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 Forschungsbericht für das Jahr 2017

Institut für Molekulare Medizin und Zellforschung (IMMZ)

Zentrum für Biochemie und Molekulare Zellforschung (ZBMZ)

Stefan-Meier-Str. 17
79104 Freiburg i. Br.
Tel: +49-761-203-9600/9601 Fax: +49-761-203-9602
Email christoph.peters@mol-med.uni-freiburg.de
http://www.mol-med.uni-freiburg.de


Wissenschaftliche Mitarbeiterinnen und Mitarbeiter

  • Prof. Dr. Christoph Peters, Institutsleiter
  • Dr. Martin Biniossek, Gruppenleiter
  • Prof. Dr. Dr. h.c. Christoph Borner, Gruppenleiter
  • Dr. Dr. Melanie Börries, Gruppenleiterin
  • Dr. Tilman Brummer, Gruppenleiter
  • Prof. Dr. Andreas Hecht, Gruppenleiter
  • Dr. Ulrich Maurer, Gruppenleiter
  • Prof. Dr. Thomas Reinheckel, Gruppenleiter
  • Dr. Oliver Schilling, Gruppenleiter
  • Dr. Geoffroy Andrieux, Wissenschaftlicher Mitarbeiter
  • Dr. Ulrike Burk, Wissenschaftliche Mitarbeiterin
  • Dr. Lars Nilse, Wissenschaftlicher Mitarbeiter
  • Dr. Priska Brauns-Schubert, Postdoc (m/w)
  • Dr. Chia-Yi Chen, Postdoc (m/w)
  • Dr. Alejandro Gomez-Aulí, Postdoc (m/w)
  • Dr. Sebastian Halbach, Postdoc (m/w)
  • Dr. Florian Haun, Postdoc (m/w)
  • Dr. Ricarda Herr, Postdoc (m/w)
  • Dr. Ursula Kern, Wissenschaftlicher Mitarbeiter (m/w)
  • Dr. Maria Koczorowska, Wissenschaftliche Mitarbeiterin
  • Dr. Ella Levit-Zerdoun, Postdoc
  • Dr. Julia Mitschke, Postdoc
  • Dr. Simon Neumann, Postdoc
  • Dr. Lukas Peintner, Postdoc (m/w)
  • Dr. Agnese Petrera, Postdoc
  • Dr. Florian Schubert
  • Dr. Florian Weinberg, Postdoc
Einträge in der Rubrik "Who is Who"

Forschungsschwerpunkte

  • Funktion der Bcl-2 Familie und Identifikation von neuen Komponenten der Caspase-unabhängigen Zelltodwege
  • In vivo Funktionen von Proteasen
  • Massenspektrometrie
  • Modulation von Signaltransduktionsprozessen in der Embryonalentwicklung und Tumorigenese
  • Protease Degradomik
  • Signaltransduktion in Tumorentwicklung und Medikamentenresistenz
  • Signaltransduktion in Zelltod und -überleben
  • Systembiologie von zellulärer Mikroumgebung
  • Tumorinvasion und Metastasierung

