Cellular interactions within the tissue micro-environment form the basis of health and disease for all organisms. Exposure to nutrients, toxins, and neighboring cells triggers coordinated molecular responses that impact cellular function and metabolism in a beneficial, adaptive, or detrimental manner. Acquiring molecular information at cellular resolution is thus crucial for developing a comprehensive understanding of the biology of an organism. Matrix-assisted laser desorption/ionization (MALD) imaging mass spectrometry (IMS) addresses this need by combining the spatial fidelity of classical microscopy with the molecular specificity of a mass spectrometer. This presentation will highlight our work developing new, high-performance technologies for improving the spatial resolution, sensitivity, and specificity of MALDI IMS for metabolite, lipid, and protein mapping. This will include the utilization of novel MALDI methods and development efforts using high spatial resolution Q-TOF platforms to address the molecular complexity associated with direct tissue analysis. Further, I will describe recent advances in integrated, multimodal methods that correlate molecular signals to specific biological tissue features and cell types. These technologies will be demonstrated through various biomedical research applications that include the construction of molecular atlases and understanding the molecular drivers of normal aging and disease.
