Dr. Philipp Berger



Paul Scherrer Institut
Forschungsstrasse 111
5232 Villigen PSI

Cellular engineering and microscopy

My group has a long-lasting interest in receptor signaling and trafficking. Initially, we analysed trafficking and signaling of Vascular Endothelial Growth Factor (VEGFR-2). We showed that different isoforms of VEGF-A lead to different recruitment of coreceptors leading to changes in intracellular trafficking and signaling (Ballmer-Hofer et al, 2011). In a large screen, we then identified then the TBC1D10 subfamily as a regulator of VEGFR2 signaling and angiogenesis (Xie et al., 2019). We then expanded to GPCRs, the biggest receptor family in the human genome that has also an important impact on drug development. To evaluate GPCR signalling, we switched to time-resolved recruitment of adaptor proteins (G proteins, arrestins, and GRKs) that initiate downstream cellular signalling of GPCRs. With these probes, we tested a set of bivalent oligoproline-based ligands for the Gastrin-Releasing Peptide Receptor (GRPR) and we observed different recruitment efficacies and potencies of our tested drugs (Romantini et al., 2021).

In order to measure trafficking and signaling of receptors, we developed several tools that are now widely used.

MultiLabel/ MultiPrime: This is a modular, cre/LoxP-based multigene expression system for mammalian cells. Expression plasmids can either be directly transfected or integrated in a baculovirus enabling also modification of mammalian cells (Kriz et al., 2010; Mansouri et al., 2016).

Squassh/ SquasshAnalyst: These tools allow the segmentation of fluorescence images and the quantification of colocalization between different channels (Rizk et al., 2014; Rizk et al., 2015). Manual and installation package are available here for download:

SquasshAnalyst manual.

GPCR activation assays: These assays are based on split nanoluciferase. They are available for several arrestins (Spillmann et al., 2020) and for GRK-2/ -3/ -5 (Romantini et al., 2021).


  • Loch RA, Wang H, Perálvarez-Marín A, Berger P, Nielsen H, Chroni A, et al.
    Cross interactions between Apolipoprotein E and amyloid proteins in neurodegenerative diseases
    Computational and Structural Biotechnology Journal. 2023; 21: 1189-1204. https://doi.org/10.1016/j.csbj.2023.01.022
  • Moazeni M, Berger P, Padeste C
    Polymer brush structures functionalized with molecular beacon for point-of-care diagnostics
    Micro and Nano Engineering. 2023; 19: 100184 (9 pp.). https://doi.org/10.1016/j.mne.2023.100184
  • Qin Y, Imobersteg S, Frank S, Blanc A, Chiorazzo T, Berger P, et al.
    Signaling network response to α-particle–targeted therapy with the 225Ac-labeled minigastrin analog 225Ac-PP-F11N reveals the radiosensitizing potential of histone deacetylase inhibitors
    Journal of Nuclear Medicine. 2023; 64(6): 873-879. https://doi.org/10.2967/jnumed.122.264597
  • Mortelmans T, Kazazis D, Padeste C, Berger P, Li X, Ekinci Y
    Poly(methyl methacrylate)-based nanofluidic device for rapid and multiplexed serological antibody detection of SARS-CoV-2
    ACS Applied Nano Materials. 2022; 5(1): 517-526. https://doi.org/10.1021/acsanm.1c03309
  • Nitzsche A, Pietilä R, Love DT, Testini C, Ninchoji T, Smith RO, et al.
    Paladin is a phosphoinositide phosphatase regulating endosomal VEGFR2 signalling and angiogenesis
    EMBO Reports. 2021; 22(2): e5021 (16 pp.). https://doi.org/10.15252/embr.202050218
  • Romantini N, Alam S, Dobitz S, Spillmann M, De Foresta M, Schibli R, et al.
    Exploring the signaling space of a GPCR using bivalent ligands with a rigid oligoproline backbone
    Proceedings of the National Academy of Sciences of the United States of America PNAS. 2021; 118(48): e2108776118 (8 pp.). https://doi.org/10.1073/pnas.2108776118
  • De Leo MG, Berger P, Mayer A
    WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms
    Autophagy. 2021; 17(11): 3644-3670. https://doi.org/10.1080/15548627.2021.1886830


  • Baculovirus-based genome editing in primary cells Mansouri M, Ehsaei Z, Taylor V, Berger P
    PLASMID 90, 5 (2017).
    DOI: 10.1016/j.plasmid.2017.01.003
  • Highly efficient baculovirus-mediated multigene delivery in primary cells Mansouri M, Bellon-Echeverria I, Rizk A, Ehsaei Z, Cianciolo Cosentino C, Silva Catarina S, Xie Y, Boyce Frederick M, Davis MWayne, Neuhauss Stephan CF, Taylor V, Ballmer-Hofer K, Berger I, Berger P
    NATURE COMMUNICATIONS 7, 11529 (2016).
    DOI: 10.1038/ncomms11529


