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 Forschungsbericht für das Jahr 2007

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
  • Prof. Dr. Andreas Hecht, Gruppenleiter
  • PD Dr. Ulrich Maurer, Gruppenleiter
  • Prof. Dr. Friedrich Siebert, Gruppenleiter
  • PD Dr. med. Oliver Opitz, Gruppenleiter
  • Dr. Felix Beuschlein, Gruppenleiter
  • Dr. Céline Charvet
  • Dr. Thomas Reinheckel, Gruppenleiter
  • Dr. Marlene Tacke (geb. Fischer)
  • PD Dr. Martin Trepel, Gruppenleiter
  • PD Dr. Reiner Vogel, Gruppenleiter
  • Dr. Robert Zeiser, Gruppenleiter
  • Dr. Ulrich vor dem Esche, AG Bessler
  • Dr. Jan Harder
  • Dr. Sarah Kaufmann
  • Dr. Urs Lichtenauer
  • Dr. Klaus Mittenbühler, AG Bessler
  • Dr. Carolin Oberle
  • Dr. Robert Pick
  • Dr. Uta Schurigt
  • Dr. Andreas Weise
  • Dr. Ekaterina Zaitseva
  • Prof. Dr. em. Wolfgang Bessler, Emeritus
Einträge in der Rubrik "Who is Who"

Finanzierung

  • Deutsche Krebshilfe, 10-6977 Re. "Die Bedeutung lysosomaler Cysteinproteasen für die Progression muriner und humaner epidermaler Karzinome". (Reinheckel)
  • DFG, He 2004/6-1, He 2004/6-2. "Funktionelle Diversifizierung von Signaltransduktionsmechanismen: Ausmaß und molekulare Grundlagen des genspezifischen regulatorischen Potentials von 'T-Cell Factor' DNA-Bindungsproteinen". (Hecht)
  • DFG. Re 1584/3-1 "Untersuchungen zu Funktionen der lysosomalen Proteasen Cathepsin H, Cathepsin E und Napsin in Lunge und Immunsystem". (Reinheckel)
  • EU, Framework 6, "Creation and biological analysis of tumors in novel protease gene knockout models." (Workpackage 2.1) "Detailed spatio-temporal examination of specific proteases and inhibitors in spontaneous mouse cancer models." (Workpackage 2.2)(Peters, Reinheckel)
  • EU. "Concerted Safety and Efficiency Evaluation of Retroviral Transgenesis for Gene Therapy of Inherited Diseases (Consert)". (von Kalle)
  • MWK, "Protease-selektive Inhibitor-basierte NMR-Marker". (Reinheckel, Peters)

Wissenschaftliche Projekte und Forschungsvorhaben


  • "Concerted Safety and Efficiency Evaluation of Retroviral Transgenesis for Gene Therapy of Inherited Diseases (Consert)"
    • Projektleitung: Prof. Dr. Christof von Kalle
    • Laufzeit: 01.11.2004 bis 31.10.2008
    • Details zum Projekt
  • "Creation and biological analysis of tumors in novel protease gene knockout models." (Workpackage 2.1) "Detailed spatio-temporal examination of specific proteases and inhibitors in spontaneous mouse cancer models." (Workpackage 2.2) Project full title: "Extracellular Proteases and the Caner Degradome: Innovative Diagnostic Markers, Therapeutic Targets and Tumour Imaging Agents."
  • "Die Bedeutung lysosomaler Cysteinproteasen für die Progression muriner und humaner epidermaler Karzinome"
    • Projektleitung: Dr. Thomas Reinheckel
    • Laufzeit: 01.04.2006 bis 31.03.2009
    • Details zum Projekt
  • "Funktionelle Diversifizierung von Signaltransduktionsmechanismen: Ausmaß und molekulare Grundlagen des genspezifischen regulatorischen Potentials von 'T-Cell Factor' DNA-Bindungsproteinen"
  • "Mouse organogenesis regulated by apoptosis: the role of serine proteases"
    • Projektleitung: Prof. Dr. Christoph Borner
    • Laufzeit: 01.05.2005 bis 31.12.2009
    • Details zum Projekt
  • "Protease-selektive Inhibitor-basierte NMR-Marker"
    • Projektleitung: Dr. Thomas Reinheckel, Prof. Dr. Christoph Peters
    • Laufzeit: 01.05.2006 bis 30.04.2008
    • Details zum Projekt
  • "Untersuchungen zu Funktionen der lysosomalen Proteasen Cathepsin H, Cathepsin E und Napsin in Lunge und Immunsystem"
    • Projektleitung: Dr. Thomas Reinheckel
    • Laufzeit: 01.05.2004 bis 31.12.2007
    • Details zum Projekt