Finanzierung

  • siehe: www.mol-med.uni-freiburg.de

Wissenschaftliche Publikationen

Originalarbeiten in wissenschaftlichen Fachzeitschriften:
  • Adlung L, Kar S, Wagner MC, She B, Chakraborty S, Bao J, Lattermann S, Boerries M, Busch H, Wuchter P, Ho AD, Timmer J, Schilling M, Hofer T, Klingmuller U: Protein abundance of AKT and ERK pathway components governs cell type-specific regulation of proliferation. Mol Syst Biol, 2017; 13 (1): 904-904.
  • Aghdassi AA, John DS, Sendler M, Weiss FU, Reinheckel T, Mayerle J, Lerch MM: Cathepsin D regulates cathepsin B activation and disease severity predominantly in inflammatory cells during experimental pancreatitis. J Biol Chem, 2017. : http://dx.doi.org/10.1074/jbc.M117.814772 (in Druck)
  • Allan ERO, Campden RI, Ewanchuk BW, Tailor P, Balce DR, McKenna NT, Greene CJ, Warren AL, Reinheckel T, Yates RM: A role for cathepsin Z in neuroinflammation provides mechanistic support for an epigenetic risk factor in multiple sclerosis. J Neuroinflamm, 2017; 14 (1) (online): 103-103. : http://dx.doi.org/10.1186/s12974-017-0874-x
  • Andrlova H, Mastroianni J, Madl J, Kern JS, Melchinger W, Dierbach H, Wernet F, Follo M, Technau-Hafsi K, Has C, Rao Mittapalli V, Idzko M, Herr R, Brummer T, Ungefroren H, Busch H, Boerries M, Narr A, Ihorst G, Vennin C, Schmitt-Graeff A, Minguet S, Timpson P, Duyster J, Meiss F, Romer W, Zeiser R: Biglycan expression in the melanoma microenvironment promotes invasiveness via increased tissue stiffness inducing integrin-beta1 expression. Oncotarget, 2017; 8 (26): 42901-42916. : http://dx.doi.org/10.18632/oncotarget.17160
  • Barrow TM *, Klett H *, Toth R, Bohm J, Gigic B, Habermann N, Scherer D, Schrotz-King P, Skender S, Abbenhardt-Martin C, Zielske L, Schneider M, Ulrich A, Schirmacher P, Herpel E, Brenner H, Busch H, Boerries M, Ulrich CM *, Michels KB *: Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study. J Pathol, 2017; 243 (3): 366-375. : http://dx.doi.org/10.1002/path.4955
  • Cabrera AC, Melo E, Roth D, Topp A, Delobel F, Stucki C, Chen CY, Jakob P, Banfai B, Dunkley T, Schilling O, Huber S, Iacone R, Petrone P: HtrA1 activation is driven by an allosteric mechanism of inter-monomer communication. Sci Rep-uk, 2017; 7 (1): 14804-14804. : http://dx.doi.org/10.1038/s41598-017-14208-z
  • Chen CY, Mayer B, Schilling O: Profiling of Protease Cleavage Sites by Proteome-Derived Peptide Libraries and Quantitative Proteomics. Methods Mol Biol, 2017; 1574 (online): 197-204. : http://dx.doi.org/10.1007/978-1-4939-6850-3_14
  • Diedrich B *, Rigbolt KT *, Roring M, Herr R, Kaeser-Pebernard S, Gretzmeier C, Murphy RF, Brummer T *, Dengjel J *: Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition. Embo J, 2017; 36 (5): 646-663. : http://dx.doi.org/10.15252/embj.201694732
  • Drendel V, Heckelmann B, Chen CY, Weisser J, Espadas G, Schell C, Sabido E, Werner M, Jilg CA, Schilling O: Proteome profiling of clear cell renal cell carcinoma in von Hippel-Lindau patients highlights upregulation of Xaa-Pro aminopeptidase-1, an Oncotarget, 2017; 8 (59): 100066-100078. : http://dx.doi.org/10.18632/oncotarget.21929
