Institut für Molekulare Medizin und Zellforschung (IMMZ)

Zentrum für Biochemie und Molekulare Zellforschung (ZBMZ)

Wissenschaftliche Mitarbeiterinnen und Mitarbeiter

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 und Systemmedizin
• Tumorinvasion und Metastasierung

Finanzierung

• siehe: www.mol-med.uni-freiburg.de

Wissenschaftliche Publikationen

• Bildl W *, Haupt A *, Muller CS *, Biniossek ML, Thumfart JO, Huber B, Fakler B, Schulte U: Extending the Dynamic Range of Label-free Mass Spectrometric Quantification of Affinity Purifications. Mol Cell Proteomics, 2012; 11 (2): 007955-1-007955-12. : http://dx.doi.org/10.1074/mcp.M111.007955
• Biniossek ML, Schilling O: Enhanced identification of peptides lacking basic residues by LC-ESI-MS/MS analysis of singly charged peptides. Proteomics, 2012; 12 (9): 1303-1309. : http://dx.doi.org/10.1002/pmic.201100569
• Borner C, Hollt V, Kraus J: Mechanisms of the inhibition of nuclear factor-kappaB by morphine in neuronal cells. Mol Pharmacol, 2012; 81 (4): 587-597. : http://dx.doi.org/10.1124/mol.111.076620
• Borner C, Martella E, Hollt V, Kraus J: Regulation of opioid and cannabinoid receptor genes in human neuroblastoma and T cells by the epigenetic modifiers trichostatin A and 5-aza-2'-deoxycytidine. Neuroimmunomodulat, 2012; 19 (3): 180-186. : http://dx.doi.org/10.1159/000331474
• Bronson WH, Forsh D, Qureshi SA, Deiner SG, Weisz DJ, Hecht AC: Evolving compartment syndrome detected by loss of somatosensory- and motor-evoked potential signals during cervical spine surgery. Orthopedics, 2012; 35 (9): e1453-e1456. : http://dx.doi.org/10.3928/01477447-20120822-40
• Brummer TH, Heikkinen A, Jalkanen J, Fraser J, Makinen J, Tomas E, Seppala T, Sjoberg J, Harkki P: Pharmaceutical thrombosis prophylaxis, bleeding complications and thromboembolism in a national cohort of hysterectomy for benign disease. Hum Reprod, 2012; 27 (6): 1628-1636. : http://dx.doi.org/10.1093/humrep/des103
• Casaburi R, Porszasz J, Hecht A, Tiep B, Albert RK, Anthonisen NR, Bailey WC, Connett JE, Cooper JA Jr, Criner GJ, Curtis J, Dransfield M, Lazarus SC, Make B, Martinez FJ, McEvoy C, Niewoehner DE, Reilly JJ, Scanlon P, Scharf SM, Sciurba FC, Woodruff P: Influence of lightweight ambulatory oxygen on oxygen use and activity patterns of COPD patients receiving long-term oxygen therapy. COPD, 2012; 9 (1): 3-11. : http://dx.doi.org/10.3109/15412555.2011.630048
• Diederich S, Sauerhering L, Weis M, Altmeppen H, Schaschke N, Reinheckel T, Erbar S, Maisner A: Activation of the Nipah Virus Fusion Protein in MDCK Cells Is Mediated by Cathepsin B within the Endosome-Recycling Compartment. J Virol, 2012; 86 (7): 3736-3745. : http://dx.doi.org/10.1128/JVI.06628-11
• Douglas Lu W, Funkelstein L, Toneff T, Reinheckel T, Peters C, Hook V: Cathepsin H functions as an aminopeptidase in secretory vesicles for production of enkephalin and galanin peptide neurotransmitters. J Neurochem, 2012; 122 (3): 512-522. : http://dx.doi.org/10.1111/j.1471-4159.2012.07788.x
• Ferreira KS, Kreutz C, Macnelly S, Neubert K, Haber A, Bogyo M, Timmer J, Borner C: Caspase-3 feeds back on caspase-8, Bid and XIAP in type I Fas signaling in primary mouse hepatocytes. Apoptosis, 2012; 17 (5): 503-515. : http://dx.doi.org/10.1007/s10495-011-0691-0
• Ferreira KS, Kreutz C, Macnelly S, Neubert K, Haber A, Bogyo M, Timmer J, Borner C: Caspase-3 feeds back on caspase-8, Bid and XIAP in type I Fas signaling in primary mouse hepatocytes. Apoptosis, 2012; 17 (5): 503-515. : http://dx.doi.org/10.1007/s10495-011-0691-0
• Goerke M, Eklund M, Sauer N, Rademacher M, Piepho HP, Borner C, Mosenthin R: Effect of feed intake level on ileal digestibilities of crude protein and amino acids in diets for piglets. J Sci Food Agr, 2012; 92 (6): 1261-1266. : http://dx.doi.org/10.1002/jsfa.4692
