Emer M. Smyth, Ph.D.

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Adjunct Associate Professor of Pharmacology
Department: Systems Pharmacology and Translational Therapeutics

Contact information
Columbia University Irving Medical Center
Herbert Irving Comprehensive Cancer Center
Irving Cancer Research Center
1130 St. Nicholas Ave, Ste. 201
New York, NY 10032
New York, NY 10027
Office: 212-851-4878
Education:
B.Sc. (First Class Honor in Pharmacology)
National University of Ireland, University College, Dublin , 1990.
Ph.D. (Pharmacology)
National University of Ireland, University College, Dublin, Ireland, 1994.
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Description of Research Expertise

Research Summary:

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 the novel pathways directing the function and regulation of prostanoid receptors. Over the past decade the paradigm of GPCR homo- and hetero- dimerization has become and accepted phenomenon. We have show dimerization of IP and TP to form homo- and hetero- dimers with consequent changes in TP signaling and regulation. More recently we have identified formation of DP1 and DP2 homo- and hetero- dimers (but not IP-DP heterodimers) at comparable affinities. Currently we are investigating the molecular and cellular events that regulate prostanoid receptor dimerization in normal settings and cardiovascular disease.

A second major resarch focus of our laboratory emerged from the recent interest in the inducible COX-2 isoform and it partner in PGE2 generation, mPGES-1, as a chemopreventative or chemotherapeutic target in human cancer. Epidemiological reports demonstrate a reduction in the risk of mammary cancer with co-incident used of COX inhibitors. Our research examines the role of COX-1 and COX-2, in mammary cancer, and cancer related thrombosis, using mice engineered to lack specifically COX-2 or mPGES-1 expression the mammary epitheilium or in macrophages. Inititation, progression and metastasis of mammary tumors, and the incidence of cancer-related thrombosis, is currently under examination.

Selected Publications

Garg, R., Blando, J. M., Perez, C. J., Lal, P., Feldman, M. D., Smyth, E. M., Ricciotti, E., Grosser, T., Benavides, F., Kazanietz, M. G.: COX-2 mediates pro-tumorigenic effects of PKCepsilon in prostate cancer. Oncogene 2018.

Siangjong, L., Goldman, D. H., Kriska, T., Gauthier, K. M., Smyth, E. M., Puli, N., Kumar, G., Falck, J. R., Campbell, W. B.: Vascular hepoxilin and trioxilins mediate vasorelaxation through TP receptor inhibition in mouse arteries. Acta Physiol (Oxf) 219(1): 188-201, 2017.

Chen, E. P., Markosyan, N., Connolly, E., Lawson, J. A., Li, X., Grant, G. R., Grosser, T., FitzGerald, G. A., Smyth, E. M.: Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function. Carcinogenesis 35(8): 1788-97, 2014.

Khan A, Li D, Ibrahim S, Smyth E and Woulfe DS. : The physical association of the P2Y12 receptor with PAR4 regulates arrestin-mediated Akt activation. Mol Pharmacol. 86: 1-11, 2014.

Frey, AJ Ibrahim, S, Gleim, S, Hwa, J and Smyth, EM: Biased Suppression of Thromboxane A2 Receptor Homodimerization and Signaling Through Disruption of a Transmembrane GxxxGxxxL Helical Interaction Motif. J Lipid Rresearch 54(6): 1678-1690, Jun 2013.

Markosyan N, Chen EP, Evans RA, Ndong N, Vonderheide RH and Smyth EM.: Mammary carcinoma cell derived cyclooxygenase 2 suppresses tumor immune surveillance by enhancing intratumoral immune checkpoint activity. Breast Cancer Research 15(5): R75, 2013.

Siangjong, L., Gauthier, K. M., Pfister, S. L., Smyth, E. M., Campbell, W. B.: Endothelial 12(S)-HETE vasorelaxation is mediated by thromboxane receptor inhibition in mouse mesenteric arteries. Am J Physiol Heart Circ Physiol 304(3): H382-92, 2013.

Ibrahim, S., McCartney, A., Markosyan, N., Smyth, E. M.: Heterodimerization with the prostacyclin receptor triggers thromboxane receptor relocation to lipid rafts. Arterioscler Thromb Vasc Biol 33(1): 60-6, 2013.

Frey, A. J., Ibrahim, S., Gleim, S., Hwa, J., Smyth, E. M.: Biased suppression of TP homodimerization and signaling through disruption of a TM GxxxGxxxL helical interaction motif. J Lipid Res 54(6): 1678-90, 2013.

Chen, E. P., Smyth, E. M.: COX-2 and PGE2-dependent immunomodulation in breast cancer. Prostaglandins Other Lipid Mediat 96(1-4): 14-20, 2011.

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Last updated: 10/04/2018
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