Center for Molecular Medicine Cologne

Schermer, Bernhard | Liebau, Max C - C 14

Discovering novel diseases mechanisms of human ciliopathies using proximity labelling technologies

Introduction

The overarching aim of our project is to gain novel insights in the disease mechanisms of a large heterogeneous group of severe human diseases termed ciliopathies.

While individual ciliopathies are rare conditions, they collectively struck a large number of individuals. We expect our studies to challenge and expand several current pathophysiological concepts in the large field of ciliopathy research.

This will be important for many medical disciplines since ciliopathies manifest in multiple organs (e.g. kidney, brain, eyes, pancreas, liver). Ultimately, we hope to provide novel key mechanisms and potential therapeutic targets to the pathogenesis of ciliopathies.

Groundbreaking work of the last two decades has revealed that mutations in genes encoding for proteins localized to primary cilia are causative for a large number of different human diseases, nowadays subsumed as a group termed ciliopathies.

A hallmark of most ciliopathies is the development of cystic kidneys caused by altered function and proliferation of epithelial cells. Multiple other tissues can also be severely affected. Beyond hereditary ciliopathies, there is accumulating evidence that cilia may be involved in the pathogenesis of various acquired diseases including diabetes and cancer.

Primary cilia are sensory organelles that, like antennae, project from the surface of virtually all mammalian cells explaining the broad spectrum of defects and clinical symptoms observed in ciliopathies. To exert their signaling functions, cilia are covered by a specialized compartment of the plasma membrane and the entry of proteins into the ciliary compartment and the ciliary membrane is strictly regulated.

While basic mechanisms of ciliogenesis, ciliary disassembly, ciliary targeting, intra-flagellar transport and ‘classical’ ciliary signaling such as Hedgehog or WNT signaling have been extensively studied in the recent past, the exact molecular alterations of primary cilia in human ciliopathies have not been identified so far due to technical limitations. Since the vast majority of ciliopathy-causing mutations do not result in the loss of ciliogenesis, a detailed understanding of the subtle and largely unknown alterations of cilia in ciliopathies is urgently needed to decipher the mechanisms of disease.

To break down technical limitations in studying ciliary protein composition we fused the engineered peroxidase APEX2 to a ciliary targeting motiv and used proximity labeling and pulldowns followed by MS/MS analyses to explore the ciliary membrane associated proteome.

This approach revealed numerous novel ciliary proteins unexpectedly including actin-binding proteins and even more unforeseen families of proteins.

The overarching goal of the at hand project is to use and expand this technology to get a deeper understanding of the molecular composition of cilia and their alterations in ciliopathies both in patient derived cells and model organisms.

Previous Work

To overcome limitations in the analysis of the ciliary proteome we used APEX-based proximity labeling1 to biotinylate and pull down ciliary membrane associated proteins for subsequent MS/MS analysis (‘ciliary membrane APEX’ (cmAPEX);2). With this approach we identified numerous novel ciliary proteins in renal epithelial cells. Among those we found actin binding proteins to be very prominent. Following up on this, we could demonstrate that myosin 5a is essential for ciliogenesis by using knockout (KO) cell lines generated with CRISPR/Cas9. This function has been confirmed independently by another lab.3

We recently used the same experimental approach to study ciliary disassembly. In brief, we induced ciliogenesis by serum starvation for 48 h and stimulated ciliary disassembly by serum addition. The ciliary proteome was determined at 45 min, 2 h and 8 h after serum addition. Interestingly, within these datasets, a number of proteins related to unexpected biological processes were detectable with an increased abundance. We are currently following up on these hits and hope to obtain a deeper understanding of the interplay of cilia with other processes and structures of cellular biology. In summary, ciliary proximity labeling allows the comprehensively analysis of the ciliary proteome with very high sensitivity and provided some more evidence on a potential role of cilia in cellular biology.

