My laboratory focuses on three interrelated research projects: (1) functional characterization of the A2A adenosine receptor (A2AR), (2) physiological and pathological analyses of a calcium-inhibitable adenylyl cyclase (AC6) which is coupled to the A2AR, and (3) development of novel therapeutic treatment for Huntington』s disease (HD). A2AR is a major target of caffeine, the most widely used psychoactive substance. Stimulation of the A2AR activates at least two major cellular signaling cascades: adenylyl cyclase/cAMP/protein kinase A- and protein kinase C-mediated pathways. Novel interacting proteins of A2AR may also contribute to the action of A2AR. Given the importance of A2AR, we are actively investigating the regulation and function of A2AR in vivo. Our goal is to develop treatment(s) for neurodegenerative diseases (including HD) based on the functions and pharmacological properties of A2AR. We are also very interested in AC6, a cAMP production enzyme that is coupled to A2AR. Because AC6 has a long and unique N-terminal domain that binds to Snapin (a component of the SNARE complex which mediates neurotransmission and neurite outgrowth), AC6 might play complex roles in regulating calcium-cAMP interactions and neuronal activities. We are currently exploring the pathophysiological role of AC6 in vivo using genetic modified mouse models.