All cells must integrate and transduce multiple extracellular signals to achieve an appropriate functional response and phenotype. To perform these complex functions, cells form multiprotein complexes at the right time and with the correct spatial localization. These macromolecular structures integrate and transduce signals via modifications in their composition, by orchestrating subtle changes in the relationships between member proteins, and by being organized into larger supramolecular structures. We are interested in how multiprotein complexes, particularly those formed by transient, low affinity interactions, regulate critical cellular processes in inflammation and leukocyte differentiation. We study how macromolecular organization, distinct from functions of individual proteins, controls biological and biochemical functions. We combine molecular imaging approaches with biochemical and cell biology approaches. These include Fluorescence Lifetime Imaging Microscopy (FLIM), Stochastic Optical Reconstruction Microscopy (N-STORM), SILAC labeling, crosslinking, affinity chromatography and mass spectrometry. A goal of our work is to develop approaches to understanding macromolecular organization in cell biological systems and in vivo models. Disordered protein interactions, either structural or temporal, that lead to “disorganization” of multiprotein complexes may be the basis of many human diseases ranging from the initiation of inflammation in autoimmune disorders, to chronic neurodegenerative, cystic fibrosis, and kidney diseases. Ultimately, understanding the functions of these complexes will be key to understanding the interface between genomics and biochemical mechanisms of disease.