.abg8205.
          • Butt L, Unnersjo-Jess D, Hohne M, Edwards A, Binz-Lotter J, Reilly D, Hahnfeldt R, Ziegler V, Fremter K, Rinschen MM, Helmstadter M, Ebert LK, Castrop H, Hackl MJ, Walz G, Brinkkoetter PT, Liebau MC, Tory K, Hoyer PF, Beck BB, Brismar H, Blom H, Schermer B, and Benzing T (2020). A molecular mechanism explaining albuminuria in kidney disease. Nature metabolism 2, 461-74.
          • Koehler S, Kuczkowski A, Kuehne L, Jungst C, Hoehne M, Grahammer F, Eddy S, Kretzler M, Beck BB, Hohfeld J, Schermer B, Benzing T, Brinkkoetter PT, and Rinschen MM (2020). Proteome Analysis of Isolated Podocytes Reveals Stress Responses in Glomerular Sclerosis. J Am Soc Nephrol 31, 544-59.
             
          • Kolbuc M, Lessmeier L, Salamon-Slowinska D, Malecka I, Pawlaczyk K, Walkowiak J, Wysocki J, Beck BB, and Zaniew M (2020). Hypomagnesemia is underestimated in children with HNF1B mutations. Pediatr Nephrol 10.1007/s00467-020-04576-6.
             
