Ph.D. – Freie Universität Berlin, Germany, in Natural Sciences, summa cum laude, 2015
Diplom (B.Sc. + M.Sc.) – Technical University Dresden, Germany, in Chemistry, 2009
Pertussis toxin is the major virulence factor of Bordetella pertussis, or whooping cough, that binds to surface receptors of host cells, gets internalized and interferes with cell signaling by ADP-ribosylating Gi-proteins. Thereby, pertussis toxin suppresses the innate and acquired immune response of infected individuals, thereby promoting infection. While the systemic effects of pertussis toxin downstream signaling have been extensively studied, limited knowledge is available about the cellular binding and uptake of PT.
I aim to identify the glycosylated cell-surface binding partners responsible for the cellular uptake of pertussis toxin. For this, I am using advanced mass spectrometry, biochemistry, cell culture, chemoselective reactions as well as chemical biology techniques. Among those, I am using a photocrosslinking tool, a diazirine-modified N-acetyl mannosamine (ManNDAz) that cells metabolically incorporate in their glycans. Upon light irradiation, the resulting sialic acids on the endogenous glycans forms covalent bonds with nearby molecules, allowing the capture of binding events too weak to study by immunoprecipitation methods.
These findings will lead identify both protein and glycan components of cell-surface receptors of PT, enabling to develop therapeutic agents to perturb the cell entry of PT.
Hoffmann E, Streichert K, Nischan N, Seitz C, Brunner T, Schwagerus S, Hackenberger CPR, Rubini M. Stabilization of bacterially expressed Erythropoietin by single site-specific introduction of short branched PEG chains at naturally occurring glycosylation sites. Mol. Biosyst. (2016), published online 11 Jan 2016. Doi: 10.1039/C5MB00857C
Wands AM, Fujita A, McCombs JE, Cervin J, Dedic B, Rodriguez AC, Nischan N, Bond MR, Mettlen M, Trudgian DC, Lemoff A, Quiding-Jarbrink M, Gustavsson B, Steentoft C, Clausen H, Mirzaei H, Teneberg S, Yrlid U, Kohler JJ. Fucosylation and protein glycosylation create functional receptors for cholera toxin. eLIFE. (2015) Doi: 10.7554/eLife.09545
Pham ND, Fermaintt CS, Rodriguez AC, McCombs JE, Nischan N, Kohler JJ. Cellular metabolism of unnatural sialic acid precursors. Glycoconj. J. (2015), 32, 515-529.
Nischan N, Herce HD, Natale F, Bohlke N, Budisa N, Cardoso MC and Hackenberger CPR. Covalent Attachment of Cyclic TAT Peptides to GFP Results in Protein Delivery into Live Cells with Immediate Bioavailability. Ang. Chem. Int. Ed. (2015) 54: 1950-53.
Nischan N, Hackenberger CPR. Site-specific PEGylation of proteins: recent developments. J. Org. Chem. (2014) 79: 10727-33.
Tronnier A, Nischan N, Metz S, Wagenblast G, Münster I, Strassner T. Phosphorescent C∧C* Cyclometalated PtII Dibenzofuranyl-NHC Complexes – An Auxiliary Ligand Study. Berichte der deutschen chemischen Gesellschaft (2014), 256-264.
Nischan N, Chakrabarti A, Serwa RA, Bovee-Geurts PHM, Brock R and Hackenberger CPR. Stabilization of Peptides for Intracellular Applications by Phosphoramidate-Linked Polyethylene Glycol Chains. Ang. Chem. Int. Ed. (2013) 52: 11920-24.
Tronnier A, Nischan N, Strassner T. CC*-cyclometalated platinum(II) complexes with trifluoromethyl-acetylacetonate ligands - Synthesis and electronic effects. J. Organomet Chem. (2013), 730, 37-43.