The research in our group focuses on mechanisms by which signal transduction occurs within neurons, with particular emphasis placed on the cellular and molecular biology of receptor genes and their products. Our efforts are centered on a class of receptors that mediate the signaling actions of the purine ATP.

ATP is released by cells into the extracellular environment, where it can act upon transmembrane receptors to influence intracellular events. These purinergic receptors for ATP, based on structural and functional features, have been subdivided into two classes- the G-protein coupled receptors (P2Y) and the ligand-gated channels (P2X). It is the P2X receptor class that is the focus of our work. P2X receptors are non-selective cation channels that exhibit appreciable Ca2+ permeability and are present in most tissues of the body. These receptors are oligomeric proteins, and to date, seven different mammalian genes encoding P2X subunits have been identified. Although the various subunits exhibit a widespread distribution throughout the body, the lack of useful pharmacological tools has resulted in a poor understanding of the physiological roles that these receptors play.

Our lab is pursuing two investigative avenues into the function of these receptors. The first uses a molecular and biochemical approach to understand cellular function by identifying the structural domains of these proteins, whereas the second approach exploits the zebrafish (Danio) model system to gain an understanding of the physiological functions that these receptors are involved in.

Recently, we have identified and characterized, in a preliminary fashion, nine P2X subunit genes in the zebrafish. A number of these genes are expressed in the sensory neurons of the embryonic fish, and our current studies are focused on examining a)the composition of P2X receptors in the various subytpes of sensory neurons, b)their functional properties and c)their role in the development and function of the zebrafish sensory nervous system.