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Workgroup Prof. Dr. Dr. Christoph Schell

MatriPath - Lab (Laboratory for Experimental Nephropathology and Urological Malignancies)

Welcome to the laboratory of Prof. Dr. Dr. Christoph Schell.

The Schell laboratory is interested in the role and nature of cell-matrix interactions contributing to the whole spectrum of genetic kidney disease as well as urological malignancies.

Figure 1: Scanning electron microscopy (SEM) image of a mouse glomerulus depicting the intricate morphology of podocytes Figure 1: Scanning electron microscopy (SEM) image of a mouse glomerulus depicting the intricate morphology of podocytes

Experimental Nephropathology

The glomerulus presents a multi-cellular filtration unit and the complex spectrum of glomerular diseases is a major factor in the development of chronic kidney disease. We are highly interested in deciphering the intricate interplay of glomerular epithelial cells (podocytes), endothelial and mesangial cells as well as the glomerular basement membrane in providing the integrity of the filtration barrier. By employing a wide set of in vitro and in vivo methods we are investigating a) podocyte biology, b) cell-matrix interactions at the glomerular basement membrane and c) impact of cell-matrix interaction contributing to chronic and cystic kidney disease.

Figure 2: Image segmentation and digital pathology to extract quantitative morphometric parameters for further definition of the tumor microenvironment

Urological Malignancies

Renal cell carcinoma and bladder cancer are highly relevant urological malignancies. Our group is focusing on the role of cell-matrix interactions as well as the composition of the matrisome. Employing in vitro, in vivo and in situ technologies, we are aiming to dissect the instructive role for the tumor microenvironment and metastasis.

Figure 3: Confocal immunofluorescence imaging showing distribution of collagen and fibronectin networks within cellular derived matrices

Key Techniques

  • Complex genetic in vivo models
  • CRISPR/Cas9 genome editing
  • Primary and 3D-organoid cell culture
  • Multiplex imaging
  • Molecular biology
  • Advanced tissue imaging

Christoph Schell (MD/PhD – Principal Investigator)

Manuel Rogg (MD – Postdoctoral fellow)

Annika Merz (M.Sc., PhD candidate)

Max Wess (M.Sc., PhD candidate)

Grigor Andreev (Physician Scientist)

Viviana Barrera Penagos (Physician Scientist)

Michelle Shabani (MD, Physician Scientist)

Luise Bergmann (MD, Physician Scientist)

Elisabeth Schygulla (MD, Physician Scientist)

Marc-Antoine Calba (Physician Scientist)

Lisa Weißer (cand. med.)

Charlotte Kark (cand. med.)

Constance Gueib-Picard (cand. med. dent.)

Marlene Stilger (M.Sc.)

Alena Sammarco (MTA)

Katja Gräwe (VMTA)

Dr. Jasmin Maier

Markus Ehle (Medical Student)

Mira Ziob (Medical Student)

Prof. Dr. Dr. Christoph Schell - UrKidPath-Lab

Institute of Surgical Pathology

Breisacher Str. 115a

University Medical Center Freiburg

Germany

christoph.schell@uniklinik-freiburg.de

Funding

The Schell laboratory is supported by the German Research Council (Deutsche Forschungsgemeinschaft, DFG) and the Wilhelm Sander-Stiftung. We are also part of the CRC NephGen (SFB 1453), CRC Impath (SFB 1160) and the Clinical Research Unit (KFO 329 – Disease pathways in podocyte injury).

2024

  • Cosenza-Contreras M, Seredynska A, Vogele D, Pinter N, Brombacher E, Cueto RF, Dinh TJ, Bernhard P, Rogg M, Liu J, Willems P, Stael S, Huesgen PF, Kuehn EW, Kreutz C, Schell C, Schilling O. TermineR: Extracting information on endogenous proteolytic processing from shotgun proteomics data. Proteomics. 2024;24(19):e2300491. DOI: 10.1002/pmic.202300491.

