Prof. Dr. Evi Kostenis
Professor of Pharmaceutical Biology
Managing Director
Institute of Pharmaceutical Biology
Molecular, Cellular and Pharmacobiology Section
Research
Research pursued in our group deals with G protein-coupled receptors (GPCRs), the largest family of membrane proteins in the human genome, and their associated signaling networks.
We are particularly interested in the molecular mechanisms that GPCRs utilize to engage with their downstream effectors, such as but not limited to heterotrimeric G proteins and arrestins, and attempt to elucidate the cellular consequences originating therefrom. Among others, we explore the roles of GPCRs and their associated signaling pathways in health and disease paradigms using a wide variety of functional assay technologies.
Our signal transduction platform relies on state-of-the-art instrumentation for detection of fluorescence resonance energy transfer (FRET)- and bioluminescence resonance energy transfer (BRET). For example, we use FRET- and BRET-based biosensors to monitor protein conformational changes or protein-protein interactions in response to ligand-activated GPCRs. We also employ FRET- and BRET-based techniques to follow second messenger formation and intracellular Ca2+ mobilization, as well as label-free biosensor platforms based on detection of dynamic mass redistribution (DMR) and bio-impedance. With a Zeiss Apotome fluorescence microscope we follow the (sub-)cellular fate of receptors alone or together with their downstream effectors.
Essential to our overall endeavor is the use of well-validated cell models generated by CRISPR/Cas9 gene-editing as well as pharmacological tools to specifically disrupt the function of individual GPCRs and/or their downstream signaling networks.
With our cellular manipulations we aim to unravel general principles and basic mechanisms underlying GPCR and G protein function, and how these can be translated to and exploited for development of innovative therapies.
CV
| since 2006 | W3 Professor (Full Professor) for Pharmaceutical Biology at the University of Bonn |
| 2002 - 2006 | Head of in vitro Pharmacology, 7TM Pharma, Hørsholm, Denmark |
| 2001 - 2002 | Global GPCR project coordinator, Aventis Pharma Frankfurt, Germany |
| 1999 - 2001 | Group Leader in early drug discovery, cardiovascular disease group, Aventis Pharma Frankfurt, Germany |
| 1997 - 1999 | Visiting scientist with Dr. Jürgen Wess, National Institutes of Health, Bethesda, USA |
| 1995 - 1997 | Postdoctoral scientist as DAAD Fellow with Dr. Jürgen Wess, National Institutes of Health, Bethesda, USA |
| 1992 - 1995 | Dr. rer. nat. in Pharmacology & Toxicology, Subject: Allosteric modulation of muscarinic receptors, (summa cum laude), Prof. Dr. Klaus Mohr, University of Bonn, Germany |
| 1990 - 1992 | Full-time pharmacist in the Kurbad Apotheke, Bad Hersfeld, Germany, and freelance journalist for the Deutsche Apotheker Zeitung (DAZ) and the Pharmazeutische Zeitung (PZ) |
| 1990 | German licensure as pharmacist |
| 1985 - 1989 | Studies of Pharmacy, Philipps-University Marburg, Germany |
| 9/2022 | Co-Chair of the 4GPCRnet International Symposium, Leipzig, Germany |
| 9/2017 | Chair of the FOR2372 International GPCR Symposium, Bonn, Germany |
| 1/2016 - | Editorial Board member of The Journal of Biological Chemistry (JBC) |
| 3/2016 - 9/2022 |
Vice-Spokesperson, DFG-funded Research Training Group RTG1873 "Pharmacology of 7TM-receptors and downstream signaling pathways"; University of Bonn |
| 2/2016 - | Spokesperson, DFG-funded Research Unit FOR2372 "G protein signalling cascades: with new molecular probes and modulators towards novel pharmacological concepts"; University of Bonn |
| 4/2016 - | Member of the International advisory board of COMPARE (Center of membrane proteins and receptors, Universities of Birmingham & Nottingham) |
| 1/2014 | Editorial Board member of Molecular Pharmacology |
| 2023 | PHOENIX Pharmacy Science Prize 2023 in the Pharmaceutical Biology category |
| 2016 | Neuroallianz publication award "bronze" for the publication "The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules"; J Biol Chem. (2016) 291:705. doi: 10.1074/jbc.M115.683953. |
| 2013 | Neuroallianz publication award "gold" for the publication "Decoding signaling and function of the orphan G protein-coupled receptor GPR17 with a small-molecule agonist"; Sci Signal. (2013) 6:ra93. |
| 2013 | PHOENIX Pharmacy Science Prize 2013 in the Pharmaceutical Biology category |
| 2013 | Price for Inventors by the Ministry of North-Rhine Westfalia (Hochschul Wettbewerb Zukunft Erfinden NRW). 3rd Price: GPR17 agonists and Screening Assay |
| 2012 | Neuroallianz publication award "silver" for the publication entitled "A biased ligand for OXE-R uncouples Gα and Gβγ signalling within a heterotrimer" by Stefanie Blättermann et al.; Nat Chem. Biol. (2012) 8: 631-638 |
| 1997 | National Institutes of Health (NIH) Visiting Program award |
| 1995 | Research Fellowship of the German Academic Exchange Service (DAAD) |
Publications
How Carvedilol activates β2-adrenoceptors
Benkel T, Zimmermann M, Zeiner J, Bravo S, Merten N, Lim VJY, Matthees E, Drube J, Miess-Tanneberg E, Malan D, Szpakowska M, Monteleone S, Grimes J, Koszegi Z, Lanoiselée Y, O’Brien S, Pavlaki N, Dobberstein N, Inoue A, Nikolaev V, Calebiro D, Chevigné A, Sasse P, Schulz S, Hoffmann C, Kolb P, Waldhoer M, Simon K, Gomeza J, Kostenis E.
