Professor Michael Rapé – University of California Berkeley

09/02/2024 11:00 am - 09/02/2024 12:00 pm
Davis Auditorium

WEHI Special UbS Seminar hosted by Professor David Komander

Professor Michael Rapé
Investigator, Howard Hughes Medical Institute
Professor and Head, Division of Molecular Therapeutics
Dr K. Peter Hirth Chair of Cancer Biology
University of California Berkeley, USA

Stress signaling at the crossroads of development and disease


Davis Auditorium

Join via TEAMS

Including Q&A session


Human development can withstand many mutational or environmental insults. Key to robust cell fate specification are signaling pathways that detect various stresses, such as nutrient limitation, oxidative damage, or toxin exposure, and in turn instigate reactions that either alleviate or bypass such conditions. How stress responses safeguard tissue formation and homeostasis is still poorly understood. We have recently discovered several stress responses with important roles in cell differentiation, including dimerization quality control, aggregate clearance, or the reductive stress response. These pathways ensure cell homeostasis by controlling processes as diverse as complex formation, protein aggregation, and mitochondrial activity. However, while transient stress signaling provides cells with time to repair damage, these pathways must also be turned off at the right time and place. How stress response pathways are terminated is not known. Here, I will describe our discovery of a large E3 ligase, the SIFI complex, with inactivates mitochondrial stress signaling to ensure cellular homeostasis. Mutations in SIFI subunits cause neurodegenerative disease, indicating that stress response silencing is an important process to ensure tissue homeostasis.


Michael Rapé received his PhD at the Max-Planck Institute of Biochemistry in Germany, before he joined Marc Kirschner’s lab at Harvard Medical School for his postdoctoral studies. In 2006, Michael joined the Department of Molecular and Cell Biology at the University of California at Berkeley, where he is currently Head of the Division of Molecular Therapeutics and the Dr K. Peter Hirth Chair of Cancer Biology. Michael is also an Investigator of the Howard Hughes Medical Institute. Michael’s lab uncovers molecular mechanisms of cell fate determination, using posttranslational modification with ubiquitin as their starting point. This work revealed new ubiquitin chain types, essential ubiquitylation enzymes and substrates, as well as mechanisms of ubiquitylation that are essential for human development and disease. His work has been recognized with a Pew Scholar’s Award, the Vilcek Prize for Creative Promise, the National Blavatnik Award, and an NIH Director’s New Innovator Award. Michael has recently been elected as foreign member of EMBO. His work led to the first prospective development of a molecular glues targeting E3 ligases, which helped in opening up the ubiquitin system for drug discovery. To advance ubiquitin-focused approaches in drug discovery, Michael co-founded Nurix Therapeutics, Zenith Therapeutics, and Lyterian Therapeutics. Michael is also an iPartner at The Column Group Ventures.

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