The Shi group develops super-resolution microscopy and advanced molecular profiling technologies to discover biomarkers that underlie neurodegenerative and mental health disorders. We create chemical and optical tools that power new spatial proteomics pipelines, 3D multiomics frameworks, and super-resolution deep-tissue imaging approaches, enabling deep and precise interrogation of single cells and their microenvironments in brains. These platforms reveal which proteins are altered in aging and disease, and how their interactions, signaling dynamics, and regulatory states vary across spatial contexts and disease stages—insights that are more direct to diagnosis than the transcriptome alone. By generating spatial proteomic datasets and super-resolution brain maps, we uncover protein biomarkers that mark early vulnerability, predict therapeutic response, and expose actionable intervention points. Ultimately, our work aims to identify and quantify molecular mechanisms that support precision medicine for neurodegenerative and mental health disorders.