References

  1. Rhee H-W, Zou P, Udeshi ND, et al. Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science 2013;339(6125):1328–31.
  2. Kohli P, Höhne M, Jüngst C, et al. The ciliary membrane-associated proteome reveals actin-binding proteins as key components of cilia. EMBO Rep 2017;18(9):1521–35.
  3. Wu C-T, Chen H-Y, Tang TK. Myosin-Va is required for preciliary vesicle transportation to the mother centriole during ciliogenesis. Nat Cell Biol 2018;20(2):175–85.
  1. Jain, M., Kaiser, R.W.J., Bohl, K., Hoehne, M., Gobel, H., Bartram, M.P., Habbig, S., Muller, R.U., Fogo, A.B., Benzing, T., Schermer, B., Hopker, K., and Slaats, G.G.: Inactivation of Apoptosis Antagonizing Transcription Factor in tubular epithelial cells induces accumulation of DNA damage and nephronophthisis. Kidney Int. (2019);  95: 846-858.
  2. Dafinger, C., Rinschen, M.M., Borgal, L., Ehrenberg, C., Basten, S.G., Franke, M., Hohne, M., Rauh, M., Gobel, H., Bloch, W., Wunderlich, F.T., Peters, D.J.M., Tasche, D., Mishra, T., Habbig, S., Dotsch, J., Muller, R.U., Bruning, J.C., Persigehl, T., Giles, R.H., Benzing, T., Schermer, B.*, and Liebau, M.C.*: Targeted deletion of the AAA-ATPase Ruvbl1 in mice disrupts ciliary integrity and causes renal disease and hydrocephalus. Exp Mol Med. (2018);  50: 75.  (*equal contribution)
  3. Burgmaier K, Kunzmann K, Ariceta G, Bergmann C, Buescher AK, Burgmaier M, Dursun I, Duzova A, Eid L, Feldkoetter M, Gessner M, Gokce I, Haffner D, Hooman N, Hoppe B, Jankauskiene A, Klaus G, König J, Litwin M, Massella L, Mekahli D, Melek E, Mir S, Pape L, Prikhodina L, Ranchin B, Schild R, Seeman T, Sever L, Shroff R, Soliman NA, Stabouli S, Stanczyk M, Tabel Y, Taranta-Janusz K, Testa S, Thumfart J, Topaloglu R, Weber LT, Wicher D, Wühl E, Wygoda S, Yilmaz A, Zachwieja K, Zagozdzon I, Zerres K, ESCAPE Study Group, GPN Study Group, Dötsch J, Schaefer F, Liebau MC for the ARegPKD consortium. “Risk Factors for Early Dialysis Dependency in ARPKD”; J Peds 2018 Aug;199:22-28.e6.
  4. Höhne M, Frese CK, Grahammer F, Dafinger C, Ciarimboli G, Butt L, Binz J, Hackl MJ, Rahmatollahi M, Kann M, Schneider S, Altintas MM, Schermer B, Reinheckel T, Göbel H, Reiser J, Huber TB, Kramann R, Seeger-Nukpezah T, Liebau MC, Beck BB, Benzing T, Beyer A, Rinschen MM. “Individual nephron proteomes connect morphology and function in proteinuric kidney disease”; Kidney Int 2018 Jun;93(6):1308-1319.
  5. Rinschen, M.M., Grahammer, F., Hoppe, A.K., Kohli, P., Hagmann, H., Kretz, O., Bertsch, S., Hohne, M., Gobel, H., Bartram, M.P., Gandhirajan, R.K., Kruger, M., Brinkkoetter, P.T., Huber, T.B., Kann, M., Wickstrom, S.A., Benzing, T., and Schermer, B.: YAP-mediated mechanotransduction determines the podocyte's response to damage. Sci Signal. (2017);  10.
  6. Kohli, P., Hohne, M., Jungst, C., Bertsch, S., Ebert, L.K., Schauss, A.C., Benzing, T., Rinschen, M.M., and Schermer, B.: The ciliary membrane-associated proteome reveals actin-binding proteins as key components of cilia. EMBO Rep. (2017);  18: 1521-1535.
  7. Gandhirajan, R.K., Jain, M., Walla, B., Johnsen, M., Bartram, M.P., Huynh Anh, M., Rinschen, M.M., Benzing, T., and Schermer, B.: Cysteine S-Glutathionylation Promotes Stability and Activation of the Hippo Downstream Effector Transcriptional Co-activator with PDZ-binding Motif (TAZ). J Biol Chem. (2016);  291: 11596-607.
  8. Borgal, L., Rinschen, M.M., Dafinger, C., Liebrecht, V.I., Abken, H., Benzing, T., and Schermer, B.: Jade-1S phosphorylation induced by CK1alpha contributes to cell cycle progression. Cell Cycle. (2016);  15: 1034-45.
  9. Kohli, P., Bartram, M.P., Habbig, S., Pahmeyer, C., Lamkemeyer, T., Benzing, T., Schermer, B.*, and Rinschen, M.M.*: Label-free quantitative proteomic analysis of the YAP/TAZ interactome. Am J Physiol Cell Physiol. (2014);  306: C805-18. (*equal contribution)
  10. Borgal, L., Rinschen, M.M., Dafinger, C., Hoff, S., Reinert, M.J., Lamkemeyer, T., Lienkamp, S.S., Benzing, T., and Schermer, B.: Casein kinase 1 alpha phosphorylates the Wnt regulator Jade-1 and modulates its activity. J Biol Chem. (2014);  289: 26344-56.
  • Koehler, FC, Fu, CY, Spath, MR, Hoyer-Allo, KJR, Bohl, K, Gobel, H, Lackmann, JW, Grundmann, F, Osterholt, T, Gloistein, C, Steiner, JD, Antebi, A, Benzing, T, Schermer, B, Schwarz, G, Burst, V, and Muller, RU (2022) A systematic analysis of diet-induced nephroprotection reveals overlapping changes in cysteine catabolism. Transl Res.