• Gopinathan A, Denicola GM, Frese KK, Cook N, Karreth FA, Mayerle J, Lerch MM, Reinheckel T, Tuveson DA: Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice. Gut, 2012; 61 (6): 877-884. : http://dx.doi.org/10.1136/gutjnl-2011-300850
• Grimm S, Horlacher M, Catalgol B, Hoehn A, Reinheckel T, Grune T: Cathepsins D and L reduce the toxicity of advanced glycation end products. Free Radical Bio Med, 2012; 52 (6): 1011-1023. : http://dx.doi.org/10.1016/j.freeradbiomed.2011.12.021
• Hertzen E, Johansson L, Kansal R, Hecht A, Dahesh S, Janos M, Nizet V, Kotb M, Norrby-Teglund A: Intracellular Streptococcus pyogenes in human macrophages display an altered gene expression profile. Plos One, 2012; 7 (4): e35218-e35218. : http://dx.doi.org/10.1371/journal.pone.0035218
• Holeiter G, Bischoff A, Braun AC, Huck B, Erlmann P, Schmid S, Herr R, Brummer T, Olayioye MA: The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens junctions integrity. Oncogenesis, 2012; 1: e13-e13. : http://dx.doi.org/10.1038/oncsis.2012.13
• Horkay F, Basser PJ, Hecht AM, Geissler E: Chondroitin Sulfate in Solution: Effects of Mono- and Divalent Salts. Macromolecules, 2012; 45 (6): 2882-2890. : http://dx.doi.org/10.1021/ma202693s
• Iatridis JC, Hecht AC: Commentary: Does needle injection cause disc degeneration? News in the continuing debate regarding pathophysiology associated with intradiscal injections. Spine J, 2012; 12 (4): 336-338. : http://dx.doi.org/10.1016/j.spinee.2012.03.006
• Joeckel LT, Wallich R, Metkar SS, Froelich CJ, Simon MM, Borner C: Interleukin-1R signaling is essential for induction of proapoptotic CD8 T cells, viral clearance, and pathology during lymphocytic choriomeningitis virus infection in mice. J Virol, 2012; 86 (16): 8713-8719. : http://dx.doi.org/10.1128/JVI.00682-12
• Joeckel LT, Wallich R, Metkar SS, Froelich CJ, Simon MM, Borner C: Interleukin-1R signaling is essential for induction of proapoptotic CD8 T cells, viral clearance, and pathology during lymphocytic choriomeningitis virus infection in mice. J Virol, 2012; 86 (16): 8713-8719. : http://dx.doi.org/10.1128/JVI.00682-12
• Jo J, Bengsch B, Seigel B, Rau SJ, Schmidt J, Bisse E, Aichele P, Aichele U, Joeckel L, Royer C, Sa Ferreira K, Borner C, Baumert TF, Blum HE, Lohmann V, Fischer R, Thimme R: Low perforin expression of early differentiated HCV-specific CD8+ T cells limits their hepatotoxic potential. J Hepatol, 2012; 57 (1): 9-16. : http://dx.doi.org/10.1016/j.jhep.2012.02.030
• Jo J, Bengsch B, Seigel B, Rau SJ, Schmidt J, Bisse E, Aichele P, Aichele U, Joeckel L, Royer C, Sa Ferreira K, Borner C, Baumert TF, Blum HE, Lohmann V, Fischer R, Thimme R: Low perforin expression of early differentiated HCV-specific CD8+ T cells limits their hepatotoxic potential. J Hepatol, 2012; 57 (1): 9-16. : http://dx.doi.org/10.1016/j.jhep.2012.02.030
• Kalyuga M, Gallego-Ortega D, Lee HJ, Roden DL, Cowley MJ, Caldon CE, Stone A, Allerdice SL, Valdes-Mora F, Launchbury R, Statham AL, Armstrong N, Alles MC, Young A, Egger A, Au W, Piggin CL, Evans CJ, Ledger A, Brummer T, Oakes SR, Kaplan W, Gee JM, Nicholson RI, Sutherland RL, Swarbrick A, Naylor MJ, Clark SJ, Carroll JS, Ormandy CJ: ELF5 Suppresses Estrogen Sensitivity and Underpins the Acquisition of Antiestrogen Resistance in Luminal Breast Cancer. Plos Biol, 2012; 10 (12) (online): e1001461-e1001461. : http://dx.doi.org/10.1371/journal.pbio.1001461
• Kalyuga M, Gallego-Ortega D, Lee HJ, Roden DL, Cowley MJ, Caldon CE, Stone A, Allerdice SL, Valdes-Mora F, Launchbury R, Statham AL, Armstrong N, Alles MC, Young A, Egger A, Au W, Piggin CL, Evans CJ, Ledger A, Brummer T, Oakes SR, Kaplan W, Gee JM, Nicholson RI, Sutherland RL, Swarbrick A, Naylor MJ, Clark SJ, Carroll JS, Ormandy CJ: ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer. Plos Biol, 2012; 10 (12): e1001461-e1001461. : http://dx.doi.org/10.1371/journal.pbio.1001461
