Alan Smrcka

Areas of Interest

G protein coupled receptors (GPCRs) form a large family of cell surface receptors responsible for triggering cellular responses to a variety of extracellular stimuli including drugs such as opiates, and hormones such as adrenaline, serotonin or acetylcholine. All GPCRs function through activation of trimeric G proteins located on the inner surface of the plasma membrane. Activated G proteins target ion channels or enzymes that produce second messengers with a variety of effects depending on the type of cell that is stimulated. Examples include regulation of synaptic transmission in the central nervous system, chemotaxis in the immune system, and vascular remodeling in the cardiovascular system. This family of receptors is an important target for pharmaceuticals and defects in GPCR systems are responsible for a number of diseases.Our laboratory focuses on analysis of the interactions between the G proteins and their protein targets at a molecular and structural level with the goal of understanding how these interactions lead to alterations in protein and cellular activities. Another goal is to connect the biochemical information about protein interaction interfaces to specific cellular physiologies. To this end we are developing antagonists of specific G protein interactions and using these tools to probe the functions of those interactions in living cells. This approach will help to define the roles of specific G protein interactions in physiological processes and as potential targets for therapeutic intervention in cardiovascular disease or cancer.