Wissenschaftliche Publikationen

Originalarbeiten in wissenschaftlichen Fachzeitschriften:
  • Ball CR, Pilz IH, Schmidt M, Fessler S, Williams DA, von Kalle C, Glimm H: Stable differentiation and clonality of murine long-term hematopoiesis after extended reduced-intensity selection for MGMT P140K transgene expression. Blood, 2007; 110 (6): 1779-1787.
  • Bartl FJ, Vogel R: Structural and functional properties of metarhodopsin III: recent spectroscopic studies on deactivation pathways of rhodopsin. Phys Chem Chem Phys, 2007; 9 (14): 1648-1658.
  • Becart S, Charvet C, Canonigo Balancio AJ, De Trez C, Tanaka Y, Duan W, Ware C, Croft M, Altman A: SLAT regulates Th1 and Th2 inflammatory responses by controlling Ca2+/NFAT signaling. J Clin Invest, 2007; 117 (8): 2164-2175.
  • Beuschlein F, Reincke M: [Therapy-resistant hypertension-the endocrinological view] MMW Fortschr Med, 2007; 149 (9): 29-32.
  • Bielohuby M, Herbach N, Wanke R, Maser-Gluth C, Beuschlein F, Wolf E, Hoeflich A: Growth analysis of the mouse adrenal gland from weaning to adulthood: time- and gender-dependent alterations of cell size and number in the cortical compartment. Am J Physiol-endoc M, 2007; 293 (1): E139-E146.
  • Binder M, Vogtle FN, Michelfelder S, Muller F, Illerhaus G, Sundararajan S, Mertelsmann R, Trepel M: Identification of their epitope reveals the structural basis for the mechanism of action of the immunosuppressive antibodies basiliximab and daclizumab. Cancer Res, 2007; 67 (8): 3518-3523.
  • Bojic L, Petelin A, Stoka V, Reinheckel T, Peters C, Turk V, Turk B: Cysteine cathepsins are not involved in Fas/CD95 signalling in primary skin fibroblasts. FEBS Lett, 2007; 581 (27): 5185-5190.
  • Borner C, Hollt V, Kraus J: Activation of human T cells induces upregulation of cannabinoid receptor type 1 transcription. Neuroimmunomodulat, 2007; 14 (6): 281-286. : http://dx.doi.org/10.1159/000117809
  • Borner C, Hollt V, Sebald W, Kraus J: Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids. J Leukocyte Biol, 2007; 81 (1): 336-343. : http://dx.doi.org/10.1189/jlb.0306224
  • Borner C, Stumm R, Hollt V, Kraus J: Comparative analysis of mu-opioid receptor expression in immune and neuronal cells. J Neuroimmunol, 2007; 188 (1-2): 56-63. : http://dx.doi.org/10.1016/j.jneuroim.2007.05.007
  • Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, Fitzgerald P, Guio-Carrion A, Waterhouse NJ, Li CW, Mari B, Barbry P, Newmeyer DD, Beere HM, Green DR: GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell, 2007; 129 (5): 983-997.
  • Engelhardt M, Zeiser R, Ihorst G, Finke J, Muller CI: High-dose chemotherapy and autologous peripheral blood stem cell transplantation in adult patients with high-risk or advanced Ewing and soft tissue sarcoma. J Cancer Res Clin, 2007; 133 (1): 1-11.
  • Fehrenbach K, Port F, Grochowy G, Kalis C, Bessler W, Galanos C, Krystal G, Freudenberg M, Huber M: Stimulation of mast cells via FcvarepsilonR1 and TLR2: The type of ligand determines the outcome. Mol Immunol, 2007; 44 (8): 2097-2104.
  • Fernandez I, Zeiser R, Karsunky H, Kambham N, Beilhack A, Soderstrom K, Negrin RS, Engleman E: CD101 surface expression discriminates potency among murine FoxP3+ regulatory T cells. J Immunol, 2007; 179 (5): 2808-2814.
