Vanderbilt-Ingram Cancer Center

The VICC.ORG Investigator Directory

Richard M. Breyer, Ph.D.

Professor
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
B-3301 Medical Center North
Nashville, TN 37232-2372
615-343-0257

Research Specialty:

Structure, Function and Biology of Prostanoid Receptors

Research Description:

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:

• Downey, JD, Sanders, CR, Breyer, RM Evidence for the presence of a critical disulfide bond in the mouse EP3γ receptor. Prostaglandins Other Lipid Mediat, 94(1-2), 53-8, 2011.
• Swan, CE, Breyer, RM Prostaglandin E2 modulation of blood pressure homeostasis: studies in rodent models. Prostaglandins Other Lipid Mediat, 96(1-4), 10-3, 2011.
• Jewell, ML, Breyer, RM, Currie, KP Regulation of calcium channels and exocytosis in mouse adrenal chromaffin cells by prostaglandin EP3 receptors. Mol Pharmacol, 79(6), 987-96, 2011.
• Howell, SC, Mittal, R, Huang, L, Travis, B, Breyer, RM, Sanders, CR CHOBIMALT: a cholesterol-based detergent. Biochemistry, 49(44), 9572-83, 2010.
• Smith, JP, Haddad, EV, Downey, JD, Breyer, RM, Boutaud, O PGE2 decreases reactivity of human platelets by activating EP2 and EP4. Thromb Res, 126(1), e23-9, 2010.
• Chen, J, Zhao, M, He, W, Milne, GL, Howard, JR, Morrow, J, Hebert, RL, Breyer, RM, Chen, J, Hao, CM Increased Dietary NaCl induces Renal Medullary PGE2 Production and Natriuresis via the EP2 Receptor. Am J Physiol Renal Physiol, 2008.
• Babaev, VR, Chew, JD, Ding, L, Davis, S, Breyer, MD, Breyer, RM, Oates, JA, Fazio, S, Linton, MF Macrophage EP4 deficiency increases apoptosis and suppresses early atherosclerosis. Cell Metab, 8(6), 492-501, 2008.
• Macias-Perez, IM, Zent, R, Carmosino, M, Breyer, MD, Breyer, RM, Pozzi, A Mouse EP3 alpha, beta, and gamma receptor variants reduce tumor cell proliferation and tumorigenesis in vivo. J Biol Chem, 283(18), 12538-45, 2008.
• 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 Antihypertensive effects of selective prostaglandin E2 receptor subtype 1 targeting. J Clin Invest, 117(9), 2496-505, 2007.
• Zhou, W, Blackwell, TS, Goleniewska, K, O''neal, JF, Fitzgerald, GA, Lucitt, M, Breyer, RM, Peebles, RS Prostaglandin I2 analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells. J Leukoc Biol, 81(3), 809-17, 2007.
• Kamiyama, M, Pozzi, A, Yang, L, DeBusk, LM, Breyer, RM, Lin, PC EP2, a receptor for PGE2, regulates tumor angiogenesis through direct effects on endothelial cell motility and survival. Oncogene, 25(53), 7019-28, 2006.
• Hata, AN, Lybrand, TP, Breyer, RM Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. J Biol Chem, 280(37), 32442-51, 2005.
• Tian, C, Breyer, RM, Kim, HJ, Karra, MD, Friedman, DB, Karpay, A, Sanders, CR Solution NMR spectroscopy of the human vasopressin V2 receptor, a G protein-coupled receptor. J Am Chem Soc, 127(22), 8010-1, 2005.
• Hata, AN, Lybrand, TP, Marnett, LJ, Breyer, RM Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol Pharmacol, 67(3), 640-7, 2005.
• Pozzi, A, Yan, X, Macias-Perez, I, Wei, S, Hata, AN, Breyer, RM, Morrow, JD, Capdevila, JH Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J Biol Chem, 279(28), 29797-804, 2004.
• Schneider, A, Guan, Y, Zhang, Y, Magnuson, MA, Pettepher, C, Loftin, CD, Langenbach, R, Breyer, RM, Breyer, MD Generation of a conditional allele of the mouse prostaglandin EP4 receptor. Genesis, 40(1), 7-14, 2004.
• Schneider, A, Zhang, Y, Zhang, M, Lu, WJ, Rao, R, Fan, X, Redha, R, Davis, L, Breyer, RM, Harris, R, Guan, Y, Breyer, MD Membrane-associated PGE synthase-1 (mPGES-1) is coexpressed with both COX-1 and COX-2 in the kidney. Kidney Int, 65(4), 1205-13, 2004.