• Kienzle C, Eisler SA, Villeneuve J, Brummer T, Olayioye MA, Hausser A: PKD controls mitotic Golgi complex fragmentation through a Raf-MEK1 pathway. Mol Biol Cell, 2012. : http://dx.doi.org/10.1091/mbc.E12-03-0198 (in Druck)
• Koike M, Shibata M, Ezaki J, Peters C, Saftig P, Kominami E, Uchiyama Y: Differences in expression patterns of cathepsin C/dipeptidyl peptidase I in normal, pathological and aged mouse central nervous system. Eur J Neurosci, 2012. : http://dx.doi.org/10.1111/ejn.12096 (in Druck)
• Leprivier G, Rufini A, Garcia-Saez AJ, Borner C, Rotblat B: 7th Tuscany Retreat on Cancer Research: genetic profiling, resistance mechanism and novel treatment concepts in cancer. Cell Death Differ, 2012; 19 (3): 546-548. : http://dx.doi.org/10.1038/cdd.2011.186
• Lin JD, Koehler SM, Garcia RA, Qureshi SA, Hecht AC: Intraosseous ganglion cyst within the L4 lamina causing spinal stenosis. Spine J, 2012; 12 (11): e9-12. : http://dx.doi.org/10.1016/j.spinee.2012.10.018
• Marzi A, Reinheckel T, Feldmann H: Cathepsin B & L are not required for ebola virus replication. Plos Neglect Trop D, 2012; 6 (12) (online): e1923-e1923. : http://dx.doi.org/10.1371/journal.pntd.0001923
• Nowak D, Klaumuenzer M, Hanfstein B, Mossner M, Nolte F, Nowak V, Oblaender J, Hecht A, Hutter G, Ogawa S, Kohlmann A, Haferlach C, Schlegelberger B, Braess J, Seifarth W, Fabarius A, Erben P, Saussele S, Muller MC, Reiter A, Buechner T, Weiss C, Hofmann WK, Lengfelder E: SNP array analysis of acute promyelocytic leukemia may be of prognostic relevance and identifies a potential high risk group with recurrent deletions on chromosomal subband 1q31.3. Gene Chromosome Canc, 2012; 51 (8): 756-767. : http://dx.doi.org/10.1002/gcc.21961
• Perera NC, Schilling O, Kittel H, Back W, Kremmer E, Jenne DE: NSP4, an elastase-related protease in human neutrophils with arginine specificity. P Natl Acad Sci Usa, 2012; 109 (16): 6229-6234. : http://dx.doi.org/10.1073/pnas.1200470109
• Pilzner C, Buhling F, Reinheckel T, Chwieralski C, Rathinasamy A, Lauenstein HD, Wex T, Welte T, Braun A, Groneberg DA: Allergic Airway Inflammation in Mice Deficient for the Antigen-Processing Protease Cathepsin E. Int Arch Allergy Imm, 2012; 159 (4): 367-383. : http://dx.doi.org/10.1159/000338288
• Qureshi SA, Koehler SM, Lin JD, Bird J, Garcia RM, Hecht AC: An evaluation of information on the internet about a new device: the cervical artificial disc replacement. Spine, 2012; 37 (10): 881-883. : http://dx.doi.org/10.1097/BRS.0b013e31823484fa
• Reifferscheid G, Maes HM, Allner B, Badurova J, Belkin S, Bluhm K, Brauer F, Bressling J, Domeneghetti S, Elad T, Fluckiger-Isler S, Grummt HJ, Gurtler R, Hecht A, Heringa MB, Hollert H, Huber S, Kramer M, Magdeburg A, Ratte HT, Sauerborn-Klobucar R, Sokolowski A, Soldan P, Smital T, Stalter D, Venier P, Ziemann C, Zipperle J, Buchinger S: International round-robin study on the Ames fluctuation test. Environ Mol Mutagen, 2012; 53 (3): 185-197. : http://dx.doi.org/10.1002/em.21677
• Reinheckel T, Peters C, Kruger A, Turk B, Vasiljeva O: Differential Impact of Cysteine Cathepsins on Genetic Mouse Models of De novo Carcinogenesis: Cathepsin B as Emerging Therapeutic Target. Front Pharmacol, 2012; 3 (online): 133-133. : http://dx.doi.org/10.3389/fphar.2012.00133
• Roring M, Brummer T: Aberrant B-Raf signaling in human cancer - 10 years from bench to bedside. Crit Rev Oncogenesis, 2012; 17 (1): 97-121.