  • Geissler E, Hecht AM, Horkay F: Scaling equations for a biopolymer in salt solution. Phys Rev Lett, 2007; 99 (26): 267801-267801.
  • Gorczynski RM, Alexander C, Bessler W, Brandenburg K, Fournier K, Mach JP, Mueller S, Rietschel ET, Ulmer AJ, Waelli T, Zahringer U, Khatri I: An alteration in the levels of populations of CD4+ Treg is in part responsible for altered cytokine production by cells of aged mice which follows injection with a fetal liver extract. Immunol Lett, 2007; 109 (2): 101-112.
  • Grunow R, Porsch-Ozcurumez M, Splettstoesser W, Buckendahl A, Hahn U, Beyer W, Bohm R, Huber M, vd Esche U, Bessler W, Frangoulidis D, Finke EJ: Monitoring of ELISA-reactive antibodies against anthrax protective antigen (PA), lethal factor (LF), and toxin-neutralising antibodies in serum of individuals vaccinated against anthrax with the PA-based UK anthrax vaccine. Vaccine, 2007; 25 (18): 3679-3683.
  • Hajitou A, Rangel R, Trepel M, Soghomonyan S, Gelovani JG, Alauddin MM, Pasqualini R, Arap W: Design and construction of targeted AAVP vectors for mammalian cell transduction. Nat Protoc, 2007; 2 (3): 523-531.
  • Harder J, Kummer O, Olschewski M, Otto F, Blum HE, Opitz O: Prognostic relevance of carbohydrate antigen 19-9 levels in patients with advanced biliary tract cancer. Cancer Epidem Biomar, 2007; 16 (10): 2097-2100.
  • Hershkovitz L, Beuschlein F, Klammer S, Krup M, Weinstein Y: Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone. Endocrinology, 2007; 148 (3): 976-988.
  • Hirsch C, Campano LM, Wohrle S, Hecht A: Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures. Exp Cell Res, 2007; 313 (3): 572-587. : http://dx.doi.org/10.1016/j.yexcr.2006.11.002
  • Hirsch C, Campano LM, Wöhrle S, Hecht A: Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures. Exp Cell Res, 2007; 313: 572-587.
  • Jager S, Jahnke A, Wilmes T, Adebahr S, Vogtle FN, Delima-Hahn E, Pfeifer D, Berg T, Lubbert M, Trepel M: Leukemia-targeting ligands isolated from phage-display peptide libraries. Leukemia, 2007; 21 (3): 411-420.
  • Kitamoto S, Sukhova GK, Sun J, Yang M, Libby P, Love V, Duramad P, Sun C, Zhang Y, Yang X, Peters C, Shi GP: Cathepsin L deficiency reduces diet-induced atherosclerosis in low-density lipoprotein receptor-knockout mice. Circulation, 2007; 115 (15): 2065-2075.
  • Lichtenauer UD, Duchniewicz M, Kolanczyk M, Hoeflich A, Hahner S, Else T, Bicknell AB, Zemojtel T, Stallings NR, Schulte DM, Kamps MP, Hammer GD, Scheele JS, Beuschlein F: Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis. Endocrinology, 2007; 148 (2): 693-704.
  • Michelfelder S, Lee MK, deLima-Hahn E, Wilmes T, Kaul F, Muller O, Kleinschmidt JA, Trepel M: Vectors selected from adeno-associated viral display peptide libraries for leukemia cell-targeted cytotoxic gene therapy. Exp Hematol, 2007; 35 (12): 1766-1776.
  • Mukhopadhyay S, Almehed D, Garg U, Frauendorf S, Li T, Rao PV, Wang X, Ghugre SS, Carpenter MP, Gros S, Hecht A, Janssens RV, Kondev FG, Lauritsen T, Seweryniak D, Zhu S: From chiral vibration to static chirality in (135)Nd. Phys Rev Lett, 2007; 99 (17): 172501-172501.
