Mechanisms and regulation of insulin receptor signal transduction.Protein-tyrosine phosphatases and the regulation of hormone action.Pathophysiology of obesity and Type 2 diabetes mellitus. Dr. Goldstein is one of the leading investigators defining the role of phosphotyrosine phosphatases (PTPs) is regulation of insulin signaling and insulin resistant states. He defined the major PTPs that regulate insulin receptor and substrate phosphorylation and characterized their alterations in rodent and human disease. He showed that PTP activity is controlled by reversible thiol oxidation and defined a unique pathway whereby the enzyme Nox4 mediates an insulin-induced oxidant signal via inhibition of PTPs in insulin-sensitive cells.