Our laboratory is focused on the development and application of proteomics technologies to provide new insight on biological function at the organelle, cellular and tissue levels. Our research has enabled new methods for quantitative interactome measurements and using our technologies we have begun exploration of concepts of systems structural biology. These studies reveal how protein conformations and protein-protein interactions change with phenotypic differences, during drug treatment, or other perturbations. Systems structural biology measurements are helping us identify how cancer cells can acquire chemoresistance to Irinotecan, Cisplatin, and other cancer drugs. These changes help improve understanding of functional differences in chemoresistant cancers that could enable development of future therapeutic strategies. In addition, we are also performing systems structural biology measurements on isolated mitochondria and heart tissue samples from mouse models of aging and heart failure. These studies have revealed differences in electron transport respirasome and synthasome supercomplex assemblies and other complexes that can improve understanding of mitochondrial maladaptive changes during heart failure. Knowledge of these changes can lead to future mitochondrial-targeting strategies to more effectively treat failing hearts.