ZMB Member Hemmo Meyer

ZMB Member
Hemmo Meyer

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portrait photo of ZMB member Hemmo Meyer

Prof. Dr. Hemmo Meyer

Center of Medical Biotechnology (ZMB)
Faculty of Biology
University of Duisburg-Essen
Universitätsstr. 2
45141 Essen

Research Overview

Cellular homeostasis, proliferation and stress responses

Cells need to cope with a multitude of stress conditions that relentlessly inflict damage to its most vital components. This includes insults to the DNA that threatens genome stability, damage of proteins that can then form toxic aggregates, or injury of whole organelles such as mitochondria and lysosomes that releases harmful components. Cells have developed sophisticated molecular responses to these stresses that maintain protein homeostasis and organelle function, and ensure genomic stability. We are interested in deciphering these responses and uncover how they counteract stress-induced cell death and aging-related degeneration, or maintain cell proliferation.

The ubiquitin-proteasome system (UPS) is critically involved in cellular stress responses. Ubiquitination triggers degradation of damaged proteins by the proteasome, or removal of protein aggregates or hole organelles in the lysosome through autophagy. In addition, it regulates signalling pathways such as the DNA damage response and coordinates them with cell cycle progression.

A focus of our research has been the AAA+-type ATPase VCP/p97, which has emerged as a pivotal element of the UPS. It governs a variety of processes such as ER-associated degradation, ribosomal quality control, DNA damage responses as well as autophagy. Mutations in VCP/p97 in humans cause degenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), while pharmacological inhibition of VCP/p97 is considered as a strategy in cancer therapy. We have been working to reveal the molecular function of VCP/p97 and to understand how it cooperates with a host of accessory factors to trigger diverse stress responses in different compartments.

Cellular stress responses, proteostasis, ubiquitin-proteasome system, autophagy, lysosomal membrane permeabilization, lysophagy, mitophagy, DNA damage response, double strand break repair, cell cycle regulation.

