Investigations in my laboratory concentrate on biochemical and molecular mechanisms of signal transduction across the plasma membrane of differentiated mammalian cells. Because many endogenous regulators (hormones, neurotransmitters, growth factors and cytokines) as well as toxic xenobiotics act via alterations in cytosolic free calcium concentration ([Ca2+]i), a principal interest of the lab focuses on the modulation and functions of [Ca2+]i in normal and pathological states. Current emphasis is on neuropeptides. Studies included the molecular cloning of plasma membrane receptors, expression and function of cloned receptors in both mammalian cells and in Xenopus oocytes, biosynthesis, internalization, cycling and covalent modification of receptors that affect signal transduction, and identification of ligand binding domains and guanine nucleotide binding protein (G protein) coupling domains by site-specific mutations. Identification of G proteins and down-stream effector enzymes that generate second messenger molecules which regulate [Ca2+]i. These include the alpha and beta/gamma subunits of the heterotrimeric G proteins, inositol polyphosphates, cyclic ADP-ribose, and various protein kinases and phosphatases. Cell function is often monitored by means of specific protein biosynthesis (over minutes to hours) or secretion (over milliseconds to minutes).

We are also interested in the development and use of differentiated human and animal cell culture systems for investigations on the mechanisms of uptake, metabolism and cytotoxic actions of environmental chemicals, such as the marine agent palytoxin, and the cellular, biochemical and molecular actions of tumor promoters.