Our goal is to understand the biology and enzymology of protein palmitoylation, a reversible posttranslational modification of proteins that impacts their localization, trafficking, and stability. Prominent in the nervous system, palmitoylation targets include receptors and their scaffold proteins, as well as signal transducers and their regulators. Like phosphorylation, palmitoylation is reversible and hence is regulated as well as regulatory. We hypothesize that palmitoylation represents a key dynamic regulatory mechanism for spatial and temporal control of cell signaling through its impact on protein localization.

A major focus of our work is the characterization of a recently discovered family of enzymes that palmitoylate proteins. Understanding the cell biology and enzymology of palmitoyltransferases will yield novel insights into how these enzymes can be manipulated for therapeutic benefit in cancer and neurological disorders. We study the enzymes in yeast and in mammalian organisms using molecular, genetic, and biochemical techniques. We are also designing assays for high throughput screens to identify inhibitors of palmitoyltransferases that can be used to probe the function of this versatile modification in vivo.