          • Sikora P, Zaniew M, Grenda R, Jobs K, Rubik J, Zawadzki J, Myślak M, Durlik M, Erger F, Bieniaś B, Hoppe B, Beck BB. Still diagnosed too late and under-recognized? The first comprehensive report on primary hyperoxaluria in Poland. Pol Arch Intern Med. 2020 Dec 22;130(12):1053-1063. doi: 10.20452/pamw.15698.
          • Taylan C, Wenzel A, Erger F, Gobel H, Weber LT, and Beck BB (2020). Case Report: Exome Sequencing Reveals LRBA Deficiency in a Patient With End-Stage Renal Disease. Front Pediatr 8, 42.
          • Zivna M, Kidd K, Zaidan M, Vyletal P, Baresova V, Hodanova K, Sovova J, Hartmannova H, Votruba M, Treslova H, Jedlickova I, Sikora J, Hulkova H, Robins V, Hnizda A, Zivny J, Papagregoriou G, Mesnard L, Beck BB, Wenzel A, Tory K, Haeffner K, Wolf MTF, Bleyer ME, Sayer JA, Ong ACM, Balogh L, Jakubowska A, Laszkiewicz A, Clissold R, Shaw-Smith C, Munshi R, Haws RM, Izzi C, Capelli I, Santostefano M, Graziano C, Scolari F, Sussman A, Trachtman H, Decramer S, Matignon M, Grimbert P, Shoemaker LR, Stavrou C, Abdelwahed M, Belghith N, Sinclair M, Claes K, Kopel T, Moe S, Deltas C, Knebelmann B, Rampoldi L, Kmoch S, and Bleyer AJ (2020). An International Cohort Study of Autosomal Dominant Tubulointerstitial Kidney Disease due to REN Mutations Identifies Distinct Clinical Subtypes. Kidney Int 10.1016/j.kint.2020.06.041.
          • Budde BS, Aly MA, Mohamed MR, Bress A, Altmuller J, Motameny S, Kawalia A, Thiele H, Konrad K, Becker C, Toliat MR, Nurnberg G, Sayed EAF, Mohamed ES, Pfister M, and Nurnberg P (2020). Comprehensive molecular analysis of 61 Egyptian families with hereditary nonsyndromic hearing loss. Clin Genet. doi:10.1111/cge.13754.
          • Erger F, Norling D, Borchert D, Leenen E, Habbig S, Wiesener MS, Bartram MP, Wenzel A, Becker C, Toliat MR, Nurnberg P, Beck BB, and Altmuller J (2020). cfNOMe - A single assay for comprehensive epigenetic analyses of cell-free DNA. Genome Med12, 54. doi:10.1186/s13073-020-00750-5.
          • Gerbracht JV, Boehm V, Britto-Borges T, Kallabis S, Wiederstein JL, Ciriello S, Aschemeier DU, Kruger M, Frese CK, Altmuller J, Dieterich C, and Gehring NH (2020). CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex. Nucleic Acids Res48, 8626-8644. doi:10.1093/nar/gkaa564.
          • Hackl A, Erger F, Skerka C, Wenzel A, Tschernoster N, Ehren R, Burgmaier K, Riehmer V, Licht C, Kirschfink M, Weber LT, Altmueller J, Zipfel PF, Habbig S. Long-term data on two sisters with C3GN due to an identical, homozygous CFH mutation and autoantibodies. Clin Nephrol. 2020 Oct;94(4):197-206. doi: 10.5414/CN110135.
          • Hauke J, Harter P, Ernst C, Burges A, Schmidt S, Reuss A, Borde J, De Gregorio N, Dietrich D, El-Balat A, Kayali M, Gevensleben H, Hilpert F, Altmuller J, Heimbach A, Meier W, Schoemig-Markiefka B, Thiele H, Kimmig R, Nurnberg P, Kast K, Richters L, Sehouli J, Schmutzler RK, and Hahnen E (2020). Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in BRCA1/2: results of the observational AGO-TR1 study (NCT02222883). J Med Genet. doi:10.1136/jmedgenet-2020-107353.
          • Jiang H, Gallet S, Klemm P, Scholl P, Folz-Donahue K, Altmuller J, Alber J, Heilinger C, Kukat C, Loyens A, Muller-Fielitz H, Sundaram S, Schwaninger M, Prevot V, and Bruning JC (2020). MCH Neurons Regulate Permeability of the Median Eminence Barrier. Neuron. doi:10.1016/j.neuron.2020.04.020.
          • Johnsen M, Kubacki T, Yeroslaviz A, Spath MR, Morsdorf J, Gobel H, Bohl K, Ignarski M, Meharg C, Habermann B, Altmuller J, Beyer A, Benzing T, Schermer B, Burst V, and Muller RU (2020). The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury. J Am Soc Nephrol31, 716-730. doi:10.1681/ASN.2019050534.
          • Kramer M, Plum PS, Velazquez Camacho O, Folz-Donahue K, Thelen M, Garcia-Marquez I, Wolwer C, Busker S, Wittig J, Franitza M, Altmuller J, Loser H, Schlosser H, Buttner R, Schroder W, Bruns CJ, Alakus H, Quaas A, Chon SH, and Hillmer AM (2020). Cell type-specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics. Mol Oncol14, 1170-1184. doi:10.1002/1878-0261.12680.
          • Oberbeck S, Schrader A, Warner K, Jungherz D, Crispatzu G, von Jan J, Chmielewski M, Ianevski A, Diebner HH, Mayer P, Kondo Ados A, Wahnschaffe L, Braun T, Muller TA, Wagle P, Bouska A, Neumann T, Putzer S, Varghese L, Pflug N, Thelen M, Makalowski J, Riet N, Gox HJM, Rappl G, Altmuller J, Kotrova M, Persigehl T, Hopfinger G, Hansmann ML, Schlosser H, Stilgenbauer S, Durig J, Mougiakakos D, von Bergwelt-Baildon M, Roeder I, Hartmann S, Hallek M, Moriggl RH, Bruggemann M, Aittokallio T, Iqbal J, Newrzela S, Abken H, and Herling M (2020). Non-canonical effector functions of the T-memory-like T-PLL cell are shaped by cooperative TCL1A and TCR signaling. Blood. doi:10.1182/blood.2019003348.
          • Patil P, Cieslak A, Bernhart SH, Toprak UH, Wagener R, Lopez C, Wiehle L, Bens S, Altmuller J, Franitza M, Scholz I, Jayne S, Ahearne MJ, Scheffold A, Jebaraj BMC, Schneider C, Costa D, Braun T, Schrader A, Campo E, Dyer MJS, Nurnberg P, Durig J, Johansson P, Bottcher S, Schlesner M, Herling M, Stilgenbauer S, Macintyre E, and Siebert R (2020). Reconstruction of rearranged T-cell receptor loci by whole genome and transcriptome sequencing gives insights into the initial steps of T-cell prolymphocytic leukemia. Genes Chromosomes Cancer59, 261-267. doi:10.1002/gcc.22821.
          • Pergande M, Motameny S, Ozdemir O, Kreutzer M, Wang H, Daimaguler HS, Becker K, Karakaya M, Ehrhardt H, Elcioglu N, Ostojic S, Chao CM, Kawalia A, Duman O, Koy A, Hahn A, Reimann J, Schoner K, Schanzer A, Westhoff JH, Schwaibold EMC, Cossee M, Imbert-Bouteille M, von Pein H, Haliloglu G, Topaloglu H, Altmuller J, Nurnberg P, Thiele H, Heller R, and Cirak S (2020). The genomic and clinical landscape of fetal akinesia. Genet Med22, 511-523. doi:10.1038/s41436-019-0680-1.
          • Pohl-Rescigno E, Hauke J, Loibl S, Mobus V, Denkert C, Fasching PA, Kayali M, Ernst C, Weber-Lassalle N, Hanusch C, Tesch H, Muller V, Altmuller J, Thiele H, Untch M, Lubbe K, Nurnberg P, Rhiem K, Furlanetto J, Lederer B, Jackisch C, Nekljudova V, Schmutzler RK, Schneeweiss A, and Hahnen E (2020). Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer: A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol. doi:10.1001/jamaoncol.2020.0007.
          • Sauvigny T, Alawi M, Krause L, Renner S, Spohn M, Busch A, Kolbe V, Altmuller J, Loscher BS, Franke A, Brockmann C, Lieb W, Westphal M, Schmidt NO, Regelsberger J, and Rosenberger G (2020). Exome sequencing in 38 patients with intracranial aneurysms and subarachnoid hemorrhage. J Neurol. doi:10.1007/s00415-020-09865-6.
          • Ufartes R, Berger H, Till K, Salinas G, Sturm M, Altmuller J, Nurnberg P, Thiele H, Funke R, Apeshiotis N, Langen H, Wollnik B, Borchers A, and Pauli S (2020). De novo mutations in FBRSL1 cause a novel recognizable malformation and intellectual disability syndrome. Hum Genet. doi:10.1007/s00439-020-02175-x.
          • Yigit G, Saida K, DeMarzo D, Miyake N, Fujita A, Yang Tan T, White SM, Wadley A, Toliat MR, Motameny S, Franitza M, Stutterd CA, Chong PF, Kira R, Sengoku T, Ogata K, Guillen Sacoto MJ, Fresen C, Beck BB, Nurnberg P, Dieterich C, Wollnik B, Matsumoto N, and Altmuller J (2020). The recurrent postzygotic pathogenic variant p.Glu47Lys in RHOA causes a novel recognizable neuroectodermal phenotype. Hum Mutat41, 591-599. doi:10.1002/humu.23964.
          • Burgmaier K, Ariceta G, Bald M, Buescher AK, Burgmaier M, Erger F, Gessner M, Gokce I, Konig J, Kowalewska C, Massella L, Mastrangelo A, Mekahli D, Pape L, Patzer L, Potemkina A, Schalk G, Schild R, Shroff R, Szczepanska M, Taranta-Janusz K, Tkaczyk M, Weber LT, Wuhl E, Wurm D, Wygoda S, Zagozdzon I, Dotsch J, Oh J, Schaefer F, Liebau MC, and consortium AR (2020). Severe neurological outcomes after very early bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD). Sci Rep10, 16025. doi:10.1038/s41598-020-71956-1.
          PD Dr. Bodo Beck CMMC Cologne
          PD Dr. Bodo Beck