Nat Commun. (2022) 13:7109
Heterotrimeric G Protein Subunit Gαq Is a Master Switch for Gβγ-Mediated Calcium Mobilization by Gi-Coupled GPCRs
Pfeil EM, Brands J, Merten N, Vögtle T, Vescovo M, Rick U, Albrecht IM, Heycke N, Kawakami K, Ono Y, Ngako Kadji FM, Hiratsuka S, Aoki J, Häberlein F, Matthey M, Garg J, Hennen S, Jobin ML, Seier K, Calebiro D, Pfeifer A, Heinemann A, Wenzel D, König GM, Nieswandt B, Fleischmann BK, Inoue A, Simon K, Kostenis E.
Mol Cell. (2020) 80:940
Direct targeting of Gαq and Gα11 oncoproteins in cancer cells
Annala S, Feng X, Shridhar N, Eryilmaz F, Patt J, Yang J, Pfeil EM, Cervantes-Villagrana RD, Inoue A, Häberlein F, Slodczyk T, Reher R, Kehraus S, Monteleone S, Schrage R, Heycke N, Rick U, Engel S, Pfeifer A, Kolb P, König G, Bünemann M, Tüting T, Vázquez-Prado J, Gutkind JS, Gaffal E, Kostenis E.
Sci Signal. (2019) 12(573)
Publications
Arrestins as rheostats of GPCR signalling
Gutkind JS, Kostenis E.
Nat Rev Mol Cell Biol. (2018) 19:615
Lack of beta-arrestin signaling in the absence of active G proteins
Grundmann M, Merten N, Malfacini D, Inoue A, Preis P, Simon K, Rüttiger N, Ziegler N, Benkel T, Schmitt NK, Ishida S, Müller I, Reher R, Kawakami K, Inoue A, Rick U, Kühl T, Imhof D, Aoki J, König GM, Hoffmann C, Gomeza J, Wess J, Kostenis E.
Nat Commun. (2018) 9:341
The experimental power of FR900359 to study Gq-regulated biological processes
Schrage R, Schmitz AL, Gaffal E, Annala S, Kehraus S, Wenzel D, Büllesbach KM, Bald T, Inoue A, Shinjo Y, Galandrin S, Shridhar N, Hesse M, Grundmann M, Merten N, Charpentier TH, Martz M, Butcher AJ, Slodczyk T, Armando S, Effern M, Namkung Y, Jenkins L, Horn V, Stößel A, Tietze D, Imhof D, Galés C, Drewke C, Müller CE, Hölzel M, Milligan G, Tobin AB, Gomeza J, Dohlman HG, Sondek J, Harden TK, Bouvier M, Laporte SA, Aoki J, Fleischmann BK, Mohr K, König GM, Tüting T, Kostenis E.
Nat Commun. (2015) 6:10156
Decoding Signaling and Function of the Orphan G Protein-Coupled Receptor GPR17 with a Small Molecule Agonist
Hennen S, Wang H, Peters L, Merten N, Simon K, Spinrath A, Blättermann S, Akkari R, Schrage R, Schröder R, Schulz D, Vermeiren C, Zimmermann K, Kehraus S, Drewke C, Pfeifer A, König GM, Mohr K, Gillard M, Müller CE, Lu QR, Gomeza J, Kostenis E.
Sci Signal. (2013) 6(298).
A biased ligand for OXE-R uncouples Gα and Gβγ signaling within a heterotrimer
Blättermann S, Peters L, Otterbach PA, Bock A, Konya V, Weaver D, Gonzalez A, Schröder R, Tyagi R, Luschnig P, Gäb J, Hennen S, Ulven T, Pardo L, Mohr K, Gütschow M, Heinemann A, Kostenis E.
Nat Chem Biol. (2012) 8:631
Applying label-free dynamic mass redistribution technology to frame signaling of G protein-coupled receptors non-invasively in living cells
Schröder R, Schmidt J, Blättermann S, Peters L, Janssen N, Grundmann M, Seemann W, Kaufel D, Merten N, Drewke C, Gomeza J, Milligan G, Mohr K, Kostenis E.
Nat Protocols. (2011) 6:1748
Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements
Schröder R, Janssen N, Schmidt J, Kebig A, Merten N, Hennen S, Müller A, Blättermann S, Mohr-Andrä M, Zahn S, Wenzel J, Smith NJ, Gomeza J, Drewke C, Milligan G, Mohr K, Kostenis E
Nat Biotechnol. (2010) 28:943.
Complete list of publications
Press releases
Bonner Pharmaforscher erhalten Hightech-Gerät
Neuer Ansatz im Kampf gegen MS
Erfindungen für die Zukunft
Wie gestörte Zellkommunikation zu Krankheiten führt
Herz-Medikament kurbelt Reparatur von Neuronen an
Pflanzen-Wirkstoff bremst aggressiven Augenkrebs
Fisch soll bei der Suche nach MS-Medikamenten helfen
Evi Kostenis erhält den PHOENIX Pharmazie Wissenschaftspreis
Videos
Dr. GPCR - Podcast
2023 PHOENIX Pharmazie Wissenschaftspreis
