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Edward J. Filardo, PhD

Portrait
Research Professor of Surgery - Surgical Oncology and Endocrine Surgery

Contact Information

Lab
4235 Medical Education Research Facilities
500 Newton Road
Iowa City, IA 52242
319-335-8982

Education

BS, Microbiology, University of California, Los Angeles
PhD, Microbiology, University of Texas Health Science Center
Postdoctoral Fellow, Dept of Microbiology, University of Texas Southwestern Medical School
Postdoctoral Research Fellow, Dept of Immunology, The Scripps Research Institute

Center, Program and Institute Affiliations

Holden Comprehensive Cancer Center

Research Summary

Work in my lab led to the identification and characterization of G-protein coupled estrogen receptor which has importance in metabolic regulation and advanced cancer. Current efforts are focused on: i) understanding its molecular mechanism of action and its biological role in the progression of female reproductive cancers, ii) developing cancer therapeutics that target this receptor and iii) evaluating the toxicological potency of environmental estrogens that act through GPER and their relevance for metabolic disorder and cancer.

Publications

Rouhimoghadam, M., Dong, J., Thomas, P. & Filardo, E. J. (2020). SAT-LB137 Rescue of Misfolded G-Protein Coupled Estrogen Receptor, GPER, from the Endoplasmic Reticulum via Natural and Synthetic Estrogens. Journal of the Endocrine Society, 4(Supplement_1). DOI: 10.1210/jendso/bvaa046.1976.

Phadke, S., Mott, S., Bashir, A., Bellizzi, A., Resnick, M., Sturtevant, A. & Filardo, E. (2020). Distribution of G-protein coupled estrogen receptor in treatment-naive triple negative breast cancer and association with clinicopathologic characteristics. (Vols. 80). (4) CANCER RESEARCH. DOI: 10.1158/1538-7445.SABCS19-P2-11-16.

Filardo, E. J. (2018). A role for G-protein coupled estrogen receptor (GPER) in estrogen-induced carcinogenesis: Dysregulated glandular homeostasis, survival and metastasis. The Journal of steroid biochemistry and molecular biology, 176, 38-48. PMID: 28595943.

Barton, M., Filardo, E. J., Lolait, S. J., Thomas, P., Maggiolini, M. & Prossnitz, E. R. (2018). Twenty years of the G protein-coupled estrogen receptor GPER: Historical and personal perspectives. The Journal of steroid biochemistry and molecular biology, 176, 4-15. PMID: 28347854.

Deming-Halverson, S. L., Graeber, C., Machan, J., Sabo, E., Zheng, W. & Filardo, E. J. (2016). Association of G-protein estrogen receptor (GPER) in primary breast cancer in Caucasian and Black women by tumor immunophenotype and menopausal status. (Vols. 76). CANCER RESEARCH. DOI: 10.1158/1538-7445.AM2016-2272.

Gaudet, H. M., Cheng, S. B., Christensen, E. M. & Filardo, E. J. (2015). The G-protein coupled estrogen receptor, GPER: The inside and inside-out story. Molecular and cellular endocrinology, 418 Pt 3, 207-19. PMID: 26190834.

Waters, E. M., Thompson, L. I., Patel, P., Gonzales, A. D., Ye, H. Z., Filardo, E. J., Clegg, D. J., Gorecka, J., Akama, K. T., McEwen, B. S. & Milner, T. A. (2015). G-protein-coupled estrogen receptor 1 is anatomically positioned to modulate synaptic plasticity in the mouse hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience, 35(6), 2384-97. PMID: 25673833.

Magruder, H. T., Quinn, J. A., Schwartzbauer, J. E., Reichner, J., Huang, A. & Filardo, E. J. (2014). The G protein-coupled estrogen receptor-1, GPER-1, promotes fibrillogenesis via a Shc-dependent pathway resulting in anchorage-independent growth. Hormones & cancer, 5(6), 390-404. PMID: 25096985.

Almey, A., Cannell, E., Bertram, K., Filardo, E., Milner, T. A. & Brake, W. G. (2014). Medial prefrontal cortical estradiol rapidly alters memory system bias in female rats: ultrastructural analysis reveals membrane-associated estrogen receptors as potential mediators. Endocrinology, 155(11), 4422-32. PMID: 25211590.

Naugle, M. M., Nguyen, L. T., Merceron, T. K., Filardo, E., Janssen, W. G., Morrison, J. H., Rapp, P. R. & Gore, A. C. (2014). G-protein coupled estrogen receptor, estrogen receptor a, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment. Journal of experimental zoology. Part A, Ecological genetics and physiology, 321(7), 399-414. PMID: 24862737.