• Hata, AN, Breyer, RM Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther, 103(2), 147-66, 2004.
• Yang, Li, Yamagata, Noboru, Yadav, Rajwardhan, Brandon, Suzanne, Courtney, Regina L, Morrow, Jason D, Shyr, Yu, Boothby, Mark, Joyce, Sebastian, Carbone, David P, Breyer, Richard M, Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor.. J Clin Invest, 111727-35, 2003.
• Ochsner, Scott A, Russell, Darryl L, Day, Anthony J, Breyer, Richard M, Richards, Joanne S, Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice.. Endocrinology, 1441008-19, 2003.
• Hata, Aaron N, Zent, Roy, Breyer, Matthew D, Breyer, Richard M, Expression and molecular pharmacology of the mouse CRTH2 receptor.. J Pharmacol Exp Ther, 306463-70, 2003.
• Saito, Osamu, Guan, Youfei, Qi, Zhonghua, Davis, Linda S, Kömhoff, Martin, Sugimoto, Yukihiko, Narumiya, Shuh, Breyer, Richard M, Breyer, Matthew D, Expression of the prostaglandin F receptor (FP) gene along the mouse genitourinary tract.. Am J Physiol Renal Physiol, 284F1164-70, 2003.
• Zhang, Y, Schneider, A, Rao, R, Lu, WJ, Fan, X, Davis, L, Breyer, RM, Breyer, MD, Guan, Y Genomic structure and genitourinary expression of mouse cytosolic prostaglandin E(2) synthase gene. Biochim Biophys Acta, 1634(1-2), 15-23, 2003.
• Breyer, MD, Hébert, RL, Breyer, RM Prostanoid receptors and the urogenital tract. Curr Opin Investig Drugs, 4(11), 1343-53, 2003.
• Guan, Y., Stillman, B.A., Zhang, Y., Schneider, A., Saito, O., Davis, L.S., Redha, R., Breyer, R.M., and Breyer, M.D "Cloning and expression of the rabbit prostaglandin EP2 receptor." BMC Pharmacol., 214, 2002.
• Guan, Y, Stillman, BA, Zhang, Y, Schneider, A, Saito, O, Davis, LS, Redha, R, Breyer, RM, Breyer, MD Cloning and expression of the rabbit prostaglandin EP2 receptor. BMC Pharmacol, 214, 2002.
• Imig, J.D, Breyer, M.D., and Breyer, R.M "Contribution of Prostaglandin EP2 Receptors to Renal Microvascular Reactivity in Mice." Am. J. Physiol., 283F415-F422, 2002.
• Ochsner, S.A. Russell, D.L., Day, A.J., Breyer, R.M., and Richards, J.S "Decreased expression of TNF-a stimulated gene 6 mRNA and protein in cumulus cells of the cyclooxygenase-2 knockout mouse." Endocrinology, (In Press)2002.
• Li, X., Pilbeam C.C., Pan, L., Breyer, R.M. , and Raisz, L.G "Effects of prostaglandin E2 on gene expression in primary osteoblastic cells from prostaglandin receptor knockout mice." Bone, 30567-573, 2002.
• Montine, T.J., Milatovic, D., Morrow, J.D., and Breyer, R.M "Lipopolysaccharide- but not kainite-induced cerebral oxidative damage is EP2 receptor dependent." J. Neurochem., 83463-470, 2002.
• Montine, TJ, Milatovic, D, Gupta, RC, Valyi-Nagy, T, Morrow, JD, Breyer, RM Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent. J Neurochem, 83(2), 463-70, 2002.
• Qi, Z, Hao, CM, Langenbach, RI, Breyer, RM, Redha, R, Morrow, JD, Breyer, MD Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. J Clin Invest, 110(1), 61-9, 2002.
• Qi, Z., Hao, C.M., Langenbach, R.L., Breyer, R. M., Redha, R.D., Morrow, J.D., and Breyer, M.D "Opposite effects of cyclooxygenases-1 and -2 activity on the pressor response to angiotensin II." J.Clin.Invest., 11061-69, 2002.
• Li, X., Tomita, M., Pilbeam, C.C., Breyer, R.M., and Raisz, L.G "Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo." Prostaglandins Other Lipid Mediat., 67173-180, 2002.
• Cheng, H.F., Wang, S.-W., Zhang, M.-Z., McKanna, J.A., Breyer, R.M., and Harris, R.C "Prostaglandins that increase rennin production in response to ACE are not mediated by EP2 or COX-1." Am. J. Physiol., 283R638-R646, 2002.