          Institute of Human Genetics - CMMC Research Building

          CMMC - PI - assoc. RG 03

          +49 221 478 86824

          +49 221 478 97835

          Institute of Human Genetics - CMMC Research Building

          Robert-Koch-Str. 21

          50931 Cologne

          https://humangenetik.uk-koeln.de/en/research/rare-and-hereditary-kidney-diseases-working-group/

          CMMC Profile Page

          Curriculum Vitae (CV)

          Publications - Bodo Beck

          Link to PubMed

          Dr. Janine Altmüller CMMC Cologne
          Dr. Janine Altmüller

          CMMC & Genomics Berlin Inst. of Health - Charité Berlin

          CMMC - PI - assoc. RG 31
          CMMC - Co-PI - assoc. RG 03

          CMMC & Genomics Berlin Inst. of Health - Charité Berlin

          c/o head of genomics Berlin Institute of Health at Charité – Universitätsmedizin Berlin Max Delbrück Center for Molecular Medicine

          13125 Berlin

          https://www.mdc-berlin.de/genomics

          CMMC Profile Page

          Curriculum Vitae (CV)

          Publications on PubMed

          Publications - Janine Altmüller

          Link to PubMed

          Dr. Florian Erger CMMC Cologne
          Dr. Florian Erger

          Institute of Human Genetics - CMMC Research Building

          CMMC - Co-PI - assoc. RG 03

          +49 221 478 86828

          Institute of Human Genetics - CMMC Research Building

          Robert-Koch-Str. 21

          50931 Cologne

          CMMC Profile Page

          Curriculum Vitae (CV)

          Publications on PubMed

          Publications - Florian Erger

          Link to PubMed

          Group Members

          Andrea Wenzel (PostDoc)
          Björn Reusch (PhD student)
          Nikolai Tschernoster (PhD student)