Our research asks how the physical organization of the cell governs biological function and how its disruption drives human disease. We study biomolecular condensates—dynamic, membraneless compartments that concentrate biomolecules—and protein mobility as critical determinants of intracellular organization. Together, condensates and protein mobility regulate how proteins encounter substrates, coordinate biochemical reactions, and maintain cellular homeostasis. Our work has defined two mechanisms linking cellular organization to disease. We defined condensate dysfunction, a pathological state in which membraneless compartments lose integrity and fail to coordinate molecular processes. We also discovered proteolethargy, a reduction in protein mobility that prevents proteins from reaching their targets and disrupts cellular function. These mechanisms help explain how common stresses such as hyperglycemia, dyslipidemia, and inflammation impair cellular organization across diverse disease contexts.
Building on these discoveries, our laboratory is defining how condensate material properties and protein mobility shape health and disease. For example, we are investigating how metabolic state reshapes the chemical environment and material properties of biomolecular condensates, thereby disrupting the biochemical functions carried out within these compartments and driving cellular dysfunction in disease. In addition, we are mapping the protein mobility landscape of the proteome and identifying regulators that shape condensate chemistry and dynamics in disease. By positioning condensate material properties and protein mobility alongside abundance, activity, and localization as core dimensions of cellular regulation, this work defines a new axis of cell biology that governs cellular function and reveals therapeutic strategies to restore cellular organization in disease.
Research Projects
Current efforts in the laboratory are focused on
i) how metabolic state rewires condensate chemistry,
ii) protein mobility as a fundamental regulatory axis,
iii) restoring molecular motion in disease, and
iv) applying machine learning to understand cell biology in health and disease.