We are interested in the basic mechanisms of protein quality control systems at cellular membranes. We 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. Our longer-term goal is to understand how changing conditions in cells target substrate proteins to these integral-membrane quality control systems.
Basic mechanisms of endoplasmic reticulum associated degradation (ERAD)
Some of the questions that keep us up at night relate to the 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? We are interested in setting up novel assays and using screening approaches to address these questions comprehensively. Eventually, we hope to develop a screening platform to identify modulators of this quality control system. Insights from our approaches should allow screening for, and refinement of, therapeutics with value in a wide range of pathologies.
Protein quality control at organelle membranes
In this project, we are broadly interested in the function of integral membrane quality control systems (other than ERAD). We hope to address the following questions: How do unique integral membrane protein quality control systems function? Are the mechanics similar to ERAD? What proteins/pathways could be regulated by these systems?