Research
I study the communication of innate immune cells with their environment, and am particularly interested in G protein-coupled receptors (GPCRs) and the cellular consequences of their activation. The genetic locus of the orphan GPCR GPR35, and a coding variant of the receptor have been associated with risk for inflammatory bowel disease and primary sclerosing cholangitis. However, GPR35’s endogenous, relevant ligands and its function remain enigmatic. Via specific, consciously designed and specific lipopeptides I aim to modulate GPR35 function to reveal its biological function, and will investigate whether its genetic dysfunction can be corrected chemically via pharmacological manipulation of the risk variant.
Publications
GPR35 promotes glycolysis, proliferation, and oncogenic signaling by engaging with the sodium potassium pump. Schneditz G, Elias JE, Pagano E, Zaeem Cader M, Saveljeva S, Long K, Mukhopadhyay S, Arasteh M, Lawley TD, Dougan G, Bassett A, Karlsen TH, Kaser A, Kaneider NC. Sci Signal. 2019 Jan 1;12(562). pii: eaau9048. doi: 10.1126/scisignal.aau9048.
Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors. Wieser V, Adolph TE, Enrich B, Kuliopulos A, Kaser A, Tilg H, Kaneider NC. Gut. 2017 May;66(5):930-938. doi: 10.1136/gutjnl-2015-310344.
Niederreiter L, Fritz TM, Adolph TE, Krismer AM, Offner FA, Tschurtschenthaler M, Flak MB, Hosomi S, Tomczak MF, Kaneider NC, Sarcevic E, Kempster SL, Raine T, Esser D, Rosenstiel P, Kohno K, Iwawaki T, Tilg H, Blumberg RS, Kaser A.
ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells. J Exp Med. 2013;210:2041-56.
O'Callaghan K, Lee L, Nguyen N, Hsieh MY, Kaneider NC, Klein AK, Sprague K, Van Etten RA, Kuliopulos A, Covic L.
Targeting CXCR4 with cell-penetrating pepducins in lymphoma and lymphocytic leukemia. Blood 2012;119:1717-25.
Tressel SL, Kaneider NC, Kasuda S, Foley C, Koukos G, Austin K, Agarwal A, Covic L, Opal SM, Kuliopulos A.
A matrix metalloprotease-PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis.
EMBO Mol Med. 2011;3:370-84.
Trivedi V, Boire A, Tchernychev B, Kaneider NC, Leger AJ, O'Callaghan K, Covic L, Kuliopulos A. Platelet matrix metalloprotease-1 mediates thrombogenesis by activating PAR1 at a cryptic ligand site. Cell 2009;137:332-43.
Kaneider NC, Leger AJ, Agarwal A, Nguyen N, Perides G, Derian C, Covic L, Kuliopulos A. “Role reversal” for the receptor PAR1 in sepsis-induced vascular damage. Nat Immunol. 2007;8:1303-12.
Kaneider NC, Agarwal A, Leger AJ, Kuliopulos A. Reversing systemic inflammatory response syndrome with chemokine receptor pepducins, Nat Med, 2005;11:661-5.
Feistritzer C, Mosheimer BA, Tancevski I, Kaneider NC, Sturn DH, Patsch JR, Wiedermann CJ. Src tyrosine kinase-dependent migratory effects of antithrombin in leukocytes.
Exp Cell Res. 2005;305:214-20.
Kaneider NC, Kaser A, Dunzendorfer S, Tilg H, Patsch JR, Wiedermann CJ. Neurokinin-1 receptor interacts with PrP106–126-induced dendritic cell migration and maturation. J Neuroimmunology. 2005; 158:153-158
Kaneider NC, Lindner J, Feistritzer C, Sturn DH, Mosheimer BA, Djanani AM, Wiedermann CJ. The immune modulator FTY720 targets sphingosine-kinase-dependent migration of human monocytes in response to amyloid beta-protein and its precursor. FASEB J. 2004;18:1309-11.
Kaneider NC, Kaser A, Tilg H, Ricevuti G, Wiedermann CJ. CD40 ligand-dependent maturation of human monocyte-derived dendritic cells by activated platelets. Int J Immunopathol Pharmacol. 2003;16:225-31.
Kaser A, Kaser S, Kaneider NC, Enrich B, Wiedermann CJ, Tilg H. Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression. Blood. 2004;103:648-55.
Sturn DH, Kaneider NC, Feistritzer C, Djanani A, Fukudome K, Wiedermann CJ. Expression and function of the endothelial protein C receptor in human neutrophils. Blood. 2003;102:1499-505.
Kaneider NC, Kaser A, Dunzendorfer S, Tilg H, Wiedermann CJ. Sphingosine kinase-dependent migration of immature dendritic cells in response to neurotoxic prion protein fragment. J Virol. 2003;77:5535-9.
Kaneider NC, Egger P, Wiedermann FJ, Ritter M, Woll E, Wiedermann CJ. Involvment of cyclic adenosine monophosphate-dependent protein kinase A and pertussis toxin- sensitive G proteins in the migratory response of human CD14+ mononuclear cells to katacalcin. J Bone Miner Res. 2002;17:1872-82
Kaneider NC, Egger P, Dunzendorfer S, Wiedermann CJ. Rho-GTPase-dependent platelet-neutrophil interaction affected by HMG-CoA reductase inhibition with altered adenosine nucleotide release and function. Arterioscler Thromb Vasc Biol. 2002;22:1029-35.
Kaneider NC, Reinisch CM, Dunzendorfer S, Romisch J, Wiedermann CJ. Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes. J Cell Sci.;115:227-36.