  • Murgida DH, von Stetten D, Hildebrandt P, Schwinte P, Siebert F, Sharda S, Gartner W, Mroginski MA: The chromophore structures of the Pr States in plant and bacterial phytochromes. Biophys J, 2007; 93 (7): 2410-2417.
  • Nguyen VH, Zeiser R, Dasilva DL, Chang DS, Beilhack A, Contag CH, Negrin RS: In vivo dynamics of regulatory T-cell trafficking and survival predict effective strategies to control graft-versus-host disease following allogeneic transplantation. Blood, 2007; 109 (6): 2649-2656.
  • Sanjuan Szklarz LK, Kozjak-Pavlovic V, Vogtle FN, Chacinska A, Milenkovic D, Vogel S, Durr M, Westermann B, Guiard B, Martinou JC, Borner C, Pfanner N, Meisinger C: Preprotein transport machineries of yeast mitochondrial outer membrane are not required for Bax-induced release of intermembrane space proteins. J Mol Biol, 2007; 368 (1): 44-54.
  • Schmidt M, Schwarzwaelder K, Bartholomae C, Zaoui K, Ball C, Pilz I, Braun S, Glimm H, von Kalle C: High-resolution insertion-site analysis by linear amplification-mediated PCR. Nat Methods, 2007; 4 (12): 1051-1057.
  • Schwarzwaelder K, Howe SJ, Schmidt M, Brugman MH, Deichmann A, Glimm H, Schmidt S, Prinz C, Wissler M, King DJ, Zhang F, Parsley KL, Gilmour KC, Sinclair J, Bayford J, Peraj R, Pike-Overzet K, Staal FJ, de Ridder D, Kinnon C, Abel U, Wagemaker G, Gaspar HB, Thrasher AJ, von Kalle C: Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo. J Clin Invest, 2007; 117 (8): 2241-2249.
  • Seweryniak D, Carpenter MP, Gros S, Hecht AA, Hoteling N, Janssens RV, Khoo TL, Lauritsen T, Lister CJ, Lotay G, Peterson D, Robinson AP, Walters WB, Wang X, Woods PJ, Zhu S: Single-neutron states in (101)Sn. Phys Rev Lett, 2007; 99 (2): 022504-022504.
  • Slawik M, Klawitter B, Meiser E, Schories M, Zwermann O, Borm K, Peper M, Lubrich B, Hug MJ, Nauck M, Olschewski M, Beuschlein F, Reincke M: Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine. J Clin Endocr Metab, 2007; 92 (11): 4115-4122.
  • Soghomonyan S, Hajitou A, Rangel R, Trepel M, Pasqualini R, Arap W, Gelovani JG, Alauddin MM: Molecular PET imaging of HSV1-tk reporter gene expression using [18F]FEAU. Nat Protoc, 2007; 2 (2): 416-423.
  • Spiller S, Dreher S, Meng G, Grabiec A, Thomas W, Hartung T, Pfeffer K, Hochrein H, Brade H, Bessler W, Wagner H, Kirschning CJ: Cellular recognition of trimyristoylated peptide or enterobacterial lipopolysaccharide via both TLR2 and TLR4. J Biol Chem, 2007; 282 (18): 13190-13198.
  • Spira D, Stypmann J, Tobin DJ, Petermann I, Mayer C, Hagemann S, Vasiljeva O, Gunther T, Schule R, Peters C, Reinheckel T: Cell Type-specific Functions of the Lysosomal Protease Cathepsin L in the Heart. J Biol Chem, 2007; 282 (51): 37045-37052.
  • Tang XD, Rehm KE, Ahmad I, Brune CR, Champagne A, Greene JP, Hecht AA, Henderson D, Janssens RV, Jiang CL, Jisonna L, Kahl D, Moore EF, Notani M, Pardo RC, Patel N, Paul M, Savard G, Schiffer JP, Segel RE, Sinha S, Shumard B, Wuosmaa AH: New determination of the astrophysical S factor SE1 of the 12C(alpha,gamma)16O reaction. Phys Rev Lett, 2007; 99 (5): 052502-052502.
