Dr. rer. nat. Patricia Korn (geb. Verheugd)

Laboratory of mono-ADP-ribosylation in host-pathogen conflicts

Technician: 

Barbara Lippok
Tel.: 0241 80-88839
blippokukaachende

Bachelor and Master students:

Lea Hirschen, Bachelor student 

Alumni:

Frah Afzal, Bachelor student

Lena Daesler, Bachelor student

Johanna Eyll, Bachelor student

Anka Güldenpfennig, Bachelor student

Laura Krutt, Bachelor student

Ani Sabcheva, Bachelor student

Jan Schumacher, Bachelor student

Lukas Vogt, Bachelor student

Alexander Wolf, Bachelor student

Jessica Wündrich, Bachelor student

Salpy Baghdo, Master student

Jonas Fechner, Master student

Franziska Kaesler, Master student

Anne Lehmann, Master student

Jakob Neuser, Master student

Katharina Biaesch, PhD student

Sarah Knapp, PhD student

Sarah Krieg, PhD student

Maud Verheirstraeten, PhD 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). By regulating proteins and as lately been shown RNA, it likely impacts diverse cellular processes. This modification is intracellularly catalyzed by mono-ADP-ribosyltransferases diphtheria toxin-like (ARTDs), which are also known as PARP enzymes. 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 a reversible PTM. Hydrolysis is mediated 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) and SARS-CoV-2. We found that these viral macrodomains possess mono-ADP-ribosylhydrolase activity and thereby can regulate and control MARylation. Hydrolase activity seems essential for virus replication and immune evasion. In line with this we found PARP10 and PARP12 as being restrictive for virus replication.

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 and SARS-CoV-2 as a model.

Biaesch, K., Knapp, S., and Korn P. (2023). IFN-induced PARPs – Sensors of foreign nucleic acids? Pathogens 12(3), 457.

Krieg, S., Pott, F., Potthoff, L., Verheirstraeten, M., Bütepage, M., Golzmann, A., Lippok, B., Goffinet, C., Luscher, B., and Korn, P. (2023). Mono-ADP-ribosylation by ARTD10 restricts CHIKV replication by interfering with the proteolytic activity of nsP2. Cell Mol Life Sci 80(3):72.

Nizi, M.G., Maksimainen, M.M., Murthy, S., Massari, S., Alaviuhkola, J., Lippok, B.E., Sowa, S.T., Galera-Prat, A., Prunskaite-Hyyrylainen, R., Luscher, B., Korn, P., Lethio, L., and Tabarrini, O. (2022). Potent 2,3-dihydrophthalazine-1,4-dione derivatives as dual inhibitors for mono-ADP-ribosyltransferases PARP10 and PARP15. Eur J Med Chem 237, 114362.

Luscher, B., Verheirstraeten, M., Krieg, S., and Korn, P. (2022). Intracellular mono-ADP-ribosyltransferases at the host-virus interphase. Cell Mol Life Sci 79, 288.

Korn, P., Classen, A., Murthy, S., Guareschi, R., Maksimainen, M.M., Lippok, B.E., Galera-Prat, A., Sowa, S.T., Voigt, C., Rossetti, G., Lethio, L., Bolm, C., Luscher, B. (2021). Evaluation of 3- and 4-Phenoxybenzamides as Selective Inhibitors of the Mono-ADP-Ribosyltransferase PARP10. ChemistryOpen 10(10):939-948.

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.