Cheng, S. B., Dong, J., Pang, Y., LaRocca, J., Hixon, M., Thomas, P. & Filardo, E. J. (2014). Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone. Molecular and cellular endocrinology, 382(2), 950-9. PMID: 24239983.

Almey, A., Filardo, E. J., Milner, T. A. & Brake, W. G. (2012). Estrogen receptors are found in glia and at extranuclear neuronal sites in the dorsal striatum of female rats: evidence for cholinergic but not dopaminergic colocalization. Endocrinology, 153(11), 5373-83. PMID: 22919059.

Filardo, E. J. (2012). Gper and ER: Estrogen receptors with distinct biological roles in breast cancer. Inflammation and Allergy - Drug Targets, 11(4), 243-254.

Filardo, E. J., Thomas, P. (2012). Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology. Endocrinology, 153(7), 2953-62. PMID: 22495674.

Cheng, S. B., Filardo, E. J. (2012). Trans-Golgi Network (TGN) as a regulatory node for ß1-adrenergic receptor (ß1AR) down-modulation and recycling. The Journal of biological chemistry, 287(17), 14178-91. PMID: 22378779.

Magruder, H. T., Filardo, E. J. (2012). Epidermal growth factor receptor transactivation and fibronectin matrix assembly by the G-protein coupled receptor, GPER, requires a transmembrane signaling complex consisting of PTPN12, integrin alpha 5 beta 1, and MMP-3. (Vols. 26). FASEB JOURNAL.

Cheng, S. B., Graeber, C. T., Quinn, J. A. & Filardo, E. J. (2011). Retrograde transport of the transmembrane estrogen receptor, G-protein-coupled-receptor-30 (GPR30/GPER) from the plasma membrane towards the nucleus. Steroids, 76(9), 892-6. PMID: 21354433.

Cheng, S. B., Quinn, J. A., Graeber, C. T. & Filardo, E. J. (2011). Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway. The Journal of biological chemistry, 286(25), 22441-55. PMID: 21540189.

Yu, X., Filardo, E. J. & Shaikh, Z. A. (2010). The membrane estrogen receptor GPR30 mediates cadmium-induced proliferation of breast cancer cells. Toxicology and applied pharmacology, 245(1), 83-90. PMID: 20153348.

Quinn, J. A., Graeber, C. T., Frackelton, Jr, A. R., Kim, M., Schwarzbauer, J. E. & Filardo, E. J. (2009). Coordinate regulation of estrogen-mediated fibronectin matrix assembly and epidermal growth factor receptor transactivation by the G protein-coupled receptor, GPR30. Molecular endocrinology (Baltimore, MD), 23(7), 1052-64. PMID: 19342448.

Noel, S. D., Keen, K. L., Baumann, D. I., Filardo, E. J. & Terasawa, E. (2009). Involvement of G protein-coupled receptor 30 (GPR30) in rapid action of estrogen in primate LHRH neurons. Molecular endocrinology (Baltimore, MD), 23(3), 349-59. PMID: 19131510.

Xu, H., Qin, S., Carrasco, G. A., Dai, Y., Filardo, E. J., Prossnitz, E. R., Battaglia, G., Doncarlos, L. L. & Muma, N. A. (2009). Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus. Neuroscience, 158(4), 1599-607. PMID: 19095043.

Filardo, E. J., Quinn, J. A. & Sabo, E. (2008). Association of the membrane estrogen receptor, GPR30, with breast tumor metastasis and transactivation of the epidermal growth factor receptor. Steroids, 73(9-10), 870-3. PMID: 18289622.

Filardo, E., Quinn, J., Pang, Y., Graeber, C., Shaw, S., Dong, J. & Thomas, P. (2007). Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. Endocrinology, 148(7), 3236-45. PMID: 17379646.

Filardo, E. J., Graeber, C. T., Quinn, J. A., Resnick, M. B., Giri, D., DeLellis, R. A., Steinhoff, M. M. & Sabo, E. (2006). Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clinical cancer research : an official journal of the American Association for Cancer Research, 12(21), 6359-66. PMID: 17085646.

Sanchez-Esteban, J., Wang, Y., Filardo, E. J., Rubin, L. P. & Ingber, D. E. (2006). Integrins beta1, alpha6, and alpha3 contribute to mechanical strain-induced differentiation of fetal lung type II epithelial cells via distinct mechanisms. American journal of physiology. Lung cellular and molecular physiology, 290(2), L343-50. PMID: 16169900.