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Selected Publications

    Journal articles

  • Gahlot, Pinki; Kravic, Bojana; Rota, Giulia; van den Boom, Johannes; Levantovsky, Sophie; Schulze, Nina; Maspero, Elena; Polo, Simona; Behrends, Christian; Meyer, Hemmo
    Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH
    In: Molecular Cell (2024) in press
  • van den Boom, Johannes; Marini, Guendalina; Meyer, Hemmo; Saibil, Helen R
    Structural basis of ubiquitin-independent PP1 complex disassembly by p97
    In: The EMBO Journal Vol. 42 (2023) Nr. 14, e113110
  • Kravić, Bojana; Bionda, Tihana; Siebert, Alexander; Gahlot, Pinki; Levantovsky, Sophie; Behrends, Christian; Meyer, Hemmo
    Ubiquitin profiling of lysophagy identifies actin stabilizer CNN2 as a target of VCP/p97 and uncovers a link to HSPB1
    In: Molecular Cell Vol. 82 (2022) Nr. 14, pp. 2633 - 2649.e7
  • Körver, Lisa; Papadopoulos, Chrisovalantis; Liu, Bin; Kravic, Bojana; Rota, Giulia; Brecht, Lukas; Veenendaal, Tineke; Polajnar, Mira; Blümke, Anika; Ehrmann, Michael; Klumperman, Judith; Jäättelä, Marja; Behrends, Christian; Meyer, Hemmo
    The ubiquitin-conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damage
    In: EMBO Reports (2019) pp. e48014
  • Weith, Matthias; Seiler, Jonas; van den Boom, Johannes; Kracht, Matthias; Hülsmann, Julia; Primorac, Ivana; Del Pino Garcia, Javier; Kaschani, Farnusch; Kaiser, Markus; Musacchio, Andrea; Bollen, Mathieu; Meyer, Hemmo
    Ubiquitin-Independent Disassembly by a p97 AAA-ATPase Complex Drives PP1 Holoenzyme Formation
    In: Molecular Cell Vol. 72 (2018) Nr. 4, pp. 766 - 777
  • van den Boom, Johannes; Meyer, Hemmo
    VCP/p97-Mediated Unfolding as a Principle in Protein Homeostasis and Signaling
    In: Molecular Cell Vol. 69 (2018) Nr. 2, pp. 182 - 194
  • Papadopoulos, Chrisovalantis; Meyer, Hemmo
    Detection and Clearance of Damaged Lysosomes by the Endo-Lysosomal Damage Response and Lysophagy
    In: Current Biology Vol. 27 (2017) Nr. 24, pp. R1330 - R1341
  • Papadopoulos, Chrisovalantis; Kirchner, Philipp; Bug, Monika; Grum, Daniel; Körver, Lisa; Schulze, Nina; Pöhler, Robert; Dressler, Alina; Fengler, Sven; Arhzaouy, Khalid; Lux, Vanda; Ehrmann, Michael; Weihl, Conrad C.; Meyer, Hemmo
    VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy
    In: The EMBO Journal Vol. 36 (2017) Nr. 2, pp. 135 - 150
  • van den Boom, Johannes; Wolf, Markus; Weimann, Lena; Schulze, Nina; Li, Fanghua; Kaschani, Farnusch; Riemer, Anne; Zierhut, Christian; Kaiser, Markus; Iliakis, George; Funabiki, Hironori; Meyer, Hemmo
    VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break Repair
    In: Molecular Cell Vol. 64 (2016) Nr. 1, pp. 189 - 198
  • Eiteneuer, Annika; Seiler, Jonas; Weith, Matthias; Beullens, Monique; Lesage, Bart; Krenn, Veronica; Musacchio, Andrea; Bollen, Mathieu; Meyer, Hemmo
    Inhibitor-3 ensures bipolar mitotic spindle attachment by limiting association of SDS22 with kinetochore-bound protein phosphatase-1
    In: The EMBO Journal Vol. 33 (2014) Nr. 22, pp. 2704 - 2720
  • Bebeacua, Cecilia; Förster, Andreas; McKeown, Ciarán; Meyer, Hemmo; Zhang, Xiaodong; Freemont, Paul S.
    Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 109 (2012) pp. 1098 - 1103.
  • Meyer, Hemmo; Bug, Monika; Bremer, Sebastian
    Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system
    In: Nature Cell Biology Vol. 14 (2012) Nr. 2, pp. 117 - 123
  • Ritz, Danilo; Vuk, Maja; Kirchner, Philipp; Bug, Monika; Schütz, Sabina; Hayer, Arnold; Bremer, Sebastian; Lusk, Caleb; Baloh, Robert H.; Lee, Houkeun; Glatter, Timo; Gstaiger, Matthias; Aebersold, Ruedi; Weihl, Conrad C.; Meyer, Hemmo
    Endolysosomal sorting of ubiquitylated caveolin-1 is regulated by VCP and UBXD1 and impaired by VCP disease mutations
    In: Nature Cell Biology Vol. 13 (2011) Nr. 9, pp. 1116 - 1123
  • Meerang, Mayura; Ritz, Danilo; Paliwal, Shreya; Garajova, Zuzana; Bosshard, Matthias; Mailand, Niels; Janscak, Pavel; Hübscher, Ulrich; Meyer, Hemmo; Ramadan, Kristijan
    The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks
    In: Nature Cell Biology Vol. 13 (2011) Nr. 11, pp. 1376 - 1382
  • Ramadan, Kristijan; Bruderer, Roland; Spiga, Fabio M.; Popp, Oliver; Baur, Tina; Gotta, Monica; Meyer, Hemmo
    Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin
    In: Nature Vol. 450 (2007) Nr. 7173, pp. 1258
  • Pye, Valerie E.; Beuron, Fabienne; Keetch, Catherine A.; McKeown, Ciaran; Robinson, Carol V.; Meyer, Hemmo; Zhang, Xiaodong; Freemont, Paul S.
    Structural insights into the p97-Ufd1-NpI4 complex
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 104 (2007) Nr. 2, pp. 467 - 472
  • Alam, Steven L; Sun, Ji; Payne, Marielle; Welch, Brett D; Blake, B Kelly; Davis, Darrell R; Meyer, Hemmo; Emr, Scott D; Sundquist, Wesley I
    Ubiquitin Interactions of NZF Zinc Fingers
    In: The EMBO Journal Vol. 23 (2004) Nr. 7, pp. 1411 - 1421
  • Meyer, Hemmo; Wang, Yanzhuang; Warren, Graham
    Direct binding of ubiquitin conjugates by the mammalian p97 adaptor complexes, p47 and Ufd1–Npl4
    In: The EMBO Journal Vol. 21 (2002) Nr. 21, pp. 5645 - 5652.
  • Hetzer, Martin; Meyer, Hemmo; Walther, Tobias C.; Bilbao-Cortes, Daniel; Warren, Graham; Mattaj, Iain W.
    Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly
    In: Nature Cell Biology Vol. 3 (2001) Nr. 12, pp. 1086 - 1091
  • Ye, Yihong; Meyer, Hemmo; Rapoport, Tom A.
    The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol
    In: Nature Vol. 414 (2001) pp. 652 - 656
  • Meyer, Hemmo; Shorter, James G.; Seemann, Joachim; Pappin, Darryl; Warren, Graham
    A complex of mammalian Ufd1 and Npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways
    In: The EMBO Journal Vol. 19 (2000) Nr. 10, pp. 2181 - 2192
  • Zhang, Xiaodong; Shaw, Anthony; Bates, Paul A.; Newman, Richard H.; Gowen, Brent; Orlova, Elena; Gorman, Michael A.; Kondo, Hisao; Dokurno, Pawel; Lally, John; Leonard, Gordon; Meyer, Hemmo; van Heel, Marin; Freemont, Paul S.
    Structure of the AAA ATPase p97
    In: Molecular Cell Vol. 6 (2000) Nr. 6, pp. 1473 - 1484