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About Richard Deth

My research focus has been directed toward understanding the molecular basis of transmembrane signaling by G protein-coupled receptors. This includes the study of their structure using three-dimensional molecular graphics and modeling how the binding of various drugs causes a shift in their conformational state. We are particularly interested in the spontaneous activity exhibited by some receptors. In the case of D4 dopamine receptors we have characterized their conformation-dependent participation in the process of phospholipid methylation, a unique and novel mechanism of signaling. A cycle of D4 receptor-mediated phospholipid methylation requires resupply of a new methyl group from the single carbon folate pool, thereby linking activity of the D4 receptor to folate-dependent pathways of cellular metabolism. Different methylation states of the D4 receptor exhibit various degrees of spontaneous activity with regard to G protein coupling. Deficits in D4 receptor-mediated phospholipid methylation may contribute to the etiology of several neuropsychiatric disorders, including schizophrenia and depression.


Present Professor Emeritus of Pharmacology, Northeastern University

Research Interests