  • Koehler S, Odenthal J, Ludwig V, Unnersjo Jess D, Hohne M, Jungst C, Grawe F, Helmstadter M, Janku JL, Bergmann C, Hoyer PF, Hagmann HH, Walz G, Bloch W, Niessen C, Schermer B, Wodarz A, Denholm B, Benzing T, Iden S, and Brinkkoetter PT (2022). Scaffold polarity proteins Par3A and Par3B share redundant functions while Par3B acts independent of atypical protein kinase C/Par6 in podocytes to maintain the kidney filtration barrier. Kidney Int101, 733-751. doi:10.1016/j.kint.2021.11.030.
  • Kroef, V, Ruegenberg, S, Horn, M, Allmeroth, K, Ebert, L, Bozkus, S, Miethe, S, Elling, U, Schermer, B, Baumann, U, and Denzel, MS (2022) GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosamine pathway. Elife,  11.
  • Butt L, Unnersjo-Jess D, Hohne M, Hahnfeldt R, Reilly D, Rinschen MM, Plagmann I, Diefenhardt P, Brahler S, Brinkkotter PT, Brismar H, Blom H, Schermer B, and Benzing T (2022). Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular Disease. J Am Soc Nephrol33, 138-154. doi:10.1681/ASN.2020060858.
  • Hoyer-Allo KJR, Spath MR, Brodesser S, Zhu Y, Binz-Lotter J, Hohne M, Broenneke H, Bohl K, Johnsen M, Kubacki T, Kiefer K, Seufert L, Koehler FC, Grundmann F, Hackl MJ, Schermer B, Bruning J, Benzing T, Burst V, and Muller RU (2022). Caloric restriction reduces the pro-inflammatory eicosanoid 20-hydroxyeicosatetraenoic acid to protect from acute kidney injury. Kidney Int. doi:10.1016/j.kint.2022.04.033.
  • 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.
  • Unnersjo-Jess D, Ramdedovic A, Hohne M, Butt L, Koehler FC, Muller RU, Hoyer PF, Blom H, Schermer B, and Benzing T (2022). Three-Dimensional Super-Resolved Imaging of Paraffin-Embedded Kidney Samples. Kidney3603, 446-454. doi:10.34067/KID.0005882021.
  • Kaczmarek AT, Bender D, Gehling T, Kohl JB, Daimaguler HS, Santamaria-Araujo JA, Liebau MC, Koy A, Cirak S, and Schwarz G (2022). A defect in molybdenum cofactor binding causes an attenuated form of sulfite oxidase deficiency. J Inherit Metab Dis45, 169-182. doi:10.1002/jimd.12454.
  • Ziegler WH, Lüdiger S, Hassan F, Georgiadis ME, Swolana K, Khera A, Mertens A, Franke D, Wohlgemuth K, Dahmer-Heath M, König J, Dafinger C, Liebau MC, Cetiner M, 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 Mar 9;17(1):122. doi: 10.1186/s13023-022-02265-1.
  • Capone V, Persico N, Berrettini A, Decramer S, De Marco EA, De Palma D, Familiari A, Feitz W, Herthelius M, Kazlauskas V, Liebau M, Manzoni G, Maternik M, Mosiello G, Schanstra JP, Vande Walle J, Wuhl E, Ylinen E, Zurowska A, Schaefer F, and Montini G (2022). Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group. Nat Rev Urol19, 295-303. doi:10.1038/s41585-022-00563-8.
  • Kohl S, Avni FE, Boor P, Capone V, Clapp WL, De Palma D, Harris T, Heidet L, Hilger AC, Liapis H, Lilien M, Manzoni G, Montini G, Negrisolo S, Pierrat MJ, Raes A, Reutter H, Schreuder MF, Weber S, Winyard PJD, Woolf AS, Schaefer F, and Liebau MC (2022). Definition, diagnosis, and clinical management of non-obstructive kidney dysplasia: a consensus statement by the ERKNet working group on Kidney Malformations. Nephrol Dial Transplant. doi:10.1093/ndt/gfac207.
  • Burgmaier K, Kilian S, Arbeiter K, Atmis B, Büscher A, Derichs U, Dursun I, Duzova A, Eid LA, Galiano M, Gessner M, Gokce I, Haeffner K, Hooman N, Jankauskiene A, Körber F, Longo G, Massella L, Mekahli D, Miloševski-Lomić G, Nalcacioglu H, Rus R, Shroff R, Stabouli S, Weber LT, Wygoda S, Yilmaz A, Zachwieja K, Zagozdzon I, Dötsch J, Schaefer F, Liebau MC & the ARegPKD consortium. ”Early childhood height-adjusted total kidney volume as a risk marker of kidney survival in ARPKD”. Scientific Reports 2021 Nov 4;11(1):21677. doi: 10.1038/s41598-021-00523-z.
  • Burgmaier K, Brinker L, Erger F, Beck B, Benz M, 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 for the ARegPKD consortium. “Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease (ARPKD) and PKHD1 variants”. Kidney International 2021 Sep;100(3):650-659. doi: 10.1016/j.kint.2021.04.019.
  • Butt L, Unnersjo-Jess D, Hohne M, Hahnfeldt R, Reilly D, Rinschen MM, Plagmann I, Diefenhardt P, Brahler S, Brinkkotter PT, Brismar H, Blom H, Schermer B, and Benzing T (2022). Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular Disease. J Am Soc Nephrol33, 138-154. doi:10.1681/ASN.2020060858.
  • Butt L, Unnersjo-Jess D, Hohne M, Schermer B, Edwards A, and Benzing T (2021). A mathematical estimation of the physical forces driving podocyte detachment. Kidney Int100, 1054-1062. doi:10.1016/j.kint.2021.06.040.