  • Arnold F, Kupferschmid L, Weissenborn P, Heldmann L, Hummel JF, Zareba P, Sagar, Rogg M, Schell C, Tanriver Y. Tissue-resident memory T cells break tolerance to renal autoantigens and orchestrate immune-mediated nephritis. Cellular & molecular immunology. 2024;21(9):1066-81. DOI: 10.1038/s41423-024-01197-z.

  • Moeed A, Thilmany N, Beck F, Puthussery BK, Ortmann N, Haimovici A, Badr MT, Haghighi EB, Boerries M, Öllinger R, Rad R, Kirschnek S, Gentle IE, Donakonda S, Petric PP, Hummel JF, Pfaffendorf E, Zanetta P, Schell C, Schwemmle M, Weber A, Häcker G. The Caspase-Activated DNase drives inflammation and contributes to defense against viral infection. Cell death and differentiation. 2024;31(7):924-37. DOI: 10.1038/s41418-024-01320-7.

  • Kögl T, Chang HF, Staniek J, Chiang SCC, Thoulass G, Lao J, Weißert K, Dettmer-Monaco V, Geiger K, Manna PT, Beziat V, Momenilandi M, Tu SM, Keppler SJ, Pattu V, Wolf P, Kupferschmid L, Tholen S, Covill LE, Ebert K, Straub T, Groß M, Gather R, Engel H, Salzer U, Schell C, Maier S, Lehmberg K, Cornu TI, Pircher H, Shahrooei M, Parvaneh N, Elling R, Rizzi M, Bryceson YT, Ehl S, Aichele P, Ammann S. Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect. The Journal of experimental medicine. 2024;221(7). DOI: 10.1084/jem.20221122.

  • Guo H, Rogg M, Keller J, Scherzinger AK, Jäckel J, Meyer C, Sammarco A, Helmstädter M, Gorka O, Groß O, Schell C, Bechtel-Walz W. ADP-Ribosylation Factor-Interacting Protein 2 Acts as a Novel Regulator of Mitophagy and Autophagy in Podocytes in Diabetic Nephropathy. Antioxidants (Basel, Switzerland). 2024;13(1). DOI: 10.3390/antiox13010081.

  • Riedhammer KM, Nguyen TT, Koşukcu C, Calzada-Wack J, Li Y, Assia Batzir N, Saygılı S, Wimmers V, Kim GJ, Chrysanthou M, Bakey Z, Sofrin-Drucker E, Kraiger M, Sanz-Moreno A, Amarie OV, Rathkolb B, Klein-Rodewald T, Garrett L, Hölter SM, Seisenberger C, Haug S, Schlosser P, Marschall S, Wurst W, Fuchs H, Gailus-Durner V, Wuttke M, Hrabe de Angelis M, Ćomić J, Akgün Doğan Ö, Özlük Y, Taşdemir M, Ağbaş A, Canpolat N, Orenstein N, Çalışkan S, Weber RG, Bergmann C, Jeanpierre C, Saunier S, Lim TY, Hildebrandt F, Alhaddad B, Basel-Salmon L, Borovitz Y, Wu K, Antony D, Matschkal J, Schaaf CW, Renders L, Schmaderer C, Rogg M, Schell C, Meitinger T, Heemann U, Köttgen A, Arnold SJ, Ozaltin F, Schmidts M, Hoefele J. Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT). Kidney international. 2024;105(4):844-64. DOI: 10.1016/j.kint.2023.11.032.

  • Dettmer-Monaco V, Weißert K, Ammann S, Monaco G, Lei L, Gräßel L, Rhiel M, Rositzka J, Kaufmann MM, Geiger K, Andrieux G, Lao J, Thoulass G, Schell C, Boerries M, Illert AL, Cornu TI, Ehl S, Aichele P, Cathomen T. Gene editing of hematopoietic stem cells restores T-cell response in familial hemophagocytic lymphohistiocytosis. The Journal of allergy and clinical immunology. 2024;153(1):243-55.e14. DOI: 10.1016/j.jaci.2023.08.003.