  • Subcellular object quantification with Squassh3C and SquasshAnalyst Rizk A, Mansouri M, Ballmer-Hofer K, Berger P
    BIOTECHNIQUES 59, (2015).
    DOI: 10.2144/000114352
  • NRP1 Presented in trans to the Endothelium Arrests VEGFR2 Endocytosis, Preventing Angiogenic Signaling and Tumor Initiation Koch S, van Meeteren Laurens A, Morin E, Testini C, Weström S, Björkelund H, Le Jan S, Adler J, Berger P, Claesson-Welsh L
    DEVELOPMENTAL CELL 28, 633 (2014).
    DOI: 10.1016/j.devcel.2014.02.010
  • Segmentation and quantification of subcellular structures in fluorescence microscopy images using Squassh Rizk A, Paul G, Incardona P, Bugarski M, Mansouri M, Niemann A, Ziegler U, Berger P, Sbalzarini I
    NATURE PROTOCOLS 9, 586 (2014).
    DOI: 10.1038/nprot.2014.037
  • Strategies for multigene expression in eukaryotic cells Mansouri M, Berger P
    PLASMID 75, 12 (2014).
    DOI: 10.1016/j.plasmid.2014.07.001
  • Coordination of VEGF receptor trafficking and signaling by coreceptors Nakayama M, Berger P
    EXPERIMENTAL CELL RESEARCH 319, 1340 (2013).
    DOI: 10.1016/j.yexcr.2013.03.008
  • Integration of multiple expression cassettes into mammalian genomes in a single step Kriz A, Schmid K, Ballmer K, Berger P
    Protocol Exchange , (2011).
    DOI: 10.1038/protex.2011.249
  • Neuropilin-1 promotes VEGFR-2 trafficking through Rab11 vesicles thereby specifying signal output Ballmer-Hofer K, Andersson AE, Ratcliffe LE, Berger P
    BLOOD 118, 816 (2011).
    DOI: 10.1182/blood-2011-01-328773
  • The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling Berger P, Tersar K, Ballmer-Hofer K, Suter U
    DOI: 10.1111/j.1582-4934.2009.00967.x


  • A plasmid-based multigene expression system for mammalian cells Kriz A, Schmid K, Baumgartner N, Ziegler U, Berger I, Ballmer-Hofer K, Berger P
    NATURE COMMUNICATIONS 1, 120 (2010).
    DOI: 10.1038/ncomms1120
  • Automated unrestricted multigene recombineering for multiprotein complex production Bieniossek C, Nie Y, Frey D, Olieric N, Schaffitzel C, Collinson I, Romier C, Berger P, Richmond T, Steinmetz M, Berger I
    NATURE METHODS 6, 447 (2009).
    DOI: 10.1038/nmeth.1326
  • Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models Leal A, Huehne K, Bauer F, Sticht H, Berger P, Suter U, Morera B, Del Valle G, Lupski James R, Ekici A, Pasutto F, Endele S, Barrantes R, Berghoff C, Berghoff M, Neundörfer B, Heuss D, Dorn T, Young P, Santolin L, Uhlmann T, Meisterernst M, Sereda M, zu Horste G, Nave K, Reis A, Rautenstrauss B
    NEUROGENETICS 10, 275 (2009).
    DOI: 10.1007/s10048-009-0183-3
  • Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin Lebeurrier N, Launay S, Macrez R, Maubert E, Legros H, Leclerc A, Jamin SP, Picard JY, Marret S, Laudenbach V, Berger P, Sonderegger P, Ali C, di Clemente N, Vivien D
    JOURNAL OF CELL SCIENCE 121, 3357 (2008).
    DOI: 10.1242/jcs.031872
  • Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2 Tersar K, Boentert M, Berger P, Bonneick S, Wessig C, Toyka KV, Young P, Suter U
    HUMAN MOLECULAR GENETICS 16, 2991 (2007).
    DOI: 10.1093/hmg/ddm257
  • Multiprotein Expression Strategy for Structural Biology of Eukaryotic Complexes Fitzgerald Daniel J, Schaffitzel C, Berger P, Wellinger R, Bieniossek C, Richmond Timothy J, Berger I
    STRUCTURE 15, 275 (2007).
    DOI: 10.1016/j.str.2007.01.016
  • Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2 Berger P, Berger I, Schaffitzel C, Tersar K, Volkmer B, Suter U
    HUMAN MOLECULAR GENETICS 15, 569 (2006).
    DOI: 10.1093/hmg/ddi473
  • Pathomechanisms of mutant proteins in Charcot-Marie-Tooth disease Niemann A, Berger P, Suter U
    DOI: 10.1385/NMM:8:1:217
  • Protein complex expression by using multigene baculoviral vectors Fitzgerald D, Berger P, Schaffitzel C, Yamada K, Richmond T, Berger I
    NATURE METHODS 3, 1021 (2006).
    DOI: 10.1038/nmeth983
  • Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease) Berger P, Niemann A, Suter U
    GLIA 54, 243 (2006).
    DOI: 10.1002/glia.20386