  • Dafinger C, Benzing T, Dotsch J, Schermer B, and Liebau MC (2021). Targeted deletion of Ruvbl1 results in severe defects of epidermal development and perinatal mortality. Mol Cell Pediatr8, 1. doi:10.1186/s40348-021-00111-1.
  • 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.
                                      • He B, Chen P, Zambrano S, Dabaghie D, Hu Y, Moller-Hackbarth K, Unnersjo-Jess D, Korkut GG, Charrin E, Jeansson M, Bintanel-Morcillo M, Witasp A, Wennberg L, Wernerson A, Schermer B, Benzing T, Ernfors P, Betsholtz C, Lal M, Sandberg R, and Patrakka J (2021). Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes. Nat Commun12, 2141. doi:10.1038/s41467-021-22331-9.
                                      • Hoyer-Allo KJR, Spath MR, Hanssen R, Johnsen M, Brodesser S, Kaufmann K, Kiefer K, Koehler FC, Gobel H, Kubacki T, Grundmann F, Schermer B, Bruning J, Benzing T, Burst V, and Muller RU (2021). Modulation of Endocannabinoids by Caloric Restriction Is Conserved in Mice but Is Not Required for Protection from Acute Kidney Injury. Int J Mol Sci22. doi:10.3390/ijms22115485.
                                                                                                          • Koehler S, Odenthal J, Ludwig V, Jess DU, Hohne M, Jungst C, Grawe F, Helmstadter M, Janku JL, Bergmann C, Hoyer PF, Hagmann HHH, Walz G, Bloch W, Niessen C, Schermer B, Wodarz A, Denholm B, Benzing T, Iden S, and Brinkkoetter PT (2021). Scaffold polarity proteins Par3A and Par3B share redundant functions while Par3B acts independent of atypical protein kinase C/Par6 in podocytes to maintain the kidney filtration barrier. Kidney Int. doi:10.1016/j.kint.2021.11.030.
                                                                                                                                                    • Mangold N, Pippin J, Unnersjoe-Jess D, Koehler S, Shankland S, Brahler S, Schermer B, Benzing T, Brinkkoetter PT, and Hagmann H (2021). The Atypical Cyclin-Dependent Kinase 5 (Cdk5) Guards Podocytes from Apoptosis in Glomerular Disease While Being Dispensable for Podocyte Development. Cells10. doi:10.3390/cells10092464.
                                                                                                                                                                                                                                  • 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.
                                                                                                                                                                                                                                  • 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.
                                                                                                                                                                                                                                  • Gimpel C, Liebau MC, Schaefer F. „Systematic review on outcomes used in clinical research on autosomal recessive polycystic kidney disease—are patient-centered outcomes our blind spot?“ PediatricNephrology, 2021 Dec;36(12):3841-3851. doi: 10.1007/s00467-021-05192-8. 
                                                                                                                                                                                                                                  • Haumann S, Müller RU, Liebau MC. „Metabolic changes in polycystic kidney disease as a potential target for systemic treatment“; International Journal of Molecular Sciences. 2020, 21(17), 6093; doi.org/10.3390/ijms21176093
                                                                                                                                                                                                                                  • Janssens P, Jouret F, Bammens B, Liebau MC, Schaefer F, Dandurand A, Perrone RD, Müller RU, Pao CS, Mekahli D. „Implications of early diagnosis of autosomal dominant polycystic kidney disease: A post hoc analysis of the TEMPO 3:4 trial“ Scientific Reports, 2020 Mar 9;10(1):4294. doi: 10.1038/s41598-020-61303-9
