Stress signaling at the crossroads of development and disease

Hosts: Yogesh Kulathu and Alessio Ciulli

Venue: MSI Small Lecture Theatre , SLS

Abstract:

Human development can withstand mutational or environmental insults. Key to resilient cell fate specification are signaling pathways that detect stresses, such as nutrient limitation, oxidative damage, or toxin exposure, and in turn instigate reactions that alleviate or bypass such conditions. How stress responses safeguard tissue formation and homeostasis is 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 energy generation. 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 to prevent tissue degeneration. How stress response pathways are terminated is not known. I will describe our discovery of active and regulated stress response silencing that is tightly connected to human disease and suggest novel therapeutic approaches to correct aberrant stress signaling for therapeutic benefit against neurodegenerative disorders.

Bio:

Michael Rapé is an Investigator of the Howard Hughes Medical Institute, and the founding Head of the Molecular Therapeutics Division and Dr. K. Peter Hirth Chair of Cancer Biology at UC Berkeley.

Michael’s work revealed ubiquitin chain types, essential ubiquitylation enzymes and substrates, and ubiquitylation mechanisms essential for development and disease. He is best known for developing the “ubiquitin code” hypothesis and discovering a series of quality control machineries, including the role of VCP as a ubiquitin-dependent segregase, the reductive stress response, or quality control of protein complex composition. His work has been recognized with a Pew Scholar’s Award, a Vilcek Prize for Creative Promise given to the best immigrant in the Biomedical Sciences in the US, the National Blavatnik Award as the best biomedical scientist in the US under the age of 42, and an NIH Director’s New Innovator Award. Michael has recently been elected as foreign member of EMBO.

Michael co-founded Nurix, Zenith, and Lyterian Therapeutics, and he is an iPartner at The Column Group Ventures.