My group’s interests overlap chemistry, biology and engineering, with an emphasis on the design and synthesis of materials that are biologically active and in applications of the materials to relevant problems in the biological and medical sciences. Much of our work uses self-assembled monolayers of alkanethiolates on gold to prepare model surfaces that are structurally defined, yet that can have complex compositions and present the ligands in spatially-organized patterns. We pioneered the design of ‘dynamic substrates’ that present ligands whose activities can be switched on and off in response to electrical or optical signals, particularly for studies that address the responses of adherent cells to changes in the extracellular matrix. These mimics of the extracellular matrix have led the way to the discovery of novel ligands that mediate cell adhesion. We have also developed robust surface chemistries for preparing biochip arrays and that are compatible with new analytical methods for analyzing the arrays. For example, we have developed the SAMDI method, which uses mass spectrometry to analyze the arrays, and we have extended this method to the first label-free approach for high throughput screening, to the functional annotation of recently sequenced genes and towards an understanding of the networks that regulate protein acetylation. Finally, a recent program is creating defined systems for exploring biochemical reactions to understand the role that localization of enzymes and substrates play in controlling reaction networks.