Profile

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.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice. Ceddia RP, Lee D, Maulis MF, Carboneau BA, Threadgill DW, Poffenberger G, Milne G, Boyd KL, Powers AC, McGuinness OP, Gannon M, Breyer RM (2016) Endocrinology 157(1): 220-32
    › Primary publication · 26485614 (PubMed) · PMC4701878 (PubMed Central)
  2. EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling. Lu A, Zuo C, He Y, Chen G, Piao L, Zhang J, Xiao B, Shen Y, Tang J, Kong D, Alberti S, Chen D, Zuo S, Zhang Q, Yan S, Fei X, Yuan F, Zhou B, Duan S, Yu Y, Lazarus M, Su Y, Breyer RM, Funk CD, Yu Y (2015) J Clin Invest 125(3): 1228-42
    › Primary publication · 25664856 (PubMed) · PMC4362262 (PubMed Central)
  3. Cyclooxygenase-2-derived prostaglandin E₂ promotes injury-induced vascular neointimal hyperplasia through the E-prostanoid 3 receptor. Zhang J, Zou F, Tang J, Zhang Q, Gong Y, Wang Q, Shen Y, Xiong L, Breyer RM, Lazarus M, Funk CD, Yu Y (2013) Circ Res 113(2): 104-14
    › Primary publication · 23595951 (PubMed) · PMC4219358 (PubMed Central)
  4. Differential stem- and progenitor-cell trafficking by prostaglandin E2. Hoggatt J, Mohammad KS, Singh P, Hoggatt AF, Chitteti BR, Speth JM, Hu P, Poteat BA, Stilger KN, Ferraro F, Silberstein L, Wong FK, Farag SS, Czader M, Milne GL, Breyer RM, Serezani CH, Scadden DT, Guise TA, Srour EF, Pelus LM (2013) Nature 495(7441): 365-9
    › Primary publication · 23485965 (PubMed) · PMC3606692 (PubMed Central)
  5. Correction to CHOBIMALT: A Cholesterol-Based Detergent. Howell SC, Fraser NJ, Mittal R, Huang L, Travis B, Breyer RM, Sanders CR (2013) Biochemistry 52(2): 445
    › Primary publication · 23289860 (PubMed) · PMC3560918 (PubMed Central)
  6. Development of an in vivo active, dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere. Downey JD, Saleh SA, Bridges TM, Morrison RD, Daniels JS, Lindsley CW, Breyer RM (2013) Bioorg Med Chem Lett 23(1): 37-41
    › Primary publication · 23218714 (PubMed) · PMC3534858 (PubMed Central)
  7. Extracellular loop II modulates GTP sensitivity of the prostaglandin EP3 receptor. Natarajan C, Hata AN, Hamm HE, Zent R, Breyer RM (2013) Mol Pharmacol 83(1): 206-16
    › Primary publication · 23087260 (PubMed) · PMC3533480 (PubMed Central)
  8. Inactivation of the E-prostanoid 3 receptor attenuates the angiotensin II pressor response via decreasing arterial contractility. Chen L, Miao Y, Zhang Y, Dou D, Liu L, Tian X, Yang G, Pu D, Zhang X, Kang J, Gao Y, Wang S, Breyer MD, Wang N, Zhu Y, Huang Y, Breyer RM, Guan Y (2012) Arterioscler Thromb Vasc Biol 32(12): 3024-32
    › Primary publication · 23065824 (PubMed) · PMC3565847 (PubMed Central)
  9. EP1 disruption attenuates end-organ damage in a mouse model of hypertension. Bartlett CS, Boyd KL, Harris RC, Zent R, Breyer RM (2012) Hypertension 60(5): 1184-91
    › Primary publication · 23006735 (PubMed) · PMC3478772 (PubMed Central)
  10. Goodpasture antigen-binding protein (GPBP) directs myofibril formation: identification of intracellular downstream effector 130-kDa GPBP-interacting protein (GIP130). Revert-Ros F, López-Pascual E, Granero-Moltó F, Macías J, Breyer R, Zent R, Hudson BG, Saadeddin A, Revert F, Blasco R, Navarro C, Burks D, Saus J (2011) J Biol Chem 286(40): 35030-43
    › Primary publication · 21832087 (PubMed) · PMC3186396 (PubMed Central)
  11. Evidence for the presence of a critical disulfide bond in the mouse EP3γ receptor. Downey JD, Sanders CR, Breyer RM (2011) Prostaglandins Other Lipid Mediat 94(1-2): 53-8
