VCKD Members


Richard M Breyer Ph.D.

Department: Medicine


Prostaglandin E2 (PGE2) mediates a wide range of biological effects including anti-inflammatory effects,airway resistance in asthma, fertility and maintenance of vascular tone. The precise identity of the receptors which mediate these effects are unclear. The focus of Dr. Breyer's research is the characterization of the molecular mechanism of action of PGE2 and determination of the structure-function relationships of the PGE2 receptors. Dr. Breyer's group is currently investigating alterations in immune/inflammatory cells function in both allergic-asthma models as well as tumor models in the PGE2 EP2 receptor knockout. They are also investigating the physiology underlying multiple abnormalities observed in these animals, with the aim of determining the role of this receptor in other disease states including Alzheimer's disease and infertility. A second project in the laboratory involves using the EP3 receptors as a model system to study multiple signal transduction pathways activated by these G-protein coupled receptors. The prostaglandin EP3 receptor signals primarily through the inhibitory G-protein Gi, thereby decreasing intracellular cAMP levels, however preliminary studies have described a non-Gi coupled signal transduction pathway activated by the this receptor. Partial blockade of this novel signal transduction pathway with kinase inhibitors demonstrates that this pathway is transduced in part by a Ca++ dependent kinase pathway. Studies are underway to determine the downstream regulators which mediate this signal transduction pathway. In addition Dr. Breyer's lab has recently developed the technology for purifying milligram quantities of the recombinant G-protein coupled receptors. The goal of this project is to utilize this purified receptor protein to undertake biochemical characterization of the receptor protein, identify interacting proteins, and ultimately to determine the three dimensional structure of one of these receptors.

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