  • Enderle-Ammour K, Bader M, Ahrens TD, Franke K, Timme S, Csanadi A, Hoeppner J, Kulemann B, Maurer J, Reiss P, Schilling O, Keck T, Brabletz T, Stickeler E, Werner M, Wellner UF, Bronsert P: Form follows function: Morphological and immunohistological insights into epithelial-mesenchymal transition characteristics of tumor buds. Tumor Biol, 2017; 39 (5) (online): 1010428317705501-1010428317705501. : http://dx.doi.org/10.1177/1010428317705501
  • Fichter CD, Przypadlo CM, Buck A, Herbener N, Riedel B, Schafer L, Nakagawa H, Walch A, Reinheckel T, Werner M, Lassmann S: A new model system identifies epidermal growth factor receptor-human epidermal growth factor receptor 2 (HER2) and HER2-human epidermal growth factor receptor 3 heterodimers as potent inducers of oesophageal epithelial cell invasion. J Pathol, 2017; 243 (4): 481-495. : http://dx.doi.org/10.1002/path.4987
  • Föll MC, Fahrner M, Gretzmeier C, Thoma K, Biniossek ML, Kiritsi D, Meiss F, Schilling O, Nyström A, Kern JS: Identification of tissue damage, extracellular matrix remodeling and bacterial challenge as common mechanisms associated with high-risk cutaneous squamous cell carcinomas. Matrix Biol, 2017. : http://dx.doi.org/10.1016/j.matbio.2017.11.004 (in Druck)
  • Fuellgraf H, Schilling O, Lai ZW, Kulemann B, Timme S, Makowiec F, Shahinian JH, Hoeppner J, Werner M, Hopt UT, Wellner UF, Bronsert P: The Prognostic Impact of the Carcinoembryonic Antigen in Ampullary Cancer - A Retrospective Single Center Study. J Cancer, 2017; 8 (4): 657-664. : http://dx.doi.org/10.7150/jca.16200
  • Hinderer M, Boerries M, Haller F, Wagner S, Sollfrank S, Acker T, Prokosch HU, Christoph J: Supporting Molecular Tumor Boards in Molecular-Guided Decision-Making - The Current Status of Five German University Hospitals. Stud Health Technol Inform, 2017; 236: 48-54.
  • Jagle S, Busch H, Freihen V, Beyes S, Schrempp M, Boerries M, Hecht A: SNAIL1-mediated downregulation of FOXA proteins facilitates the inactivation of transcriptional enhancer elements at key epithelial genes in colorectal cancer cells. Plos Genet, 2017; 13 (11) (online): e1007109-e1007109. : http://dx.doi.org/10.1371/journal.pgen.1007109
  • Jagle S, Dertmann A, Schrempp M, Hecht A: ZEB1 is neither sufficient nor required for epithelial-mesenchymal transition in LS174T colorectal cancer cells. Biochem Bioph Res Co, 2017; 482 (4): 1226-1232. : http://dx.doi.org/10.1016/j.bbrc.2016.12.017
  • Koczorowska MM, Friedemann C, Geiger K, Follo M, Biniossek ML, Schilling O: Differential effect of TGFbeta on the proteome of cancer associated fibroblasts and cancer epithelial cells in a co-culture approach - a short report. Cell Oncol, 2017; 40 (6): 639-650. : http://dx.doi.org/10.1007/s13402-017-0344-6
  • Krebs AM, Mitschke J, Losada ML, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, Brunton VG, Pilarsky C, Winkler TH, Brabletz S, Stemmler MP, Brabletz T: The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol, 2017; 19 (5): 518-529. : http://dx.doi.org/10.1038/ncb3513
  • Lai ZW, Schilling O: Identification of Protease Cleavage Sites by Charge-Based Enrichment of Protein N-Termini. Methods Mol Biol, 2017; 1579: 199-207. : http://dx.doi.org/10.1007/978-1-4939-6863-3_10
  • Lai ZW, Schilling O: System-Wide Profiling of Protein Amino Termini from Formalin-Fixed, Paraffin-Embedded Tissue Specimens for the Identification of Novel Substrates. Methods Mol Biol, 2017; 1574 (online): 105-114. : http://dx.doi.org/10.1007/978-1-4939-6850-3_8
