I am interested in how drugs work at the molecular level to either benefit or harm human health. This began with my graduate work at UC-Berkeley on drug metabolism in 1972 and has progressed through my professional career with extensive studies on the molecular pharmacology of the G-protein coupled receptors GPCRs) The GPCRs are a large “superfamily” of receptors with over 800 members in the human genome. They are the primary target for the majority of drugs in use today and are central to understanding how drugs work. From 1981-1989, I worked with Dr. Robert J. Lefkowitz at the Duke University Medical Center. During this time I studied the molecular pharmacology of the a2-adrenergic receptors, a member of the family of GPCRs. Like most GPCRs, until their molecular cloning the study of a2-receptors was exceptionally difficult due to their low natural abundance and the enormous purification needed for their isolation 100,000 fold) However, together with Dr. Brian Kobilka, we achieved the first purification and cloning of this receptor protein in 1987. This was among the very first GPCR to be cloned, preceded only by the cloning of the b2-adrenergic and M1-muscarinic receptors in 1986. In total I published 25 papers with Drs. Lefkowitz and/or Kobilka and in 2012 they both received the Nobel Prize in Chemistry for their seminal contributions to the field of GPCRs. In their Nobel lectures, they both acknowledged my contributions to this body of work. My laboratory at the University of Arizona is involved with studies of the molecular biology and signaling mechanisms of the prostanoid receptors, another subfamily of the GPCRs. Prostanoid receptors mediate the actions of the prostaglandins, which are hormonal substances that are involved with pain, fever and inflammation. Our studies of the prostanoid receptors led to the first cloning of the human EP2 receptor and to the cloning of the EP3 and FP receptor alternative splice variants. We have also characterized the activation of novel signaling pathways by these receptors involving phosphatidylinositol 3-kinase and elements of the Wnt signaling pathway. These findings have significance towards our understanding of cancer and other diseases.