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 characterize the expression profile of the 100 identified DUBs in human implant-associated bacterial infections and, in parallel, in representative mouse models of these disorders. We will use the identified DUB profile to select candidate DUBs as drug targets and to verify the functional importance of these DUBs in experimental model systems. The final aim is to develop small molecule inhibitors for identified DUBs and to establish their efficacy as an adjunct treatment in combination with antibiotics in implant- associated infections.
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.