Hemmo Meyer CV

CV Hemmo Meyer

portrait hemmo meyer

Prof. Dr. Hemmo Meyer

Faculty of Biology
Center of Medical Biotechnology (ZMB)
University of Duisburg-Essen

Scientific Career
Since 2009 Full Professor (W3) of Molecular Biology, University of Duisburg-Essen
2003 - 2009 Independent group leader, Institute of Biochemistry, ETH Zurich
1999 - 2003 Postdoctoral fellow, Yale University Medical School, New Haven, CT, USA
1997 - 1999 Postdoctoral fellow, ICRF (now Cancer Research UK), London, UK
Diplom (MSc) and PhD in Human Biology, University of Marburg, Germany
Functions and Appointments
Speaker of the CRC1430 (2021-)
Speaker of the RTG1431 (2013-2015)
Board member, Center of Medical Biotechnology (ZMB)
Faculty member of the International Max Planck Research School for Living Matter (IMPRS-LM)
Organizer, EMBO Workshop on AAA+ Proteins (2013)
Editorial Board member, Journal of Biological Chemistry (2009-2014)

Research Contribution

Our major contribution concerns fundamental molecular mechanisms and diverse cellular functions of the human AAA+ ATPase VCP/p97 and its host of cooperating partner proteins. Mutations in VCP/p97 cause a neuromuscular degenerative disease termed multisystem proteinopathy (MSP1), while, conversely, p97 is being explored as a cancer drug target.

In the past, we have identified the p97 ubiquitin adapter Ufd1-Npl4, thus directly linking p97 to the ubiquitin-proteasome system and establishing that different p97 adapters define alternative p97 complexes that are functionally distinct. We helped identify a key role of p97Ufd1-Npl4 in ER-associated degradation (ERAD), which is central for maintaining cellular protein homeostasis.

Moreover, we demonstrated that the same p97Ufd1-Npl4 complex extracts ubiquitin-tagged proteins from chromatin to regulate processes such as mitosis and DNA damage repair to ensure genomic stability. The power of this activity is well illustrated by our finding that p97 extracts sterically trapped Ku70/80 rings from DNA during DNA repair. In addition, we revealed that p97Ufd1-Npl4 controls central signaling events by targeting key cell cycle regulators such as CDC25A or the integrated stress response regulator PPP1R15B for degradation.

In parallel, we linked p97 to the endo-lysosomal system where it acts in complex with the UBXD1 and PLAA adapters. We revealed its critical involvement in the endo-lysosomal damage response (ELDR) in which it drives clearance of permeabilized lysosomes by lysophagy through extracting ubiquitinated proteins from the lysosomal membrane, and identified additional regulators that will help to further dissect the pathway. Notably, we and others showed that lysosome-related functions are specifically compromised in p97-associated disease pointing to new strategies for treatment.

Recently, we identified an unexpected ubiquitin-independent role of p97, which illustrates the functional plasticity of the system. We showed that p97 with a class of SEP-domain adapters (such as p37) regulates the biogenesis (rather than the degradation) of protein phosphatase-1 (PP1) holoenzymes in that it disassembles an intermediate PP1 complex. By reconstituting this process in vitro, we unambiguously demonstrated that disassembly involves ATP-driven unfolding and threading of one of the subunits through the central channel of the p97 hexamer.