Prof. Dr. Dirk Schlüter participates in RESIST research project B12.
| My Research Interest in RESIST |
Our research focus in RESIST is the characterization of the function of deubiquitinating enzymes (DUBs) in human bacterial infection, the evaluation of DUBs as novel drug targets and the development of small molecular compounds that selectively inhibit individual DUBs. The long-term goal is to contribute to the validation of new treatment strategies for bacterial infections, which target bacteria by antibiotic and simultaneously improve the anti-bacterial immune response by treatment with immunostimulatory DUB inhibitors. In the last years, we have shown that the DUBs CYLD, TNFAIP3 (A20) and OTUB1 are critical regulators of immune responses in experimental infectious and autoimmune disorders.
Built on this expertise and data, we will use innovative mouse models to carry out the structure/function analyses of DUBs in experimental Listeria monocytogenes and Staphylococcus aureus infections. We combine these infection models with studies on the function of DUBs and S. aureus in atopic dermatitis, since colonization of the skin with S. aureus aggravates atopic dermatitis and S. aureus frequently causes infections in AD patients (collaboration T. Werfel, L. Rösner; project A3, A4, B5, RESIST-Cohort). Our recent data show that individual DUBs are increasingly expressed in AD and attenuate the control of S. aureus by macrophages. Based on these data, we will develop DUB inhibitors that target specific domains of DUBs previously identified as relevant and test them in the aforementioned models.
Prof. Schlüter about his scientific work
Prof. Dr. Dirk Schlüter – Curriculum Vitae
Current Position
Undergraduate and Postgraduate Training
Academic and Research Posts
Other Scientific Roles
Awards and Prizes
10 Selected Publications
Mulas, F, Wang, X, Song, S, Nishanth, G, Yi, W, Brunn, A, Larsen, PK, Isermann, B, Kalinke, U, Barragan, A, Naumann, M, Deckert, M, Schlüter, D. The deubiquitinase OTUB1 augments NF-κB dependent immune responses of dendritic cells by stabilization of UBC13 in infection and inflammation. Cell Mol Immunol. 2020; DOI: 10.1038/s41423-020-0362-6
Wang X, Mulas F, Yi W, Brunn A, Nishanth G, Just S, Waisman A, Brück W, Deckert M, Schlüter D. The deubiquitinase OTUB1 inhibits central nervous system autoimmunity by preventing IFN-γ-induced hyperactivation of astrocytes through stabilization of SOCS1. EMBO J. 2019; e100947. DOI: 10.15252/embj.2018100947.
Nishanth G, Wolleschak D, Fahldieck C, Fischer T, Mullally A, Perner F, Schnöder TM, Just S, Heidel FH, Schlüter D. Gain of function in Jak2(V617F)-positive T-cells. Leukemia. 2017; 359(26):2778-89.
Dong W, Wang H, Shahzad K, Bock F, Al-Dabet MM, Ranjan S, Wolter J, Kohli S, Hoffmann J, Dhople VM, Zhu C, Lindquist JA, Esmon CT, Gröne E, Gröne HJ, Madhusudhan T, Mertens PR*, Schlüter D*, Isermann B*. Activated protein C ameliorates renal ischemia-reperfusion injury by restricting Y-box binding protein-1 ubiquitination. J Am Soc Nephrol. 2015; 26(11):2789-2799. * equal contribution
Nishanth G, Deckert M, Wex K, Massoumi R, Schweitzer K, Naumann M, Schlüter D. CYLD enhances severe listeriosis by impairing IL-6/STAT3-dependent fibrin production. PLOS Pathog. 2013; 9(6):e1003455.
Wang X, Deckert M, Xuan NT, Nishanth G, Just S, Waisman A, Naumann M, Schlüter D. Astrocytic A20 ameliorates experimental autoimmune encephalomyelitis by inhibiting NF-κB- and STAT1-dependent chemokine production in astrocytes. Acta Neuropathol. 2013; 126(5):711-724.
Haroon F, Drögemüller K, Händel U, Brunn A, Reinhold D, Mueller W, Trautwein C, Ernst M, Deckert M, Schlüter D. Gp130-dependent astrocytic survival is critical for the control of autoimmune central nervous system inflammation. J Immunol. 2011; 1868(11):6521-6531.
Drögemüller K, Helmuth U, Brunn A, Sakowicz-Burkiewicz M, Gutmann DH, Mueller W, Deckert M, Schlüter D. Astrocyte gp130 expression is critical for the control of Toxoplasma encephalitis. J Immunol. 2008; 181(4):2683-2693.
Sakowicz-Burkiewicz M, Nishanth G, Helmuth U, Drögemüller K, Busch DH, Utermöhlen O, Naumann M, Deckert M, Schlüter D. Proteinkinase C-θ critically regulates the activation and proliferation of pathogen-specific T cells in murine listeriosis. J Immunol. 2008; 180(8): 5601-5612.
Meissner M, Schlüter D, Soldati D. Role of Toxoplasma gondii myosin A in powering parasite gliding and host cell invasion. Science. 2002; 298(5594):837-840.