                                                                                                                                                                                                                                  • Kaczmarek AT, Bender D, Gehling T, Kohl JB, Daimaguler HS, Santamaria-Araujo JA, Liebau MC, Koy A, Cirak S, and Schwarz G (2021). A defect in molybdenum cofactor binding causes an attenuated form of sulfite oxidase deficiency. J Inherit Metab Dis. doi:10.1002/jimd.12454.
                                                                                                                                                                                                                                                                                                                                                                                    • Kohl S, Habbig S, Weber LT, and Liebau MC (2021). Molecular causes of congenital anomalies of the kidney and urinary tract (CAKUT). Mol Cell Pediatr8, 2. doi:10.1186/s40348-021-00112-0.
                                                                                                                                                                                                                                                                                                                                                                                    • Liebau MC (2021). Early clinical management of autosomal recessive polycystic kidney disease. Pediatr Nephrol36, 3561-3570. doi:10.1007/s00467-021-04970-8.
                                                                                                                                                                                                                                                                                                                                                                                    • Liebau MC, and Mekahli D (2021). Translational research approaches to study pediatric polycystic kidney disease. Mol Cell Pediatr8, 20. doi:10.1186/s40348-021-00131-x.
                                                                                                                                                                                                                                                                                                                                                                                    • Unnersjo-Jess D, Butt L, Hohne M, Witasp A, Kuhne L, Hoyer PF, Patrakka J, Brinkkotter PT, Wernerson A, Schermer B, Benzing T, Scott L, Brismar H, and Blom H (2021). A Fast and Simple Clearing and Swelling Protocol for 3D In-Situ Imaging of the Kidney across Scales. Kidney Int. 99, 1010-1020.
                                                                                                                                                                                                                                                                                                                                                                                    • Binz-Lotter J, Jungst C, Rinschen MM, Koehler S, Zentis P, Schauss A, Schermer B, Benzing T, and Hackl MJ (2020). Injured Podocytes Are Sensitized to Angiotensin II-Induced Calcium Signaling. J Am Soc Nephrol 31, 532-42.
                                                                                                                                                                                                                                                                                                                                                                                    • Braun F, Rinschen M, Buchner D, Bohl K, Plagmann I, Bachurski D, Richard Spath M, Antczak P, Gobel H, Klein C, Lackmann JW, Kretz O, Puelles VG, Wahba R, Hallek M, Schermer B, Benzing T, Huber TB, Beyer A, Stippel D, Kurschat CE, and Muller RU (2020). The proteomic landscape of small urinary extracellular vesicles during kidney transplantation. Journal of extracellular vesicles 10, e12026.
                                                                                                                                                                                                                                                                                                                                                                                    • 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.
