Center for Molecular Medicine Cologne

Beck, Bodo - 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.

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
PD Dr. Bodo Beck CMMC Cologne
PD Dr. Bodo Beck

Center for Molecular Medicine Cologne | Institute of Human Genetics | CMMC Research Building

CMMC - PI - assoc. RG 03

+49 221 478 86824

+49 221 478 97835

Center for Molecular Medicine Cologne | 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

Center for Moleculare Medicine

CMMC - Co-PI - assoc. RG 03

Center for Moleculare Medicine

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

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

Curriculum Vitae (CV)

Publications on PubMed

Publications - Janine Altmüller

Link to PubMed

Dr. Florian Erger CMMC Cologne
Dr. Florian Erger

Center for Molecular Medicine Cologne | Institute of Human Genetics | CMMC Research Building

CMMC - Co-PI - assoc. RG 03

+49 221 478 86828

Center for Molecular Medicine Cologne | 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

Figure 1
Group Members

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