  • Lang S, Busch H, Boerries M, Brummer T, Timme S, Lassmann S, Aktories K, Schmidt G: Specific role of RhoC in tumor invasion and metastasis. Oncotarget, 2017; 8 (50) (online): 87364-87378. : http://dx.doi.org/10.18632/oncotarget.20957
  • Lipka DB, Witte T, Toth R, Yang J, Wiesenfarth M, Nollke P, Fischer A, Brocks D, Gu Z, Park J, Strahm B, Wlodarski M, Yoshimi A, Claus R, Lubbert M, Busch H, Boerries M, Hartmann M, Schonung M, Kilik U, Langstein J, Wierzbinska JA, Pabst C, Garg S, Catala A, De Moerloose B, Dworzak M, Hasle H, Locatelli F, Masetti R, Schmugge M, Smith O, Stary J, Ussowicz M, van den Heuvel-Eibrink MM, Assenov Y, Schlesner M, Niemeyer C, Flotho C, Plass C: RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nat Commun, 2017; 8 (1) (online): 2126-2126. : http://dx.doi.org/10.1038/s41467-017-02177-w
  • Melo E, Oertle P, Trepp C, Meistermann H, Burgoyne T, Sborgi L, Cabrera AC, Chen CY, Hoflack JC, Kam-Thong T, Schmucki R, Badi L, Flint N, Ghiani ZE, Delobel F, Stucki C, Gromo G, Einhaus A, Hornsperger B, Golling S, Siebourg-Polster J, Gerber F, Bohrmann B, Futter C, Dunkley T, Hiller S, Schilling O, Enzmann V, Fauser S, Plodinec M, Iacone R: HtrA1 Mediated Intracellular Effects on Tubulin Using a Polarized RPE Disease Model. EBioMedicine, 2017. : http://dx.doi.org/10.1016/j.ebiom.2017.12.011 (in Druck)
  • Mengwasser J, Babes L, Cordes S, Mertlitz S, Riesner K, Shi Y, McGearey A, Kalupa M, Reinheckel T, Penack O: Cathepsin E Deficiency Ameliorates Graft-versus-Host Disease and Modifies Dendritic Cell Motility. Front Immunol, 2017; 8 (online): 203-203. : http://dx.doi.org/10.3389/fimmu.2017.00203
  • Metzger E, Stepputtis SS, Strietz J, Preca BT, Urban S, Willmann D, Allen A, Zenk F, Iovino N, Bronsert P, Proske A, Follo M, Boerries M, Stickeler E, Xu J, Wallace MB, Stafford JA, Kanouni T, Maurer J, Schule R: KDM4 Inhibition Targets Breast Cancer Stem-like Cells. Cancer Res, 2017; 77 (21): 5900-5912. : http://dx.doi.org/10.1158/0008-5472.CAN-17-1754
  • Naeem AS, Tommasi C, Cole C, Brown SJ, Zhu Y, Way B, Willis Owen SA, Moffatt M, Cookson WO, Harper JI, Di WL, Brown SJ, Reinheckel T, O'Shaughnessy RF: A mechanistic target of rapamycin complex 1/2 (mTORC1)/V-Akt murine thymoma viral oncogene homolog 1 (AKT1)/cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in patients with atopic dermatitis. J Allergy Clin Immun, 2017; 139 (4): 1228-1241. : http://dx.doi.org/10.1016/j.jaci.2016.09.052
  • Nkuipou-Kenfack E, Schanstra JP, Bajwa S, Pejchinovski M, Vinel C, Dray C, Valet P, Bascands JL, Vlahou A, Koeck T, Borries M, Busch H, Bechtel-Walz W, Huber TB, Rudolph KL, Pich A, Mischak H, Zurbig P: The use of urinary proteomics in the assessment of suitability of mouse models for ageing. Plos One, 2017; 12 (2) (online): e0166875. : http://dx.doi.org/10.1371/journal.pone.0166875
  • Oortveld MAW, van Vlijmen-Willems IMJJ, Kersten FFJ, Cheng T, Verdoes M, van Erp PEJ, Verbeek S, Reinheckel T, Hendriks WJAJ, Schalkwijk J, Zeeuwen PLJM: Cathepsin B as a potential cystatin M/E target in the mouse hair follicle. Faseb J, 2017; 31 (10): 4286-4294. : http://dx.doi.org/10.1096/fj.201700267R
  • Paireder M, Tholen S, Porodko A, Biniossek ML, Mayer B, Novinec M, Schilling O, Mach L: The papain-like cysteine proteinases NbCysP6 and NbCysP7 are highly processive enzymes with substrate specificities complementary to Nicotiana benthamiana cathepsin B. Bba-proteins Proteom, 2017; 1865 (4): 444-452. : http://dx.doi.org/10.1016/j.bbapap.2017.02.007