 

2023

  • Rogg M, Maier JI, Helmstädter M, Sammarco A, Kliewe F, Kretz O, Weißer L, Van Wymersch C, Findeisen K, Koessinger AL, Tsoy O, Baumbach J, Grabbert M, Werner M, Huber TB, Endlich N, Schilling O, Schell C. A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions. Cells. 2023;12(13). DOI: 10.3390/cells12131795.

  • Vöing K, Michgehl U, Mertens ND, Picciotto C, Maywald ML, Goretzko J, Waimann S, Gilhaus K, Rogg M, Schell C, Klingauf J, Tsytsyura Y, Hansen U, van Marck V, Edinger AL, Vollenbröker B, Rescher U, Braun DA, George B, Weide T, Pavenstädt H. Disruption of the Rab7-Dependent Final Common Pathway of Endosomal and Autophagic Processing Results in a Severe Podocytopathy. Journal of the American Society of Nephrology : JASN. 2023;34(7):1191-206. DOI: 10.1681/asn.0000000000000126.

  • Braun F, Abed A, Sellung D, Rogg M, Woidy M, Eikrem O, Wanner N, Gambardella J, Laufer SD, Haas F, Wong MN, Dumoulin B, Rischke P, Mühlig A, Sachs W, von Cossel K, Schulz K, Muschol N, Gersting SW, Muntau AC, Kretz O, Hahn O, Rinschen MM, Mauer M, Bork T, Grahammer F, Liang W, Eierhoff T, Römer W, Hansen A, Meyer-Schwesinger C, Iaccarino G, Tøndel C, Marti HP, Najafian B, Puelles VG, Schell C, Huber TB. Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy. The Journal of clinical investigation. 2023;133(11). DOI: 10.1172/jci157782.

  • Hagmann H, Khayyat NH, Matin M, Oezel C, Chen H, Schauss A, Schell C, Benzing T, Dryer S, Brinkkoetter PT. Capsazepine (CPZ) Inhibits TRPC6 Conductance and Is Protective in Adriamycin-Induced Nephropathy and Diabetic Glomerulopathy. Cells. 2023;12(2). DOI: 10.3390/cells12020271.

  • Strohmeier V, Andrieux G, Unger S, Pascual-Reguant A, Klocperk A, Seidl M, Marques OC, Eckert M, Gräwe K, Shabani M, von Spee-Mayer C, Friedmann D, Harder I, Gutenberger S, Keller B, Proietti M, Bulashevska A, Grimbacher B, Provaznik J, Benes V, Goldacker S, Schell C, Hauser AE, Boerries M, Hasselblatt P, Warnatz K. Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency-Associated Villous Atrophy and Norovirus Infection. Journal of clinical immunology. 2023;43(2):371-90. DOI: 10.1007/s10875-022-01379-2.

2022

  • Rückert T, Andrieux G, Boerries M, Hanke-Müller K, Woessner NM, Doetsch S, Schell C, Aumann K, Kolter J, Schmitt-Graeff A, Schiff M, Braun LM, Haring E, Kissel S, Siranosian BA, Bhatt AS, Nordkild P, Wehkamp J, Jensen BAH, Minguet S, Duyster J, Zeiser R, Köhler N. Human β-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling. Science translational medicine. 2022;14(676):eabp9675. DOI: 10.1126/scitranslmed.abp9675.

  • Seidel P, Rubarth A, Zodel K, Peighambari A, Neumann F, Federkiel Y, Huang H, Hoefflin R, Adlesic M, Witt C, Hoffmann DJ, Metzger P, Lindemann RK, Zenke FT, Schell C, Boerries M, von Elverfeldt D, Reichardt W, Follo M, Albers J, Frew IJ. ATR represents a therapeutic vulnerability in clear cell renal cell carcinoma. JCI insight. 2022;7(24). DOI: 10.1172/jci.insight.156087.

  • Weißert K, Ammann S, Kögl T, Dettmer-Monaco V, Schell C, Cathomen T, Ehl S, Aichele P. Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH). EMBO molecular medicine. 2022;14(12):e16085. DOI: 10.15252/emmm.202216085.

