K. Peter Hirth Chair of Cancer Biology and Professor of Cell and Developmental Biology; Investigator, Howard Hughes Medical Institute
University of California, Berkeley
Molecular & Cellular Biology
Recognized for: Fundamental discoveries related to ubiquitylation, a protein modification with ubiquitin that has emerged as a complex cellular language essential for information transfer and communication in nearly all organisms
Areas of Research Interest and Expertise: Mechanisms of Human Development and Disease; Ubiquitin-Dependent Signaling; Stem Cell Biology; Protein Degradation and Neurodegeneration
PhD, Max Planck Institute for Biochemistry, Germany Diploma, University of Bayreuth, Germany
Dr. Rape has identified new ubiquitin chain signals (first atypical chain, first branched chain), as well as their mechanism of assembly. This discovery provides a strong foundation for the “ubiquitin code” hypothesis, i.e. different types of ubiquitin conjugates can encode specific information in cells. Dr. Rape and his team discovered molecular mechanisms critical during early development: they revealed the mechanism of neural crest specification and collagen secretion which are both essential for craniofacial development, and affected in multiple developmental diseases and birth defects.
Dr. Rape has also revealed core principles of cell cycle regulation: how cells establish an order of events when they progress through the mitotic stage. He has developed novel therapeutic agents (molecular glues) as a novel approach to chemotherapy, showing that disease-causing proteins could be eliminated by targeting them to the ubiquitin machinery.
Systems biology of ubiquitin-dependent signaling: Ubiquitin signals are often very complex and depend on multiple enzymes for their assembly. Dr. Rape and his team are studying how multiple ubiquitylation enzymes and deubiquitylases cooperate to ensure specific assembly of ubiquitin signals.
Ubiquitin-dependent control of early human development: Dr. Rape and his team are performing this work both in human embryonic stem cells, as well as in metazoan organisms. In the long term, Dr. Rape wishes to extend this work to understanding of the interplay between distinct cell types during differentiation.
Neurodegeneration: The Rape Lab has discovered an important signal that protects neurons from the accumulation of toxic protein aggregates. They are now identifying novel components of neuronal protein quality control, working to understand their mechanisms of action and regulation.
“We are trying to dissect principles of information transfer in human cells that shed light on fundamental mechanisms of early human development and can be translated into novel therapies against developmental diseases and cancer.”