• Roring M, Herr R, Fiala GJ, Heilmann K, Braun S, Eisenhardt AE, Halbach S, Capper D, von Deimling A, Schamel WW, Saunders DN, Brummer T: Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling. Embo J, 2012; 31 (11): 2629-2647. : http://dx.doi.org/10.1038/emboj.2012.100
• Schlatter R, Philippi N, Wangorsch G, Pick R, Sawodny O, Borner C, Timmer J, Ederer M, Dandekar T: Integration of Boolean models exemplified on hepatocyte signal transduction. Brief Bioinform, 2012; 13 (3): 365-376. : http://dx.doi.org/10.1093/bib/bbr065
• Schlatter R, Philippi N, Wangorsch G, Pick R, Sawodny O, Borner C, Timmer J, Ederer M, Dandekar T: Integration of Boolean models exemplified on hepatocyte signal transduction. Brief Bioinform, 2012; 13 (3): 365-376. : http://dx.doi.org/10.1093/bib/bbr065
• Schurigt U, Eilenstein R, Gajda M, Leipner C, Sevenich L, Reinheckel T, Peters C, Wiederanders B, Brauer R: Decreased arthritis severity in cathepsin L-deficient mice is attributed to an impaired T helper cell compartment. Inflamm Res, 2012; 61 (9): 1021-1029. : http://dx.doi.org/10.1007/s00011-012-0495-x
• Sifringer M, Bendix I, Borner C, Endesfelder S, von Haefen C, Kalb A, Holifanjaniaina S, Prager S, Schlager GW, Keller M, Jacotot E, Felderhoff-Mueser U: Prevention of neonatal oxygen-induced brain damage by reduction of intrinsic apoptosis. Cell Death Dis, 2012; 3: e250-e250. : http://dx.doi.org/10.1038/cddis.2011.133
• Sigglekow ND, Pangon L, Brummer T, Molloy M, Hawkins NJ, Ward RL, Musgrove EA, Kohonen-Corish MR: Mutated in colorectal cancer protein modulates the NFkappaB pathway. Anticancer Res, 2012; 32 (1): 73-79.
• Steenhuis P, Froemming J, Reinheckel T, Storch S: Proteolytic cleavage of the disease-related lysosomal membrane glycoprotein CLN7. Bba-mol Basis Dis, 2012; 1822 (10): 1617-1628. : http://dx.doi.org/10.1016/j.bbadis.2012.05.015
• Sun L, Wu Z, Hayashi Y, Peters C, Tsuda M, Inoue K, Nakanishi H: Microglial cathepsin B contributes to the initiation of peripheral inflammation-induced chronic pain. J Neurosci, 2012; 32 (33): 11330-11342. : http://dx.doi.org/10.1523/JNEUROSCI.0677-12.2012
• Unno T, Wakamori M, Koike M, Uchiyama Y, Ishikawa K, Kubota H, Yoshida T, Sasakawa H, Peters C, Mizusawa H, Watase K: Development of Purkinje cell degeneration in a knockin mouse model reveals lysosomal involvement in the pathogenesis of SCA6. P Natl Acad Sci Usa, 2012; 109 (43): 17693-17698. : http://dx.doi.org/10.1073/pnas.1212786109
• Vogel S, Raulf N, Bregenhorn S, Biniossek ML, Maurer U, Czabotar P, Borner C: Cytosolic Bax: does it require binding proteins to keep its pro-apoptotic activity in check? J Biol Chem, 2012; 287 (12): 9112-9127. : http://dx.doi.org/10.1074/jbc.M111.248906
• Vogel S, Raulf N, Bregenhorn S, Biniossek ML, Maurer U, Czabotar P, Borner C: Cytosolic Bax: does it require binding proteins to keep its pro-apoptotic activity in check? J Biol Chem, 2012; 287 (12): 9112-9127. : http://dx.doi.org/10.1074/jbc.M111.248906
• Wallmen B, Schrempp M, Hecht A: Intrinsic properties of Tcf1 and Tcf4 splice variants determine Nucleic Acids Res, 2012; 40 (19): 9455-9469. : http://dx.doi.org/10.1093/nar/gks690
• Wallmen B, Schrempp M, Hecht A: Intrinsic properties of Tcf1 and Tcf4 splice variants determine Nucleic Acids Res, 2012; 40 (19): 9455-9469. : http://dx.doi.org/10.1093/nar/gks690
• Wohlleber D, Kashkar H, Gartner K, Frings MK, Odenthal M, Hegenbarth S, Borner C, Arnold B, Hammerling G, Nieswandt B, van Rooijen N, Limmer A, Cederbrant K, Heikenwalder M, Pasparakis M, Protzer U, Dienes HP, Kurts C, Kronke M, Knolle PA: TNF-induced target cell killing by CTL activated through cross-presentation. Cell Rep, 2012; 2 (3): 478-487. : http://dx.doi.org/10.1016/j.celrep.2012.08.001
• Wohrle FU, Halbach S, Brummer T: The versatile role of Gab1 in the circulatory system. Circ J, 2012; 76 (8): 1838-1839.

