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ZMB Member Hemmo Meyer

ZMB Member
Hemmo Meyer

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portrait photo of ZMB member Hemmo Meyer
© UDE

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.

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

Distribution of published plasmids through addgene.org.

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Press Releases

research image cells
© UDE/Pinki Gahlot
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uni-due.de | Presse release

Decomposition of Damaged Lysosomes New Signaling Pathway Decoded

[08.04.2024] Lysosomen sind die Recyclinghöfe in unseren Zellen: Die kugelförmigen Organellen bauen in ihrem Innern sowohl körpereigene als auch Fremdstoffe ab – zur anschließenden Weiterverwertung. Da ihr Inneres einen sauren pH-Wert aufweist, sind Schäden in der Membran, die die Lysosomen umschließt, gefährlich für Zellen. Wissenschaftler:innen der UDE haben einen neuen Signalweg identifiziert, der in diesem Fall zum Abbau des Lysosoms führt. Ihre Erkenntnisse, veröffentlicht in Molecular Cell, könnten dazu beitragen, neue Ansätze für die Behandlung neurodegenerativer Krankheiten zu entwickeln.

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image representing research
© UDE/Bojana Kravic
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uni-due.de | Presse release

Catabolic Processes in Cells Controlling the Danger Within

[06.07.2022] Trillions of cells in our body work non-stop to keep us alive. This generates waste that is decomposed in specialized cellular organs. But what happens if the cellular trash cans don't work? Researchers assume that this is the cause of numerous diseases. Biologists from UDE, together with a team from Munich, have now been able to show how cells protect themselves from their defective trash cans – because their contents are pretty serious.

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Selected Publications

    Journal articles

  • Kück, Anja; van den Boom, Johannes; Koska, Sandra; Ron, David; Meyer, Hemmo.
    Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 121 (2024) Nr. 36, e2408787121
  • 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) pp. 1556 - 1569.e10
  • Meyer, Hemmo; Kravic, Bojana.
    The Endo-Lysosomal Damage Response
    In: Annual Review of Biochemistry Vol. 93 (2024) Nr. 1, pp. 367 - 387
  • 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
  • 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
  • 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