  • Tiwari N, Garbi N, Reinheckel T, Moldenhauer G, Hammerling GJ, Momburg F: A transporter associated with antigen-processing independent vacuolar pathway for the MHC class I-mediated presentation of endogenous transmembrane proteins. J Immunol, 2007; 178 (12): 7932-7942.
  • Vasiljeva O, Reinheckel T, Peters C, Turk D, Turk V, Turk B: Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Design, 2007; 13 (4): 387-403.
  • Vogel R, Martell S, Mahalingam M, Engelhard M, Siebert F: Interaction of a G protein-coupled receptor with a G protein-derived peptide induces structural changes in both peptide and receptor: a Fourier-transform infrared study using isotopically labeled peptides. J Mol Biol, 2007; 366 (5): 1580-1588.
  • Vogel R, Sakmar TP, Sheves M, Siebert F: Coupling of protonation switches during rhodopsin activation. Photochem Photobiol, 2007; 83 (2): 286-292.
  • Wohrle S, Wallmen B, Hecht A: Differential control of Wnt target genes involves epigenetic mechanisms and selective promoter occupancy by T-cell factors. Mol Cell Biol, 2007; 27 (23): 8164-8177.
  • Wohrle S, Wallmen B, Hecht A: Differential control of Wnt target genes involves epigenetic mechanisms and selective promoter occupancy by T-cell factors. Mol Cell Biol, 2007; 27 (23): 8164-8177. : http://dx.doi.org/10.1128/MCB.00555-07
  • Yamasaki R, Zhang J, Koshiishi I, Sastradipura Suniarti DF, Wu Z, Peters C, Schwake M, Uchiyama Y, Kira J, Saftig P, Utsumi H, Nakanishi H: Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice. Mol Cell Neurosci, 2007; 35 (4): 573-584.
  • Yoder NC, Kalsani V, Schuy S, Vogel R, Janshoff A, Kumar K: Nanoscale patterning in mixed fluorocarbon-hydrocarbon phospholipid bilayers. J Am Chem Soc, 2007; 129 (29): 9037-9043.
  • Zeiser R, Nguyen VH, Hou JZ, Beilhack A, Zambricki E, Buess M, Contag CH, Negrin RS: Early CD30 signaling is critical for adoptively transferred CD4+CD25+ regulatory T cells in prevention of acute graft-versus-host disease. Blood, 2007; 109 (5): 2225-2233.
  • Zeiser R, Youssef S, Baker J, Kambham N, Steinman L, Negrin RS: Preemptive HMG-CoA reductase inhibition provides graft-versus-host disease protection by Th-2 polarization while sparing graft-versus-leukemia activity. Blood, 2007; 110 (13): 4588-4598.
  • Zeiser R, Zambricki EA, Leveson-Gower D, Kambham N, Beilhack A, Negrin RS: Host-derived interleukin-18 differentially impacts regulatory and conventional T cell expansion during acute graft-versus-host disease. Biol Blood Marrow Tr, 2007; 13 (12): 1427-1438.
  • Zwermann O, Braun AC, Lalli E, Sassone-Corsi P, Beuschlein F, Reincke M: Regulation of human MC2-R gene expression by CREB, CREM, and ICER in the adrenocortical cell line Y1. Horm Metab Res, 2007; 39 (8): 560-566.

Besondere wissenschaftliche Aktivitäten

Abschlussarbeiten

Promotionen
  • Hirsch, Cordula: Untersuchung zum Einfluss des kanonischen Wnt-Signalwegs auf Proliferation und Differenzierung neuraler Vorläuferzellen aus dem Vorderhirn der Maus (Erstgutachter/in Prof. Dr. Andreas Hecht), 2007.
  • Winter, Daniel: A setup for time-resolved step-scan spectroscopy of samples with irreversible photoreaction : first results for the membrane protein rhodopsin (Erstgutachter/in Prof. Dr. Friedrich Siebert), 2007.