Studying the ubiquitin-proteasome system as a way to understand normal cellular function and to develop novel therapeutic approaches for diseases
Ubiquitin is a small protein that is used as a tag either to mark other intracellular proteins for destruction, or to alter their function. We undertake various approaches to uncover pathways and mechanisms involving ubiquitin, and convert this information into tools to study biology and interfere with disease. Our current focus is on elucidating the function of E3 ubiquitin ligases, the components of the ubiquitin system that are responsible for making ubiquitination a specific and controlled process. The relevance of E3 ligases is underscored by the fact that, when mutated, they can cause human diseases as illustrated by mutations of BRCA1 in breast cancer and of Parkin in Parkinson’s Disease.
Our laboratory utilizes molecular genetic, genomic, biochemistry, cell biology and molecular biology approaches with mammalian cells, mice and yeast. Our expertise is complemented by close collaborations on structural biology, bioinformatics, mass spectrometry, next-generation sequencing and fly models. We also develop high-throughput assays and use those to carry out screens aimed at identifying small molecules that can be used as research tools and can also be developed as pharmaceutical drug candidates. Finally, we collaborate with clinicians to translate our basic research findings into therapeutically relevant discoveries.