  • Panayotopoulou EG, Muller AK, Borries M, Busch H, Hu G, Lev S: Targeting of apoptotic pathways by SMAC or BH3 mimetics distinctly sensitizes paclitaxel-resistant triple negative breast cancer cells. Oncotarget, 2017; 8 (28): 45088-45104. : http://dx.doi.org/10.18632/oncotarget.15125
  • Pastor VB, Sahoo S, Boklan J, Schwabe GC, Saribeyoglu E, Strahm B, Lebrecht D, Voss M, Bryceson YT, Erlacher M, Ehninger G, Niewisch M, Schlegelberger B, Baumann I, Achermann JC, Shimamura A, Hochrein J, Tedgard U, Nilsson L, Hasle H, Boerries M, Busch H, Niemeyer CM, Wlodarski MW: Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. Haematologica, 2017. : http://dx.doi.org/10.3324/haematol.2017.180778 (in Druck)
  • Pazzagli C, He Y, Busch H, Esser P, Kiritsi D, Gache Y, Bruckner-Tuderman L, Boerries M, Has C: Absence of the Integrin alpha3 Subunit Induces an Activated Phenotype in Human Keratinocytes. J Invest Dermatol, 2017; 137 (6): 1387-1391. : http://dx.doi.org/10.1016/j.jid.2017.01.018
  • Rogg M, Yasuda-Yamahara M, Abed A, Dinse P, Helmstadter M, Conzelmann AC, Frimmel J, Sellung D, Biniossek ML, Kretz O, Grahammer F, Schilling O, Huber TB, Schell C: The WD40-domain containing protein CORO2B is specifically enriched in glomerular podocytes and regulates the ventral actin cytoskeleton. Sci Rep-uk, 2017; 7 (1) (online): 15910-15910. : http://dx.doi.org/10.1038/s41598-017-15844-1
  • Selt F, Hohloch J, Hielscher T, Sahm F, Capper D, Korshunov A, Usta D, Brabetz S, Ridinger J, Ecker J, Oehme I, Gronych J, Marquardt V, Pauck D, Bachli H, Stiles CD, von Deimling A, Remke M, Schuhmann MU, Pfister SM, Brummer T, Jones DT, Witt O, Milde T: Establishment and application of a novel patient-derived KIAA1549:BRAF-driven pediatric pilocytic astrocytoma model for preclinical drug testing. Oncotarget, 2017; 8 (7): 11460-11479. : http://dx.doi.org/10.18632/oncotarget.14004
  • Shahinian JH, Mayer B, Tholen S, Brehm K, Biniossek ML, Fullgraf H, Kiefer S, Heizmann U, Heilmann C, Ruter F, Grapow M, Reuthebuch OT, Eckstein F, Beyersdorf F, Schilling O, Siepe M: Proteomics highlights decrease of matricellular proteins in left ventricular assist device therapydagger. Eur J Cardio-thorac, 2017; 51 (6): 1063-1071. : http://dx.doi.org/10.1093/ejcts/ezx023
  • Sigloch FC, Tholen M, Gomez-Auli A, Biniossek ML, Reinheckel T, Schilling O: Proteomic analysis of lung metastases in a murine breast cancer model reveals divergent influence of CTSB and CTSL overexpression. J Cancer, 2017; 8 (19): 4065-4074. : http://dx.doi.org/10.7150/jca.21401
  • Silva-Vilches C, Pletinckx K, Lohnert M, Pavlovic V, Ashour D, John V, Vendelova E, Kneitz S, Zhou J, Chen R, Reinheckel T, Mueller TD, Bodem J, Lutz MB: Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion. Plos One, 2017; 12 (7) (online): e0178114-e0178114. : http://dx.doi.org/10.1371/journal.pone.0178114
  • Singh PK, Roukounakis A, Frank DO, Kirschnek S, Das KK, Neumann S, Madl J, Romer W, Zorzin C, Borner C, Haimovici A, Garcia-Saez A, Weber A, Hacker G: Dynein light chain 1 induces assembly of large Bim complexes on mitochondria that stabilize Mcl-1 and regulate apoptosis. Gene Dev, 2017; 31 (17): 1754-1769. : http://dx.doi.org/10.1101/gad.302497.117