    › Primary publication · 21236356 (PubMed) · PMC3065360 (PubMed Central)
  12. Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting. Guan Y, Zhang Y, Wu J, Qi Z, Yang G, Dou D, Gao Y, Chen L, Zhang X, Davis LS, Wei M, Fan X, Carmosino M, Hao C, Imig JD, Breyer RM, Breyer MD (2007) J Clin Invest 117(9): 2496-505
    › Primary publication · 17710229 (PubMed) · PMC1940235 (PubMed Central)
  13. Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. Hata AN, Lybrand TP, Breyer RM (2005) J Biol Chem 280(37): 32442-51
    › Primary publication · 16030019 (PubMed)
  14. Solution NMR spectroscopy of the human vasopressin V2 receptor, a G protein-coupled receptor. Tian C, Breyer RM, Kim HJ, Karra MD, Friedman DB, Karpay A, Sanders CR (2005) J Am Chem Soc 127(22): 8010-1
    › Primary publication · 15926814 (PubMed)
  15. Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Hata AN, Lybrand TP, Marnett LJ, Breyer RM (2005) Mol Pharmacol 67(3): 640-7
    › Primary publication · 15563582 (PubMed)
  16. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Hata AN, Breyer RM (2004) Pharmacol Ther 103(2): 147-66
    › Primary publication · 15369681 (PubMed)
  17. Expression and molecular pharmacology of the mouse CRTH2 receptor. Hata AN, Zent R, Breyer MD, Breyer RM (2003) J Pharmacol Exp Ther 306(2): 463-70
    › Primary publication · 12721327 (PubMed)
  18. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. Yang L, Yamagata N, Yadav R, Brandon S, Courtney RL, Morrow JD, Shyr Y, Boothby M, Joyce S, Carbone DP, Breyer RM (2003) J Clin Invest 111(5): 727-35
    › Primary publication · 12618527 (PubMed) · PMC151895 (PubMed Central)
  19. Contribution of prostaglandin EP(2) receptors to renal microvascular reactivity in mice. Imig JD, Breyer MD, Breyer RM (2002) Am J Physiol Renal Physiol 283(3): F415-22
    › Primary publication · 12167591 (PubMed)
  20. Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. Kennedy CR, Zhang Y, Brandon S, Guan Y, Coffee K, Funk CD, Magnuson MA, Oates JA, Breyer MD, Breyer RM (1999) Nat Med 5(2): 217-20
    › Primary publication · 9930871 (PubMed)
  21. The second extracellular loop of the prostaglandin EP3 receptor is an essential determinant of ligand selectivity. Audoly L, Breyer RM (1997) J Biol Chem 272(21): 13475-8
    › Primary publication · 9153190 (PubMed)
  22. Differential localization of prostaglandin E receptor subtypes in human kidney. Breyer MD, Davis L, Jacobson HR, Breyer RM (1996) Am J Physiol 270(5 Pt 2): F912-8
    › Primary publication · 8928854 (PubMed)
  23. In situ hybridization and localization of mRNA for the rabbit prostaglandin EP3 receptor. Breyer MD, Jacobson HR, Davis LS, Breyer RM (1993) Kidney Int 44(6): 1372-8
    › Primary publication · 8301938 (PubMed)
  24. Alternative splicing generates multiple isoforms of a rabbit prostaglandin E2 receptor. Breyer RM, Emeson RB, Tarng JL, Breyer MD, Davis LS, Abromson RM, Ferrenbach SM (1994) J Biol Chem 269(8): 6163-9
    › Primary publication · 8119961 (PubMed)
  25. Mutational analysis of the fine specificity of binding of monoclonal antibody 51F to lambda repressor. Breyer RM, Sauer RT (1989) J Biol Chem 264(22): 13355-60
    › Primary publication · 2526816 (PubMed)
  26. Mutational analysis of ligand binding activity of beta 2 adrenergic receptor expressed in Escherichia coli. Breyer RM, Strosberg AD, Guillet JG (1990) EMBO J 9(9): 2679-84
    › Primary publication · 2167830 (PubMed) · PMC551972 (PubMed Central)