Filardo, E., Sabo, E., Graeber, C., Quinn, J., Giri, D., Delellis, R., Steinhoff, M. & Resnick, M. (2006). Association of GPR30, a seven membrane-spanning estrogen receptor with advanced (metastatic) breast carcinoma and its correlation with other classical prognostic factors. (Vols. 19). pp. 12-12. MODERN PATHOLOGY.

Filardo, E. J., Thomas, P. (2005). GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release. Trends in endocrinology and metabolism: TEM, 16(8), 362-7. PMID: 16125968.

Thomas, P., Pang, Y., Filardo, E. J. & Dong, J. (2005). Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology, 146(2), 624-32. PMID: 15539556.

Filardo, E. J., Quinn, J. A. & Graeber, C. T. (2003). Evidence Supporting a Role for Gpr30, an Orphan Member of the G-Protein-Coupled Receptor Superfamily, in Rapid Estrogen Signaling. In The Identities of Membrane Steroid Receptors. pp. 139-146. Springer US. DOI: 10.1007/978-1-4615-0339-2_17.

Filardo, E. J. (2002). Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. The Journal of steroid biochemistry and molecular biology, 80(2), 231-8. PMID: 11897506.

Filardo, E. J., Quinn, J. A., Frackelton, Jr, A. R. & Bland, K. I. (2002). Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Molecular endocrinology (Baltimore, MD), 16(1), 70-84. PMID: 11773440.

Filardo, E. J., Quinn, J. A., Bland, K. I. & Frackelton, Jr, A. R. (2000). Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Molecular endocrinology (Baltimore, MD), 14(10), 1649-60. PMID: 11043579.

Harler, M. B., Wakshull, E., Filardo, E. J., Albina, J. E. & Reichner, J. S. (1999). Promotion of neutrophil chemotaxis through differential regulation of beta 1 and beta 2 integrins. Journal of immunology (Baltimore, MD : 1950), 162(11), 6792-9. PMID: 10352300.

Pluschke, G., Vanek, M., Evans, A., Dittmar, T., Schmid, P., Itin, P., Filardo, E. J. & Reisfeld, R. A. (1996). Molecular cloning of a human melanoma-associated chondroitin sulfate proteoglycan. Proceedings of the National Academy of Sciences of the United States of America, 93(18), 9710-5. PMID: 8790396.

Chellaiah, M., Fitzgerald, C., Filardo, E. J., Cheresh, D. A. & Hruska, K. A. (1996). Osteopontin activation of c-src in human melanoma cells requires the cytoplasmic domain of the integrin alpha v-subunit. Endocrinology, 137(6), 2432-40. PMID: 8641196.

Filardo, E. J., Deming, S. L. & Cheresh, D. A. (1996). Regulation of cell migration by the integrin beta subunit ectodomain. Journal of cell science, 109 ( Pt 6), 1615-22. PMID: 8799848.

Yebra, M., Filardo, E. J., Bayna, E. M., Kawahara, E., Becker, J. C. & Cheresh, D. A. (1995). Induction of carcinoma cell migration on vitronectin by NF-kappa B-dependent gene expression. Molecular biology of the cell, 6(7), 841-50. PMID: 7579698.

Filardo, E. J., Brooks, P. C., Deming, S. L., Damsky, C. & Cheresh, D. A. (1995). Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo. The Journal of cell biology, 130(2), 441-50. PMID: 7542248.

Wickham, T. J., Filardo, E. J., Cheresh, D. A. & Nemerow, G. R. (1994). Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization. The Journal of cell biology, 127(1), 257-64. PMID: 7523420.

Filardo, E. J., Lee, M. F. & Humphries, E. H. (1994). Structural genes, not the LTRs, are the primary determinants of reticuloendotheliosis virus A-induced runting and bursal atrophy. Virology, 202(1), 116-28. PMID: 8009826.

Filardo, E. J., Cheresh, D. A. (1994). A ß turn in the cytoplasmic tail of the integrin av subunit influences conformation and ligand binding of avß3. Journal of Biological Chemistry, 269(6), 4641-4647. PMID: 7508446.

Filardo, E. J., Cheresh, D. A. (1994). A structural basis for bidirectional integrin signalling. Princess Takamatsu symposia, 24, 106-17. PMID: 8983068.

Filardo, E. J., Humphries, E. H. (1991). An avian retrovirus expressing chicken pp59c-myc possesses weak transforming activity distinct from v-myc that may be modulated by adjacent normal cell neighbors. Journal of virology, 65(12), 6621-9. PMID: 1942247.

Humphries, E. H., Filardo, E. J. (1990). The transforming activity of PP59C-MYC is weaker than that of v-myc. Current topics in microbiology and immunology, 166, 259-65. PMID: 2073806.