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AG Krönke
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AG Krönke

Group Leader: Prof. Dr. Martin Krönke

Dr. Birgit Blissenbach (-84099 [Email protection active, please enable JavaScript.])
Daniela Grumme (-84099 )
Dr. Marialice Heider (-84090 )
Katja Krönke-Wiegmann (-84098 [Email protection active, please enable JavaScript.])
Maureen Menning (-84096 [Email protection active, please enable JavaScript.])
Dr. Bettina Tosetti (-84088 [Email protection active, please enable JavaScript.])

Filippo Betti
Dr. Alexandra Böcke
Dr. Susanne Brodesser
Anne Buning
Anna Catharina Carstens
Tomek Kwasny
Dr. Carola Pongratz

Research Topics:
TNF Signaling, NADPH oxidases, and Ceramide Generating Enzymes in Immunity to Infection and Cancer
TNF is a prominent pro-inflammtory cytokine that orchestrates immune reactions to infections and cancer. Most of TNF biological activities are mediated by the 55kDa membrane receptor TNF-R1. Among the many signaling patways emanating from of TNF-R1 we have a longstanding interest in the molecular pathways leading to the activation of sphingomyelinases, ceramide synthases, and NADPH oxidases (Nox).

In particular we currently pursue the following projects:

1) Individual roles of specific Nox enzymes in infection and cell death (Wiegmann, Yazdanpanah).

2) Individual roles of specific ceramide synthases and ceramides of distinct acyl chain lengths in TNF receptor signaling and ageing (Pongratz, Brodesser, Wiegmann).

3) Biological and biochemical characterization of neutral sphingomyelinase 3 (nSMase3) (Kwasny, Wiegmann)

4) Role of TNF-R1 adaptor protein FAN in cancer cell migration and metastasis (Böcke, Carstens, Buning)

The work is funded by the DFG (CRC 670, CRC 832, the cluster of excellence CECAD), and the Center of Molecular Medicine Cologne (CMMC).

Selected recent publications (2005 - date):
Seeger JM, Schmidt P, Brinkmann K, Hombach AA, Coutelle O, Zigrino P, Wagner-Stippich D, Mauch C, Abken H, Krönke M, Kashkar H. 2010. The proteasome inhibitor bortezomib sensitizes melanoma cells toward adoptive CTL attack. Cancer Res 70: 1825-34

Seeger JM, Brinkmann K, Yazdanpanah B, Haubert D, Pongratz C, Coutelle O, Krönke M, and Kashkar H. 2010. Elevated XIAP expression alone does not confer chemoresistance. Br J Cancer 102: 1717-23

Pongratz C, Yazdanpanah B, Kashkar H, lehmann ML, Kräusslich HG, and Krönke M. 2010. selection of potent non-toxic inhibitory sequences from randomized HIV-1 specific lentiviral short hairpin RNA library. PLoS One 5 (10): e13172

Bielig H, Velder J, Saiai A, Menning M, Meemboor S, Kalka-Moll W, Krönke
M, Schmalz HG, Kufer TA. Anti-inflammatory Arene-Chromium Complexes Acting as Specific Inhibitors of NOD2 Signalling. Chem Med Chem 2010 Dec 3;5(12):2065-71.

Yazdanpanah B, Wiegmann K, Tchikov V, Krut O, Pongratz C, Schramm M, Kleinridders A, Wunderlich T, Kashkar H, Utermöhlen O, Brüning JC, Schütze S, Krönke M. 2009 Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature 460: 1159-63.

Glowalla E, Tosetti B, Krönke M, Krut O. 2009. Proteomics-based identification of anchorless cell wall proteins as vaccine candidates against Staphylococcus aureus. Infect Immun 77: 2719-29.

Herz J, Pardo J, Kashkar H, Schramm M, Kuzmenkina E, Bos E, Wiegmann K, Wallich R, Peters PJ, Herzig S, Schmelzer E, Krönke M, Simon MM, Utermöhlen O. 2009. Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes. Nat Immunol 10: 761-768.

Schramm M, Herz J, Haas A, Krönke M, Utermöhlen O. 2008. Acid sphingomyelinase is required for efficient phago-lysosomal fusion. Cell Microbiol 10:1839-1853.

Popov A, Driesen J, Abdullah Z, Wickenhauser C, Beyer M, Debey-Pascher S, Saric T, Kummer S, Takikawa O, Domann E, Chakraborty T, Krönke M, Utermöhlen O, Schultze JL. 2008 Infection of myeloid dendritic cells with Listeria monocytogenes leads to the suppression of T cell function by multiple inhibitory mechanisms. J Immunol 181:4976-4988.

Haubert D, Gharib N, Rivero F, Wiegmann K, Hosel M, Krönke M, Kashkar H. 2007. PtdIns(4,5)P-restricted plasma membrane localization of FAN is involved in TNF-induced actin reorganization. EMBO J 26(14): 3308-3321

Abdullah Z, Saric T, Kashkar H, Baschuk N, Yazdanpanah B, Fleischmann BK, Hescheler J, Krönke M, Utermöhlen O. 2007. Serpin-6 expression protects embryonic stem cells from lysis by antigen-specific CTL. J Immunol 178: 3390-3399.

Kashkar H, Deggerich A, Seeger JM, Yazdanpanah B, Wiegmann K, Haubert D, Pongratz C, Krönke M. 2007. NF-kappaB-independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs. Blood 109: 3982-3988.

Schnaith A, Kashkar H, Leggio SA, Addicks K, Krönke M, Krut O. 2007. Staphylococcus aureus subvert autophagy for induction of caspase-independent host cell death. J Biol Chem 282: 2695-2706.

Popov A, Abdullah Z, Wickenhauser C, Saric T, Driesen J, Hanisch FG, Domann E, Raven EL, Dehus O, Hermann C, Eggle D, Debey S, Chakraborty T, Krönke M, Utermöhlen O, Schultze JL. 2006 Indoleamine 2,3-dioxygenase-expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection. J Clin Invest 116: 3160-3170.

Schneider-Brachert W, Tchikov V, Merkel O, Jakob M, Hallas C, Kruse ML, Groitl P, Lehn A, Hildt E, Held-Feindt J, Dobner T, Kabelitz D, Krönke M, Schutze S. 2006. Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism. J Clin Invest 116: 2901-2913.

Theisen DM, Pongratz C, Wiegmann K, Rivero F, Krut O, Krönke M. 2006. Trageting of HIV-1 Tat traffic and function by transduction-competent single chain antibodies. Vaccine 24: 3127-3136.

Krut O, Wiegmann K, Kashkar H, Yazdanpannah B, Krönke M. 2006. Novel tumor necorsis factor-responsive mammalian neutral sphingomyelinase-3 is a C-tail-anchored protein. J Biol Chem 281: 1384-1393.

Kashkar H, Seeger JM, Hombach A, Deggerich A, Yazdanpannah B, Utermoehlen O, Heimlich G, Abken H, Krönke M. 2006. XIAP targeting sensitizes Hodgkins Lymphoma cells for cytolytic T cell attack.  Blood 25: 3434-3440.

Kashkar H, Wiegmann K, Yazdanpannah B, Haubert D, Krönke M. 2005. Acid sphingomyelinase is indispensable for UV-induced bax conformational change at the mitochondrial membrane. J Biol Chem 280: 20804-20813.

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