                                                                                                                                                                                                                                                                                                                                                                                    • Dafinger C, Mandel AM, Braun A, Göbel H, Burgmaier K, Massella L, Mastrangelo A, Dötsch J, Benzing T, Weimbs T, Schermer B, Liebau MC. „The carboxy-terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC-activation“; Journal of Cellular and Molecular Medicine, 2020 Dec;24(24):14633-14638. doi: 10.1111/jcmm.16014.
                                                                                                                                                                                                                                                                                                                                                                                    • Gimpel C, Liebau MC, Schaefer F. „Systematic review on outcomes used in clinical research on autosomal recessive polycystic kidney disease—are patient-centered outcomes our blind spot?“ Pediatric Nephrology, 2020 Dec;36(12):3841-3851. doi: 10.1007/s00467-021-05192-8.  
                                                                                                                                                                                                                                                                                                                                                                                    • Haumann S, Müller RU, Liebau MC. „Metabolic changes in polycystic kidney disease as a potential target for systemic treatment“; International Journal of Molecular Sciences. 2020, 21(17), 6093; doi.org/10.3390/ijms21176093
                                                                                                                                                                                                                                                                                                                                                                                    • Janssens P, Jouret F, Bammens B, Liebau MC, Schaefer F, Dandurand A, Perrone RD, Müller RU, Pao CS, Mekahli D. „Implications of early diagnosis of autosomal dominant polycystic kidney disease: A post hoc analysis of the TEMPO 3:4 trial“ Scientific Reports, 2020 Mar 9;10(1):4294. doi: 10.1038/s41598-020-61303-9
                                                                                                                                                                                                                                                                                                                                                                                    • 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 Nephrol 31, 716-30.
                                                                                                                                                                                                                                                                                                                                                                                    • 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.
                                                                                                                                                                                                                                                                                                                                                                                    • Matin M, Morgelin M, Stetefeld J, Schermer B, Brinkkoetter PT, Benzing T, Koch M, and Hagmann H (2020). Affinity-Enhanced Multimeric VEGF (Vascular Endothelial Growth Factor) and PlGF (Placental Growth Factor) Variants for Specific Adsorption of sFlt-1 to Restore Angiogenic Balance in Preeclampsia. Hypertension 76, 1176-84.
