The Lawrence Lab investigates mechanisms of cellular stress response signaling, with a focus on elucidating the structural and cellular mechanisms that link altered stress signaling remodels to remodeled metabolism in the context of neurodegeneration. Work in the lab combines classic cell biology and biochemistry with insights from structural biological methods including cryo-Electron Microscopy (cryo-EM) and mass spectrometry to illuminate cellular decision making in response to stress with high resolution.
Building on prior discovery and characterization of signaling complexes within the mTOR and Integrated Stress Response (ISR) fields, the lab has built systems to map consequences of chronic stress signaling in neurodegenerative disease. Specifically, model chronic ISR signaling states are generated via CRISPR-engineering allosteric mutations in the ISR stress sensor eIF2B in vulnerable cell types including neurons and glia. We are using this platform to identify signaling mechanisms via which the ISR regulates mitochondrial function in the context of Parkinson’s Disease.