I am interested in the basic mechanisms of protein quality control systems at cellular membranes. I study how these systems select their substrates and aim to identify the cellular pathways regulated by them. These processes are important in pathologies related to cell stress, protein misfolding, and protein misregulation. Human illnesses linked to these problems include Parkinson’s disease, Alzheimer’s disease, and various cancers. My longer-term goal is to understand how changing conditions in cells target substrate proteins to these integral-membrane quality control systems.
Some of the questions that keep me up at night relate to the Endoplasmic Reticulum Associated Degradation (ERAD) system: How does ERAD recognize substrate proteins? What features of proteins make them substrates for selection? What role does the membrane play in the function of ERAD? What unknown proteins/pathways could be regulated by these systems? I am interested in setting up novel assays and using screening approaches to address these questions comprehensively. Insights from my approaches should allow screening for, and refinement of, therapeutics with value in a wide range of pathologies.