Decoding the “NPC (nuclear pore complex) code”
The nuclear pore complex (NPC) is the primary gateway for macromolecular traffic between the nucleus and cytoplasm. Although traditionally viewed as a relatively static transport channel, recent findings suggest that NPCs can differ markedly in their number per nucleus, post-translational modifications, and protein composition depending on cell type, developmental stage, or disease state. We study how these compositional and regulatory variations establish distinct NPC functional states—an idea we refer to as the “NPC code”—using a combination of quantitative and super-resolution microscopy, functional assays in Drosophila and mammalian cells, and in vitro biochemistry. Ultimately, our goal is to define the broader principle that the NPC itself acts as a key regulatory node in cellular function and physiology.
Integrating and manipulating signals for nuclear-cytoplasmic protein localization
The spatial organization of proteins between the nucleus and cytoplasm is dynamically regulated in a cellular context-dependent manner. We are interested in understanding how different nuclear localization signals (NLSs) and nuclear export signals (NESs) function, both in canonical and non-canonical ways, and how they converge to control where proteins localize and when. Our work also involves developing new tools to manipulate nuclear-cytoplasmic transport pathways in living cells, enabling us to probe causality and reprogram spatial protein organization with temporal precision.
Nuclear-cytoplasmic transport in disease states
Defects in nuclear-cytoplasmic transport have been increasingly implicated in a range of human diseases, including cancer, viral infection, and neurodegeneration. Taking advantage of Drosophila disease models, we aim to understand how transport dynamics and machinery are disrupted in specific pathological contexts and to uncover potential new avenues for therapeutic intervention.