  • Marinescu IM, Rogg M, Spohn S, von Büren M, Kamps M, Jilg CA, Fountzila E, Papadopoulou K, Ceci L, Bettermann A, Ruf J, Benndorf M, Adebahr S, Zips D, Grosu AL, Schell C, Zamboglou C. Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters. Radiation oncology (London, England). 2022;17(1):163. DOI: 10.1186/s13014-022-02131-1.

  • Jiao H, Wachsmuth L, Wolf S, Lohmann J, Nagata M, Kaya GG, Oikonomou N, Kondylis V, Rogg M, Diebold M, Tröder SE, Zevnik B, Prinz M, Schell C, Young GR, Kassiotis G, Pasparakis M. ADAR1 averts fatal type I interferon induction by ZBP1. Nature. 2022;607(7920):776-83. DOI: 10.1038/s41586-022-04878-9.

  • Globig AM, Mayer LS, Heeg M, Andrieux G, Ku M, Otto-Mora P, Hipp AV, Zoldan K, Pattekar A, Rana N, Schell C, Boerries M, Hofmann M, Neumann-Haefelin C, Kuellmer A, Schmidt A, Boettler T, Tomov V, Thimme R, Hasselblatt P, Bengsch B. Exhaustion of CD39-Expressing CD8(+) T Cells in Crohn's Disease Is Linked to Clinical Outcome. Gastroenterology. 2022;163(4):965-81.e31. DOI: 10.1053/j.gastro.2022.06.045.

  • Rogg M, Maier JI, Ehle M, Sammarco A, Schilling O, Werner M, Schell C. NUP133 Controls Nuclear Pore Assembly, Transcriptome Composition, and Cytoskeleton Regulation in Podocytes. Cells. 2022;11(8). DOI: 10.3390/cells11081259.

  • Bork T, Liang W, Kretz O, Lagies S, Yamahara K, Hernando-Erhard C, Helmstädter M, Schell C, Kammerer B, Huber TB. BECLIN1 Is Essential for Podocyte Secretory Pathways Mediating VEGF Secretion and Podocyte-Endothelial Crosstalk. International journal of molecular sciences. 2022;23(7). DOI: 10.3390/ijms23073825.

  • Devane J, Ott E, Olinger EG, Epting D, Decker E, Friedrich A, Bachmann N, Renschler G, Eisenberger T, Briem-Richter A, Grabhorn EF, Powell L, Wilson IJ, Rice SJ, Miles CG, Wood K, Trivedi P, Hirschfield G, Pietrobattista A, Wohler E, Mezina A, Sobreira N, Agolini E, Maggiore G, Dahmer-Heath M, Yilmaz A, Boerries M, Metzger P, Schell C, Grünewald I, Konrad M, König J, Schlevogt B, Sayer JA, Bergmann C. Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations. American journal of human genetics. 2022;109(5):928-43. DOI: 10.1016/j.ajhg.2022.03.015.

  • Rogg M, Maier JI, Van Wymersch C, Helmstädter M, Sammarco A, Lindenmeyer M, Zareba P, Montanez E, Walz G, Werner M, Endlich N, Benzing T, Huber TB, Schell C. α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier. Journal of the American Society of Nephrology : JASN. 2022;33(4):786-808. DOI: 10.1681/asn.2021101319.

2021

  • Maier JI, Rogg M, Helmstädter M, Sammarco A, Schilling O, Sabass B, Miner JH, Dengjel J, Walz G, Werner M, Huber TB, Schell C.
    EPB41L5 controls podocyte extracellular matrix assembly by adhesome-dependent force transmission.
    Cell Rep. 2021 Mar 23;34(12):108883.
    doi: 10.1016/j.celrep.2021.108883. PMID: 33761352.