• Leprivier G, Rufini A, Garcia-Saez AJ, Borner C, Rotblat B: 7th Tuscany Retreat on Cancer Research: genetic profiling, resistance mechanism and novel treatment concepts in cancer. Cell Death Differ, 2012; 19 (3): 546-548. : http://dx.doi.org/10.1038/cdd.2011.186
• Muller S, Dennemarker J, Reinheckel T: Specific functions of lysosomal proteases in endocytic and autophagic pathways. Bba-proteins Proteom, 2012; 1824 (1): 34-43. : http://dx.doi.org/10.1016/j.bbapap.2011.07.003

Besondere wissenschaftliche Aktivitäten

Abschlussarbeiten

• Britta Wallmen: Role of Tcf1 and Tcf4 splice variants in cell type-specific Wnt/β-catenin target gene expression, 2012.
• El Maadidi,Souhayla: Semliki Forest Virus uses alternative signaling pathways to induce apoptosis in the absence of Bax/Bak, 2012.
• Franziska Wöhrle: Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple Bcr-Abl inhibitors, 2012.
• Geißler, Andreas: Apoptosis induced by the Aspergillus fumigatus virulence factor gliotoxin, 2012.
• Jöckel,Lars: Role of serine proteases in inflammation and endoplasmic reticulum stress induced apoptosis, 2012.
• Michael Röring: B-Raf regulation by the dimer interface and activation loop phosphorylation, 2012.
• Raulf,Nina: Regulation of the survival factor Bcl-xLby binding partners and potential posttranslational modifications, 2012.
• Sá Ferreira,Karine: Analysis of Fas-mediated apoptosis in primary mouse hepatocytes by Systems Biology , 2012.