Zhicheng Cui, PhD

Our research is dedicated to understanding how cellular signaling is organized and executed on membrane surfaces. By employing in-vitro and in-situ cryo-electron microscopy (cryo-EM), biochemistry, and cell biology, we aim to unravel how membrane surfaces govern protein function in physiologically relevant conditions.

Our core research focuses on three primary areas:

• Lysosomal Signaling: Far beyond its role in degradation, the lysosome functions as a critical sensing platform. We explore how the lysosomal membrane acts as a sophisticated command center where nutrient availability and growth factor signals are integrated to control mTORC1 activity. We utilize in vitro reconstitution and high-resolution cryo-EM to delineate the "logic" of these signaling complexes in their native-like states.
• Small GTPase Regulation: Small GTPases function as fundamental molecular switches that integrate environmental cues to coordinate cellular growth and metabolism. We investigate the spatiotemporal regulation of these switches, with an initial focus on the RAS family. By combining AI-driven structural biology with biochemical characterization, we aim to uncover the molecular basis of membrane-directed signaling and identify new avenues for therapeutic intervention.
• Membrane Remodeling: Biological membranes are dynamic, living interfaces. We seek to bridge the gap between basic mechanistic insights into membrane dynamics—driven by proteins that sense lipid identity and curvature—and their broader implications in vesicular traffic, organelle maintenance, and human disease.