We study the molecular machines and regulated protein assemblies that organize and remodel cellular membranes. Using mechanistic biochemistry, cell biology, and advanced imaging, we explore how these systems work, how they are regulated, and how they shape membrane trafficking and organelle function. Our current research focuses on lysosomal membrane stress, resilience, and repair. This program builds on longstanding work on ESCRT-driven membrane remodeling and AAA+ ATPase mechanisms in organelle function and disease.
Lysosomal membrane integrity
Lysosomes operate under unusually demanding chemical and physical conditions. Their membranes are challenged by oxidative stress, osmotic imbalance, protein and lipid accumulation, pathogens, and other damaging agents. Even limited disruption can compromise function and release harmful material into the cytoplasm. We study how cells detect lysosomal membrane stress, mount repair responses, and remove organelles when damage cannot be contained. A central question is what determines whether a stressed lysosome recovers or is ultimately eliminated via lysophagy.
ESCRT-driven membrane remodeling
ESCRT proteins form membrane-associated assemblies that drive remodeling events throughout the cell. Our laboratory has helped define the architecture and function of these assemblies. We are now asking what initiates ESCRT assembly on damaged lysosomal membranes, how membrane geometry and physical state shape the resulting structures, and how ESCRT activity is coordinated with other stress-response pathways. A key goal is to determine whether ESCRT assemblies stabilize stressed lysosomal membranes, seal small disruptions, remove compromised membrane by intralumenal budding, or serve different roles as damage and repair progress.
Membrane state and signaling
The physical and chemical state of a membrane can itself act as a signal. Differences in lipid composition, membrane organization, curvature, or tension can alter the recruitment and activity of proteins at the membrane surface. We study how cells detect such changes and translate them into local lipid signals, membrane remodeling, and communication between organelles. We are examining how phosphoinositide metabolism and lipid exchange are regulated at stressed lysosomal membranes and how these processes intersect with ESCRT activity and other homeostatic responses.
We are also extending these studies to membrane resilience in lysosomal storage disorders and neurodegeneration, repair responses to pulmonary epithelial injury, and cellular responses to membrane-damaging pathogens. The same mechanisms are relevant to intracellular delivery and endosomal escape, where therapeutic cargo must breach an endosomal membrane to reach the cytosol while evading or overcoming the cell’s repair machinery.