                                                                                                                                                                                                                                                                                                                                                                                    • Schermer B, Fabretti F, Damagnez M, Di Cristanziano V, Heger E, Arjune S, Tanner NA, Imhof T, Koch M, Ladha A, Joung J, Gootenberg JS, Abudayyeh OO, Burst V, Zhang F, Klein F, Benzing T, and Muller RU (2020). Rapid SARS-CoV-2 testing in primary material based on a novel multiplex RT-LAMP assay. PloS one 15, e0238612.
                                                                                                                                                                                                                                                                                                                                                                                    • Unnersjo-Jess D, Butt L, Hohne M, Witasp A, Kuhne L, Hoyer PF, Patrakka J, Brinkkotter PT, Wernerson A, Schermer B, Benzing T, Scott L, Brismar H, and Blom H (2020). A Fast and Simple Clearing and Swelling Protocol for 3D In-Situ Imaging of the Kidney across Scales. Kidney Int 10.1016/j.kint.2020.10.039.
                                                                                                                                                                                                                                                                                                                                                                                    • Muller RU, and Schermer B (2020). Hippo signaling-a central player in cystic kidney disease? Pediatr Nephrol35, 1143-1152. doi:10.1007/s00467-019-04299-3.
                                                                                                                                                                                                                                                                                                                                                                                    • 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.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      • Nusken E, Fink G, Lechner F, Voggel J, Wohlfarth M, Sprenger L, Mehdiani N, Weber LT, Liebau MC, Brachvogel B, Dotsch J, and Nusken KD (2020). Altered molecular signatures during kidney development after intrauterine growth restriction of different origins. J Mol Med (Berl)98, 395-407. doi:10.1007/s00109-020-01875-1.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Wicher D, Grenda R, Teisseyre M, Szymczak M, Halat-Wolska P, Jurkiewicz D, Liebau MC, Ciara E, Rydzanicz M, Kosinska J, Chrzanowska K, and Jankowska I (2020). Occurrence of Portal Hypertension and Its Clinical Course in Patients With Molecularly Confirmed Autosomal Recessive Polycystic Kidney Disease (ARPKD). Front Pediatr8, 591379. doi:10.3389/fped.2020.591379.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              • Strubl S, Torres JA, Spindt AK, Pellegrini H, Liebau MC, and Weimbs T (2020). STAT signaling in polycystic kidney disease. Cell Signal72, 109639. doi:10.1016/j.cellsig.2020.109639.
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Prof. Dr. Bernhard Schermer CMMC Cologne
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Prof. Dr. Bernhard Schermer

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Clinic II of Internal Medicine

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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Publications - Bernhard Schermer

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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              PD Dr. Max C Liebau CMMC Cologne
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              PD Dr. Max C Liebau

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Clinic and Polyclinic for Pediatric and Adolescent Medicine

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              CMMC - Co-PI - C 14

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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Clinic and Polyclinic for Pediatric and Adolescent Medicine

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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              50937 Cologne

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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Publications - Max C Liebau

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