Areas of specialty:
- Protein quality control and protein degradation
- Intracellular protein trafficking and targeting
- Structural basis of protein-protein and protein-drug interactions
- Macromolecular structure determination
We investigate a broad theme in cell biology: How cells regulate the quality and disposal of their constituent proteins. We are particularly interested in the quality control of proteins that are intrinsically prone to aggregation or misfolding, a molecular basis of pathology in many diseases including neurodegenerative disorders, cardiomyopathies and cystic fibrosis. We are also interested in how protein quality control processes oppose cellular transformation, oncogenesis and cancer by regulating the cellular levels of both pro- and anti-oncogenic signaling proteins. Much of our research focuses on determining how intracellular chaperones, which survey protein quality, cooperate with the ubiquitin-proteasome machinery to “decide” whether and how proteins are folded, preserved or degraded. A major current focus is CHIP (also called STUB1), a ubiquitinating protein that targets misfolded proteins bound to intracellular chaperones. We investigate how CHIP interacts with chaperones, with its protein targets, and with regulatory “cochaperones” that modulate CHIP’s activity.
A second research interest in the group is to investigate how chaperones and ubiquitinating proteins function in innate immune signaling pathways. While we study how such proteins interact with other components of innate immune pathways, we are particularly interested in how pathogenic organisms may evade innate immunity by subverting host cell chaperones and ubiquitinating proteins. Our current interest is to elucidate the mechanisms utilized by the nonstructural proteins (NS1 and NS2) of respiratory syncytial virus (RSV), which interact directly with several host ubiquitinating proteins to attenuate antiviral innate immune responses in infected cells.
Expertise:
- Intracellular Protein Quality Control
- Ubiquitination Mechanisms
- Structural Biology and Biophysical Methods
