Leiterin der Arbeitsgruppe ADP-Ribosylierung
Tel.: 0241 80-80692
Laboratory of mono-ADP-ribosylation in host-pathogen conflicts
PhD students are members of the Biomedical Graduate School (BMGS) Aachen.
Maud Verheirstraeten, M.Sc.
Tel.: 0241 80-80277 (office); 0241 80-88848 (lab)
Bachelor and Master students:
Lena Daesler, Bachelor student
Johanna Eyll, Bachelor student
Frah Afzal, Bachelor student
Franziska Kaesler, Master student
Sarah Krieg, PhD student
Laura Krutt, Bachelor student, currently Master student at FH Aachen University of Applied Sciences
Jakob Neuser, Master student
Anka Güldenpfennig, Bachelor student, currently Master student at the University of Sheffield (UK, England)
Jonas Fechner, Master student
Anne Lehmann, Master student
My working group is interested in the function of mono-ADP-ribosylation (MARylation) in host-pathogen conflicts. MARylation is an emerging posttranslational modification (PTM) and thus regulates proteins and consequently diverse cellular processes. This modification is intracellularly catalyzed by mono-ADP-ribosyltransferases diphtheria toxin-like (ARTDs). Our latest research identified several mono-ARTDs as being responsive to type I interferons (IFNa and IFNb) and pathogen-associated molecular patterns (PAMPs) like LPS, implicating a function in innate immunity. MARylation is recognized and propagated or hydrolyzed by so-called macrodomains, structurally highly conserved protein folds. They can be found in all domains of life and in a subset of positive single strand RNA ((+)ssRNA) viruses, among them Chikungunya virus (CHIKV). We found that these viral macrodomains possess mono-ADP-ribosylhydrolase activity and thereby can regulate and control MARylation, supporting the idea of this PTM functioning in host-pathogen conflicts.
My team aims at deciphering the importance of a functional viral macrodomain for viral replication and host cell modulation. Further we aim at determining how mono-ARTDs and MARylation contribute to an innate immune response using CHIKV as a model.
Ekblad T., P. Verheugd, A.E. Lindgren, T. Nyman, M. Elofsson, H. Schüler. Identification of Poly(ADP-ribose) Polymerase macrodomain inhibitors using an AlphaScreen protocol. SLAS Discov. 2018 Apr;23(4):353-362.
Eckei L., S. Krieg, M. Bütepage, A. Lehmann, A. Gross, B. Lippok, A.R. Grimm, B.M. Kümmerer, G. Rossetti, B. Lüscher, P. Verheugd. The conserved macrodomains of nonstructural proteins of Chikungunya virus and other pathogenic positive strand RNA viruses function as mono-ADP-ribosyltransferases. Sci Rep. 2017 Feb 2;7:41746.
Venkannagari H., P. Verheugd, J. Kolvunen, T. Haikarainen, E. Obaji, Y. Ashok, M. Narwal, T. Pihlajaniemi, B. Lüscher, L. Lethiö. Small molecule chemical probe rescues cells from mono-ADP-ribosyltransferase ARTD10/PARP10-induced apoptosis and sensitizes cancer cells to DNA damage. Cell Chem Biol. 2016 Sep 22. pii:S2451-9456(16)30295-1.
Verheugd P., M. Bütepage, L. Eckei, B. Lüscher. Players in ADP-ribosylation. Curr Protein Pept Sci. 2016 Apr 19.
Bütepage M., L. Eckei, P. Verheugd*, B. Lüscher*. Mono-ADP-ribosylation in signaling and disease. Cells, 2015 Sep 25;4(4):569-95.
Verheugd P., L. Milke, N. Herzog, K. L. H. Feijs, A. H. Forst, E. Kremmer, H. Kleine, B. Lüscher. Regulation of NF-κB signaling by the mono-ADP-ribosyltransferase ARTD10. Nat Commun. 2013;4:1683.