  • Rogg M, Maier JI, Dotzauer R, Artelt N, Kretz O, Helmstädter M, Abed A, Sammarco A, Sigle A, Sellung D, Dinse P, Reiche K, Yasuda-Yamahara M, Biniossek ML, Walz G, Werner M, Endlich N, Schilling O, Huber TB, Schell C.
    SRGAP1 Controls Small Rho GTPases To Regulate Podocyte Foot Process Maintenance.
    J Am Soc Nephrol. 2021 Mar;32(3):563-579.
    doi: 10.1681/ASN.2020081126. Epub 2021 Jan 29. PMID: 33514561; PMCID: PMC7920176.
     
  • Maier JI, Rogg M, Helmstädter M, Sammarco A, Walz G, Werner M, Schell C. A.
    Novel Model for Nephrotic Syndrome Reveals Associated Dysbiosis of the Gut Microbiome and Extramedullary Hematopoiesis.
    Cells. 2021 Jun 15;10(6):1509.
    doi: 10.3390/cells10061509. PMID: 34203913; PMCID: PMC8232754.
     
  • Schlager D, Schulte A, Schütz J, Brandenburg A, Schell C, Lamrini S, Vogel M, Teichmann HO, Miernik A.
    Laser-guided real-time automatic target identification for endoscopic stone lithotripsy: a two-arm in vivo porcine comparison study.
    World J Urol. 2021 Jul; 39(7):2719-2726. doi: 10.1007/s00345-020-03452-0.
    Epub 2020 Sep 22. PMID: 32960325; PMCID: PMC8332575.
     

2020

  • Liang W, Yamahara K, Hernando-Erhard C, Lagies S, Wanner N, Liang H, Schell C, Kammerer B, Huber TB, Bork T.
    A reciprocal regulation of spermidine and autophagy in podocytes maintains the filtration barrier.
    Kidney Int. 2020 Dec; 98(6):1434-1448.
    doi: 10.1016/j.kint.2020.06.016. Epub 2020 Jun 27. PMID: 32603735.

  • Hoefflin R, Harlander S, Schäfer S, Metzger P, Kuo F, Schönenberger D, Adlesic M, Peighambari A, Seidel P, Chen CY, Consenza-Contreras M, Jud A, Lahrmann B, Grabe N, Heide D, Uhl FM, Chan TA, Duyster J, Zeiser R, Schell C, Heikenwalder M, Schilling O, Hakimi AA, Boerries M, Frew IJ.
    HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice.
    Nat Commun. 2020 Aug 17;11(1):4111.
    doi: 10.1038/s41467-020-17873-3. PMID: 32807776; PMCID: PMC7431415.

2019

  • Bork T, Liang W, Yamahara K, Lee P, Tian Z, Liu S, Schell C, Thedieck K, Hartleben B, Patel K, Tharaux PL, Lenoir O, Huber TB.
    Podocytes maintain high basal levels of autophagy independent of mtor signaling.
    Autophagy. 2019 Dec 23:1-17.
    doi: 10.1080/15548627.2019.1705007. [Epub ahead of print] PubMed PMID: 31865844

  • Brinkkoetter PT, Bork T, Salou S, Liang W, Mizi A, Özel C, Koehler S, Hagmann HH, Ising C, Kuczkowski A, Schnyder S, Abed A, Schermer B, Benzing T, Kretz O, Puelles VG, Lagies S, Schlimpert M, Kammerer B, Handschin C, Schell C, Huber TB.
    Anaerobic Glycolysis Maintains the Glomerular Filtration Barrier Independent of Mitochondrial Metabolism and Dynamics.
    Cell Rep. 2019 Apr 30;27(5):1551-1566.e5.
    doi: 10.1016/j.celrep.2019.04.012. PubMed PMID: 31042480; PubMed Central PMCID: PMC6506687.

  • Huang Y, Schell C, Huber TB, Şimşek AN, Hersch N, Merkel R, Gompper G, Sabass B.
    Traction force microscopy with optimized regularization and automated Bayesian parameter selection for comparing cells.
    Sci Rep. 2019 Jan 24;9(1):539.
    doi: 10.1038/s41598-018-36896-x. PubMed PMID: 30679578; PubMed Central PMCID: PMC6345967.