• Breyer, Richard M, Kennedy, Christopher R J, Zhang, Yahua, Guan, Youfei, Breyer, Matthew D, Targeted gene disruption of the prostaglandin E2 EP2 receptor.. Adv Exp Med Biol, 507321-6, 2002.
• Matsumoto, H., Ma, W. Smalley, W., Trzaskos, J., Breyer, R.M., and Dey, S.K "Diversification of cyclooxygenase -2 derived prostaglandins in ovulation and implantation." Biol. Reprod., 641557-1565, 2001.
• Stecenko, A.A., King, G., Torii, K., Breyer, R.M., Dworski, R., Blackwell, T.S., Christman, J.W., and Brigham, K.L "Dysregulated cytokine production by cultured human cystic fibrosis bronchial epithelial cells." Inflammation, 25145-155, 2001.
• Stecenko, AA, King, G, Torii, K, Breyer, RM, Dworski, R, Blackwell, TS, Christman, JW, Brigham, KL Dysregulated cytokine production in human cystic fibrosis bronchial epithelial cells. Inflammation, 25(3), 145-55, 2001.
• Fortner, C.N., Breyer, R.M., and Paul, R.J "EP2 Receptors Mediate Airway Relaxation To Substance P, ATP, And Prostaglandin E2." Am. J. Physiol., 281L469-L474, 2001.
• Figueroa, D.J., Breyer, R.M., DeFoe, S.K., Kargman, S., Daugherty, B.L., Waldburger, K., Zhizen, Z., Jones, T.R., Austin, C.P., and Evans, J.P "Expression of the cysteinyl leukotriene 1 (CysLT1) receptor in normal human lung and peripheral blood leukocytes." Am. J. Resp. Crit Care Med., 163226-233, 2001.
• Figueroa, DJ, Breyer, RM, Defoe, SK, Kargman, S, Daugherty, BL, Waldburger, K, Liu, Q, Clements, M, Zeng, Z, O'Neill, GP, Jones, TR, Lynch, KR, Austin, CP, Evans, JF Expression of the cysteinyl leukotriene 1 receptor in normal human lung and peripheral blood leukocytes. Am J Respir Crit Care Med, 163(1), 226-33, 2001.
• Breyer, MD, Breyer, RM G protein-coupled prostanoid receptors and the kidney. Annu Rev Physiol, 63579-605, 2001.
• Guan, Y., Zhang, Y., Schneider, A., Davis, L., Breyer, R.M., and Breyer, M.D "Perixosome proliferator-activated receptor γ(PPARγ) activity is associated with renal microvasculature." Am. J. Physiol., 28F1036-F1046, 2001.
• Guan, Y, Zhang, Y, Schneider, A, Davis, L, Breyer, RM, Breyer, MD Peroxisome proliferator-activated receptor-gamma activity is associated with renal microvasculature. Am J Physiol Renal Physiol, 281(6), F1036-46, 2001.
• Breyer, RM Prostaglandin EP(1) receptor subtype selectivity takes shape. Mol Pharmacol, 59(6), 1357-9, 2001.
• Breyer, RM, Bagdassarian, CK, Myers, SA, Breyer, MD Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol, 41661-90, 2001.
• Guan, Y, Zhang, Y, Schneider, A, Riendeau, D, Mancini, JA, Davis, L, Kömhoff, M, Breyer, RM, Breyer, MD Urogenital distribution of a mouse membrane-associated prostaglandin E(2) synthase. Am J Physiol Renal Physiol, 281(6), F1173-7, 2001.
• Guan, Y., Zhang, Y., Schneider, A., Riendeau, D., Mancini, J.A., Davis, L., Kömhoff, M., Breyer, R.M., and Breyer, M.D "Urogenital distribution of a mouse membrane-associated prostaglandin E2 synthase." Am. J. Physiol., 281F1173-F1177, 2001.
• Zhang, Y., Guan Y., Schneider, A., Brandon, S., Breyer, R. M., and Breyer M. D "Characterization of murine vasopressor and vasodepressor prostaglandin E2 receptors." Hypertension, 351129-1134, 2000.
• Zhang, Y, Guan, Y, Schneider, A, Brandon, S, Breyer, RM, Breyer, MD Characterization of murine vasopressor and vasodepressor prostaglandin E(2) receptors. Hypertension, 35(5), 1129-34, 2000.
• Li, X., Okada, Y., Pilbeam C.C., Kennedy, C.R.J., Breyer, R.M. , and Raisz, L.G "Knockout of the Prostaglandin EP2 Receptor Impairs Osteoclastogenesis in vitro." Endocrinology, 1412054-2061, 2000.
• Breyer, MD, Breyer, RM Prostaglandin E receptors and the kidney. Am J Physiol Renal Physiol, 279(1), F12-23, 2000.
• Breyer, MD, Breyer, RM Prostaglandin receptors: their role in regulating renal function. Curr Opin Nephrol Hypertens, 9(1), 23-9, 2000.
