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 Southwestern

Postdoctoral Fellow, Dept of Immunology, The Scripps Research Institute

Research Summary

Our work led to the deorphanization of GPR30, a Gs- coupled heptahelical transmembrane receptor now recognized by its current IUPHAR functional designate as G-protein-coupled estrogen receptor, GPER. Work in our lab revealed its molecular mechanism of action, including its specific estrogen binding characteristics, its coordinate regulation of fibrillogenesis and paracrine release of membrane-tethered EGF ligands as well as its unusual mechanism of desensitization via a ubiquitin/trans-Golgi network/proteasomal pathway. In addition, we have shown that GPER expression in primary breast tumors directly correlates with prognostic indices, such as tumor size and metastasis. Our current work is focused on further understanding its molecular mechanism of action and its biological role in the progression of female reproductive cancers.

Publications

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. 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. 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., 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. (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., 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.

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.

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.

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.

Filardo, E. J., Cheresh, D. A. (1994). A beta turn in the cytoplasmic tail of the integrin alpha v subunit influences conformation and ligand binding of alpha v beta 3. The Journal of biological chemistry, 269(6), 4641-7. 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., 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.

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., 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.