  • Stickel N, Hanke K, Marschner D, Prinz G, Kohler M, Melchinger W, Pfeifer D, Schmitt-Graeff A, Brummer T, Heine A, Brossart P, Wolf D, von Bubnoff N, Finke J, Duyster J, Ferrara J, Salzer U, Zeiser R: MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation. Leukemia, 2017; 31 (12): 2732-2741. : http://dx.doi.org/10.1038/leu.2017.137
  • Strotbek M, Schmid S, Sanchez-Gonzalez I, Boerries M, Busch H, Olayioye MA: miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer. Int J Cancer, 2017; 140 (10): 2310-2320. : http://dx.doi.org/10.1002/ijc.30661
  • van der Meer LT, Terry SY, van Ingen Schenau DS, Andree KC, Franssen GM, Roeleveld DM, Metselaar JM, Reinheckel T, Hoogerbrugge PM, Boerman OC, van Leeuwen FN: In Vivo Imaging of Antileukemic Drug Asparaginase Reveals a Rapid Macrophage-Mediated Clearance from the Bone Marrow. J Nucl Med, 2017; 58 (2): 214-220. : http://dx.doi.org/10.2967/jnumed.116.177741
  • Weinberg F, Reischmann N, Fauth L, Taromi S, Mastroianni J, Kohler M, Halbach S, Becker AC, Deng N, Schmitz T, Uhl FM, Herbener N, Riedel B, Beier F, Swarbrick A, Lassmann S, Dengjel J, Zeiser R, Brummer T: The Atypical Kinase RIOK1 Promotes Tumor Growth and Invasive Behavior. EBioMedicine, 2017; 20 (online): 79-97. : http://dx.doi.org/10.1016/j.ebiom.2017.04.015
  • Zhou X, Paushter DH, Feng T, Sun L, Reinheckel T, Hu F: Lysosomal processing of progranulin. Mol Neurodegener, 2017; 12 (1) (online): 62-62. : http://dx.doi.org/10.1186/s13024-017-0205-9
Reviews/Übersichtsartikel in wissenschaftlichen Fachzeitschriften:
  • Fuchs JE, Schilling O, Liedl KR: Determinants of Macromolecular Specificity from Proteomics-Derived Peptide Substrate Data. Curr Protein Pept Sc, 2017; 18 (9): 905-913. : http://dx.doi.org/10.2174/1389203717666160724211231
  • Hettmer S, Andrieux G, Hochrein J, Kurz P, Rossler J, Lassmann S, Werner M, von Bubnoff N, Peters C, Koscielniak E, Sparber-Sauer M, Niemeyer C, Mentzel T, Busch H, Boerries M: Epithelioid hemangioendotheliomas of the liver and lung in children and adolescents. Pediatr Blood Cancer, 2017; 64 (12) (online). : http://dx.doi.org/10.1002/pbc.26675
  • Ketterer S, Gomez-Auli A, Hillebrand LE, Petrera A, Ketscher A, Reinheckel T: Inherited diseases caused by mutations in cathepsin protease genes. Febs J, 2017; 284 (10): 1437-1454. : http://dx.doi.org/10.1111/febs.13980
  • Peintner L, Borner C: Role of apoptosis in the development of autosomal dominant polycystic kidney disease (ADPKD). Cell Tissue Res, 2017; 369 (1): 27-39. : http://dx.doi.org/10.1007/s00441-017-2628-6
  • Pfeuffer J, Sachsenberg T, Alka O, Walzer M, Fillbrunn A, Nilse L, Schilling O, Reinert K, Kohlbacher O: OpenMS - A platform for reproducible analysis of mass spectrometry data. J Biotechnol, 2017; 261: 142-148. : http://dx.doi.org/10.1016/j.jbiotec.2017.05.016
  • Schlicher L, Brauns-Schubert P, Schubert F, Maurer U: SPATA2: more than a missing link. Cell Death Differ, 2017; 24 (7): 1142-1147. : http://dx.doi.org/10.1038/cdd.2017.26
  • Sulaimanov N, Klose M, Busch H, Boerries M: Understanding the mTOR signaling pathway via mathematical modeling. Wires Syst Biol Med, 2017; 9 (4) (online). : http://dx.doi.org/10.1002/wsbm.1379
Sonstige Publikationen:

Besondere wissenschaftliche Aktivitäten

Abschlussarbeiten