The Harel laboratory uses a combination of genetics, protein biochemistry and cell biology approaches, high resolution scanning electron microscopy (SEM) and correlative light-and-electron microscopy. Our recent work has revealed “plugged” pore channels as the cause of a rare genetic disorder in humans, caused by mutations in Nup214 and resulting in acute febrile encephalopathy and early death (Fichtman et al., Am. J. Hum. Genet. 2019). Additional projects are focused on a dysregulated cellular stress response in the context of neurodegeneration and nuclear envelope abnormalities.