2018

  • Schell C, Sabass B, Helmstaedter M, Geist F, Abed A, Yasuda-Yamahara M, Sigle A, Maier JI, Grahammer F, Siegerist F, Artelt N, Endlich N, Kerjaschki D, Arnold HH, Dengjel J, Rogg M, Huber TB.
    ARP3 Controls the Podocyte Architecture at the Kidney Filtration Barrier.
    Dev Cell. 2018 Dec 17;47(6):741-757.e8.
    doi: 10.1016/j.devcel.2018.11.011. Epub 2018 Nov 29. PubMed PMID: 30503751; PubMed Central PMCID: PMC6302147.

  • Drendel V, Heckelmann B, Schell C, Kook L, Biniossek ML, Werner M, Jilg CA, Schilling O.
    Proteomic distinction of renal oncocytomas and chromophobe renal cell carcinomas.
    Clin Proteomics. 2018 Aug 3;15:25.
    doi: 10.1186/s12014-018-9200-6. eCollection 2018. PubMed PMID: 30087584; PubMed Central PMCID: PMC6074034.

  • Yasuda-Yamahara M, Rogg M, Yamahara K, Maier JI, Huber TB, Schell C.
    AIF1L regulates actomyosin contractility and filopodial extensions in human podocytes.
    PLoS One. 2018 Jul 12;13(7):e0200487.
    doi: 10.1371/journal.pone.0200487. eCollection 2018. PubMed PMID: 30001384; PubMed Central PMCID: PMC6042786.

  • Yasuda-Yamahara M, Rogg M, Frimmel J, Trachte P, Helmstaedter M, Schroder P, Schiffer M, Schell C, Huber TB.
    FERMT2 links cortical actin structures, plasma membrane tension and focal adhesion function to stabilize podocyte morphology.
    Matrix Biol. 2018 Aug;68-69:263-279.
    doi: 10.1016/j.matbio.2018.01.003. Epub 2018 Jan 11. PubMed PMID: 29337051.

2017

  • 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 anti-proliferative and anti-migratory exoprotease.
    Oncotarget. 2017 Oct 19;8(59):100066-100078.
    doi: 10.18632/oncotarget.21929. eCollection 2017 Nov 21. PubMed PMID: 29245961; PubMed Central PMCID: PMC5725003.

  • Rogg M, Yasuda-Yamahara M, Abed A, Dinse P, Helmstädter 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. 2017 Nov 21;7(1):15910.
    doi: 10.1038/s41598-017-15844-1. PubMed PMID: 29162887; PubMed Central PMCID: PMC5698439.

  • Schell C, Rogg M, Suhm M, Helmstädter M, Sellung D, Yasuda-Yamahara M, Kretz O, Küttner V, Suleiman H, Kollipara L, Zahedi RP, Sickmann A, Eimer S, Shaw AS, Kramer-Zucker A, Hirano-Kobayashi M, Abe T, Aizawa S, Grahammer F, Hartleben B, Dengjel J, Huber TB.
    The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier.
    Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):E4621-E4630.
    doi: 10.1073/pnas.1617004114. Epub 2017 May 23. PubMed PMID: 28536193; PubMed Central PMCID: PMC5468651.

Join our Team

We are continously looking for talented postdocs and PhD/Medical students. If you are interested please send your CV and a letter of intent to christoph.schell@uniklinik-freiburg.de

Kontakt Forschung

Generelle Anfragen zur Forschung am Institut
pathologie.projektkoord@uniklinik-freiburg.de

Forschungsverbünde:

Institut für Klinische Pathologie
Universitätsklinikum Freiburg
Breisacher Str. 115a
79106 Freiburg
Tel.: +49 761 270 80060 (Sekretariat)
Fax: +49 761 270-80040
pathologie.direktion@uniklinik-freiburg.de

Postanschrift:
Postfach 214
79002 Freiburg