• Breyer, RM, Kennedy, CR, Zhang, Y, Breyer, MD Structure-function analyses of eicosanoid receptors. Physiologic and therapeutic implications. Ann N Y Acad Sci, 905221-31, 2000.
• Sheller, J. R., Mitchell, D., Meyrick, B., Oates, J. A. and Breyer, R. M "The EP2 Receptor Mediates Bronchodilation in Mice." J. Applied Physiol, 882214-2218, 2000.
• Kennedy, C. R. J., Zhang, Y., Brandon, S, Guan, Y., Coffee K., Funk, C. D., Magnuson, M. A., Oates, J. A., Breyer, M. D., and Breyer, R. M "Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor." Nature Medicine, 5217-220, 1999.
• Audoly, L., Ma, L., Feoktistov, I. Breyer, M.D. and Breyer, R. M "EP3 receptor activation of cAMP response element mediated gene transcription." J. Pharmacol. Exper. , 289140-148, 1999.
• Guan, YF, Zhang, YH, Breyer, RM, Davis, L, Breyer, MD Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human transitional bladder cancer and its role in inducing cell death. Neoplasia, 1(4), 330-9, 1999.
• Stillman, BA, Breyer, MD, Breyer, RM Importance of the extracellular domain for prostaglandin EP(2) receptor function. Mol Pharmacol, 56(3), 545-51, 1999.
• Audoly, LP, Ma, L, Feoktistov, I, de Foe, SK, Breyer, MD, Breyer, RM Prostaglandin E-prostanoid-3 receptor activation of cyclic AMP response element-mediated gene transcription. J Pharmacol Exp Ther, 289(1), 140-8, 1999.
• Kennedy, CR, Zhang, Y, Brandon, S, Guan, Y, Coffee, K, Funk, CD, Magnuson, MA, Oates, JA, Breyer, MD, Breyer, RM Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. Nat Med, 5(2), 217-20, 1999.
• Stillman, BA, Audoly, L, Breyer, RM A conserved threonine in the second extracellular loop of the human EP2 and EP4 receptors is required for ligand binding. Eur J Pharmacol, 357(1), 73-82, 1998.
• Guan, Y, Zhang, Y, Breyer, RM, Fowler, B, Davis, L, Hébert, RL, Breyer, MD Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor. J Clin Invest, 102(1), 194-201, 1998.
• Breyer, MD, Zhang, Y, Guan, YF, Hao, CM, Hebert, RL, Breyer, RM Regulation of renal function by prostaglandin E receptors. Kidney Int Suppl, 67S88-94, 1998.
• Feoktistov, I, Breyer, RM, Biaggioni, I Prostanoid receptor with a novel pharmacological profile in human erythroleukemia cells. Biochem Pharmacol, 54(8), 917-26, 1997.
• Audoly, L, Breyer, RM Substitution of charged amino acid residues in transmembrane regions 6 and 7 affect ligand binding and signal transduction of the prostaglandin EP3 receptor. Mol Pharmacol, 51(1), 61-8, 1997.
• Audoly, L.P., and Breyer, R.M "The second extracellular loop of the prostaglandin EP3 receptor is an essential determinant of ligand selectivity." J. Biol. Chem., 27213475-13478, 1997.
• Audoly, L, Breyer, RM The second extracellular loop of the prostaglandin EP3 receptor is an essential determinant of ligand selectivity. J Biol Chem, 272(21), 13475-8, 1997.
• Breyer, M. D., Jacobson, H. R., Davis, L.S., and Breyer, R. M "Differential Localization of Prostaglandin E Receptor Subtypes in Human Kidney." Am. J. Physiol, 270F912-F918, 1996.
• Breyer, R. M., Emeson, R. B., Breyer, M. D., Davis, L.S., Abromson, R.M., and Ferrenbach, S. F "Alternative Splicing Generates Multiple Isoforms of a Rabbit Prostaglandin E2 Receptor." J. Biol. Chem., 61636169, 1994.
• Breyer, RM, Emeson, RB, Tarng, JL, Breyer, MD, Davis, LS, Abromson, RM, Ferrenbach, SM Alternative splicing generates multiple isoforms of a rabbit prostaglandin E2 receptor. J Biol Chem, 269(8), 6163-9, 1994.
• Breyer, MD, Jacobson, HR, Davis, LS, Breyer, RM In situ hybridization and localization of mRNA for the rabbit prostaglandin EP3 receptor. Kidney Int, 44(6), 1372-8, 1993.