Jonathan Stamler's laboratory investigates the interaction of nitric oxide with proteins, in studies that are reshaping an understanding of NO biology and providing new insights into fundamental aspects of redox systems and globin evolution and function. Most cellular functions are sensitive to redox state. Redox regulation has been viewed as a simple on-off switch in proteins, corresponding to reduced and oxidized states. These responses are important signaling events that may also exert pathophysiological effects. We are interested in understanding the nature of redox-related signals, the mechanisms that control signal onset and duration at the molecular and organismal level, and the regulation by redox systems of complex physiological responses.
Nitric oxide is the prototypic redox-related signaling molecule.
Its chemical interactions with cysteines and transition metal centers have served as ubiquitous models within the field of redox biochemistry. NO targets include enzymes, G proteins, transcription factors, transporters, membrane receptors, respiratory proteins, and ion channels. It is the reactions of NO with hemoglobin, however, that have fundamentally shaped our understanding of NO biology. For example, the ability of NO to act as a heme ligand played a crucial role in its identification with endothelium-derived relaxing factor and in elucidation of its mechanism of action. More recently, we discovered that highly conserved cysteine residues in the b chains of human hemoglobin are major targets of nitrosylation both in vitro and in vivo .