Research Interests

We study the communication of innate immune cells with their environment and are 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 the receptor’s function remain enigmatic.

We recently discovered that GPR35 regulates the cell’s ion homeostasis, its metabolic and proliferative activity by interacting with the sodium-potassium pump.

Via specific, consciously designed and specific lipopeptides (‘pepducins’), we modulate GPR35 function and investigate whether its genetic dysfunction can be corrected chemically via pharmacological manipulation of the risk variant.

 

Key Publications

Pagano E, Elias JE, Schneditz G, Saveljeva S, Holland LM, Borrelli F, Karlsen TH, Kaser A, Kaneider NC. Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment. Gut. 2021 Mar 23:gutjnl-2020-323363. doi: 10.1136/gutjnl-2020-323363.

Cader MZ, de Almeida Rodrigues RP, West JA, Sewell GW, Md-Ibrahim MN, Reikine S, Sirago G, Unger LW, Iglesias-Romero AB, Ramshorn K, Haag LM, Saveljeva S, Ebel JF, Rosenstiel P, Kaneider NC, Lee JC, Lawley TD, Bradley A, Dougan G, Modis Y, Griffin JL, Kaser A. FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle. Cell. 2020 Jan 23;180(2):278-295.e23. doi: 10.1016/j.cell.2019.12.017.

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. GPR35 promotes glycolysis, proliferation, and oncogenic signaling by engaging with the sodium potassium pump. Sci Signal. 2019 Jan 1;12(562):eaau9048. doi: 10.1126/scisignal.aau9048.

Wieser V, Adolph TE, Enrich B, Kuliopulos A, Kaser A, Tilg H, Kaneider NC. Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors. Gut. 2017 May;66(5):930-938. doi: 10.1136/gutjnl-2015-310344. Epub 2016 Feb 8.

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 Jul;3(7):370-84. doi: 10.1002/emmm.201100145. Epub 2011 May 18.

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 Apr 17;137(2):332-43. doi: 10.1016/j.cell.2009.02.018.

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 Dec;8(12):1303-12. doi: 10.1038/ni1525.

Kaneider NC, Agarwal A, Leger AJ, Kuliopulos A. Reversing systemic inflammatory response syndrome with chemokine receptor pepducins. Nat Med. 2005 Jun;11(6):661-5. doi: 10.1038/nm1245.