Emer Smyth, Ph.D.
Research Assistant Professor of
Pharmacology
Department of Pharmacology
808 Biomedical Research Building II/III
University of Pennsylvania School of Medicine
421 Curie Boulevard
Philadelphia, PA 19104-6061
Telephone: 215-573-2323
Fax: 215-573-9004
Email: emer@spirit.gcrc.upenn.edu
Link: http://www.itmat.upenn.edu
Department of Pharmacology
Emer Smyth, Ph.D.
Education:| 1990 | B.S. (Pharmacology) | University College, Dublin, Ireland |
| 1994 | Ph.D. (Pharmacology) | University College, Dublin, Ireland |
| 1994-1999 | Postdoctoral Fellow (Pharmacology) | University of Penn, Philadelphia, PA |
Prostanoids, a family of lipid mediators with multiple and diverse biological actions, are formed by the action of cyclooxygenase (COX) on arachidonic acid. A single gene product, encoding a G protein coupled receptor (GPCR) has been identified for prostacyclin (the IP), PGF2α (the FP) and TxA2 (the TP), while four distinct GPCRs for PGE2 (the EP1-4), and two for PGD2 (DP1 and DP2), have been cloned.
Our laboratory is interested in two opposing vasoactive prostanoids, prostacyclin (PGI2) and thromboxane (TxA2). PGI2, primarily derived from endothelial COX-2, protects against, while TxA2, a major product of platelet COX-1 contributes to, vascular disease. Both are elevated in vascular disorders, along with the free radical-derived isoprostanes. The actions of PGI2 and TxA2 are mediated through their receptors, IP and TP, while isoprostanes, may act as incidental TP ligands. IP and TP are frequently co-expressed and their ligands are increased in syndromes of vascular disease. We are investigating how these receptor systems modulate each otherÅfs function through heterodimerization and interaction with novel proteins, and the impact of such interactions on vascular function in normal and disease states.
Praticò D, Smyth EM, Violi F & FitzGerald GA: Local amplification of platelet function by 8-epi prostaglandin F2 α is not mediated by thromboxane receptor isoforms. J Biol Chem 271: 14916-14924, 1996.
Smyth EM, Nestor PV & FitzGerald GA: Agonist-induced phosphorylation of an epitope-tagged prostacyclin receptor. J Biol Chem 271: 33698-33704, 1996.
Smyth EM, Hong Li W & FitzGerald GA: Phosphorylation of the prostacyclin receptor during homologous desensitization: a critical role for PKC. J Biol Chem 273: 23258-23266, 1998.
Smyth EM, Austin SC & FitzGerald GA. Internalization and sequestration of the human prostacyclin receptor. J Biol Chem 275: 32037-32045, 2000.
Zhang Z-B, Austin, SC & Smyth EM. Role of glycosylation in membrane localization and function of the human prostacyclin receptor. Mol Pharmacol 60: 480-487, 2001.
Kothapalli, D, Stewart, SA, Smyth, EM, Azonobi, I, Puré, E & Assoian RK: IP activation inhibits proliferation of aortic smooth muscle cells by regulating CREB- and pocket protein-dependent cyclin A gene expression. Mol Pharmacol 64: 249-258, 2003.
Wilson SJ, Roche AM, Kostetskaia E, Smyth EM: Dimerization of the human receptors for prostacyclin and thromboxane facilitates thromboxane receptor-mediated cAMP generation. J Biol Chem 279: 53036-53047, 2004.
Egan KM Lawson JA, Fries S, Rader DJ, Smyth EM, FitzGerald, GA Prostacyclin confers Atheroprotection on Female Mice. Science, 306: 1954-57, 2004.
Wilson SJ, Roche AM, Kostetskaia E, Smyth EM. Dimerization of the Human Receptors for Prostacyclin and Thromboxane Facilitates Thromboxane Receptor-Mediated cAMP Generation. (2004) J Biol Chem. 279: 53036-47.
Wilson SJ, and Smyth EM. (2006). Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylation-dependent interaction with the δ subunit of cGMP phosphodiesterase 6. J Biol Chem., 281: 11780-11786.
Wilson SJ, Dowling JK Zhao, L Carnish E, Smyth EM. (2007) Regulation of thromboxane receptor trafficking through the prostacyclin receptor in vascular smooth muscle cells: role of receptor heterodimerization. Arterio. Throm. Vasc. Biol., 27: 290-296.
Wilson, SJ, McGinley, K, Huang, AY, and Smyth, EM. (2007) Heterodimerization of the α and β isoforms of the human thromboxane receptor enhances isoprostane signalling. Biochem. Biophys. Res. Comm., 352: 397-403
Awards, Honors, Membership in Honorary Societies:| • | National Research Service Award for Individual Postdoctoral Fellows #F32 HL09485 National Heart Lung and Blood Institute (1996-1998) |
| • | Travel Fellowship, 17th International Congress of Biochemistry and Molecular Biology and Annual Meeting of the American Society for Biochemistry and Molecular Biology (August 1997) |
| • | Travel Fellowship, Annual Meeting of the American Society for Biochemistry and Molecular Biology (May 1999) |
| • | Beginning Grant-in-Aid #9906209U, American Heart Association, Pennsylvania-Delaware Affiliate (1999-2001) |
| • | Fellow of the Arteriosclerosis, Thrombosis and Vascular Biology Council, American Heart Association (1999-present) |
| • | RO1HL066233-05, National Heart Lung and Blood Institute (2007-2012) |
| • | Mar 2004-Feb 2005 University Research Foundation Award, University of Pennsylvania |
| • | Mar 2005-Nov 2005 Abramson Cancer Center Pilot Project Award, University of Pennsylvania |
| • | May 2006: Member, American Society for Biochemistry and Molecular Biology |
| • | Jan 2007: Chemical Biology in Translation Pilot Award, Transdisciplinary Program in Translational Medicine and Therapeutics, University of Pennsylvania |
Laboratory Personnel:
| Jochen Graff, M.D. Postdoctoral Fellow jograff@mail.med.upenn.edu |
Mazell Tetruashvily Work Study Student |
Lab Address:
Institute for Translational Medicine and Therapeutics
829 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6160
Lab Telephone: 215-573-898-0255/0256
Lab Fax: 215-573-9004
Link: http://www.itmat.upenn.edu