INSTITUTE OF BIOLOGY, MEDICINAL CHEMISTRY & BIOTECHNOLOGY
 
  Drug Discovery
  Computational Chemistry
  Molecular Analysis
  Organic and Organometallic Chemistry
  Medicinal Chemistry
  Structural Biology & Chemistry
  Molecular Endocrinology
  Signal Mediated Gene Expression
  Molecular & Cellular Ageing
  Biomedical Applications
  Holistic Approaches in Health
  Chemical Carcinogenesis and Genetic Toxicology
  Metabolic Engineering-Bioinformatics
  Biotechnology
  Enzyme and Synthetic Biotechnology
  Biomimetics & Nanobiotechnology

 

Molecular Endocrinology

 

Research team

Michael N. Alexis, PhD, Research Professor
Dimitra J. Mitsiou, PhD, Research Assistant Professor
Vassiliki Ganou, MSc, Technical Research Scientist
Aggeliki K. Meligova, Post doctoral fellow
Vassilis Mersinias, Post doctoral fellow
Maria Poulou, Post doctoral fellow
Viky Kyriakou, PhD student
Sofia Zerva, PhD student
Dimitra Siakouli, Graduate student

 

The Molecular Endocrinology Team carries out research on the molecular physiology and pharmacology of steroid receptors with the scope of exploiting their potential in the prognosis and treatment of endocrine-related degenerative diseases. The R&D activities of the Team are developing in two closely inter-related research directions investigating the role of, 1) estrogen receptors as prognostic markers and therapeutic targets and, 2) glucocorticoid receptor as modulator of gene expression. In recent years, the R&D activities the Programme were supported by 14 competitively funded projects from National and EU sources. During this period, researchers of the Team were also involved in the training of 5 undergraduate, 3 postgraduate and 12 PhD students and 6 postdoctoral fellows and in transfer of know-how to the industry in the context of 6 joint projects.


Research objectives

1.         Understanding the molecular determinants of breast cancer resistance to antiestrogens:

(a) Over 60% of primary breast tumours express estrogen receptor α (ERα). The receptor is known to mediate the stimulatory effect of estrogen on tumour growth and the inhibitory effect of antiestrogens, drugs designed to block the effects of estrogen through ERα/ERβ. The antiestrogen Tamoxifen is widely acknowledged to increase progression-free survival and overall survival of patients with ERα-positive breast tumours. However, the vast majority of patients on Tamoxifen monotherapy eventually progresses. Resistance to the drug is mostly due to Tamoxifen-induced upregulation of ERα crosstalk with receptor tyrosine kinases (RTK) of the HER family, mainly EGFR/HER2, and/or with PI3K, key downstream transducer of RTK signalling. Patients that have progressed on Tamoxifen are usually treated with Lapatinib, a dual EGFR/HER2 inhibitor. However, breast tumours are known to escape Lapatinib blockade, while retaining sensitivity to PI3K inhibitors. New inhibitors generated by the POM consortium are tested using PI3KCA and/or PTEN mutant cells in culture and in mouse xenografts. A genome-wide microarray analysis of cells’ response to Tamoxifen alone and in combination with lead inhibitors is possible to reveal markers of sensitivity to new combinatorial therapies and, in addition, point to new targets that might be associated with resistance to such therapies. The above tasks are funded by Research Program COOPERATION: project 09ΣΥΝ-11-675 (2010-2014): “PIK3CA Oncogenic Mutations in Breast and Colon Cancers: Development of Targeted Anticancer Drugs and Diagnostics (POM)” Project participants: Genetics Division, BRFAA - Signal-mediated Gene Expression, Molecular Endocrinology and Metabolic Engineering & Bioinformatics Teams, IBCMB, NHRF - BRI, FORTH - ProActina SA - Pharmathen Pharmaceuticals - Bioiatriki SA.

(b) Breast cancer resistance to Tamoxifen could be also due to aberrant activation of NFKB, key transducer of pro-inflammatory signaling. Suppression of NFKB activity has been shown to restore sensitivity of ERα-positive breast cancer cells to tamoxifen. The glucocorticoid receptor (GR) is key transducer of anti-inflammatory signaling. However, clinical applications of GCs are limited by severe side-effects due to GRE (GR-binding DNA element)-dependent GR-mediated induction of the hyperglycemic and osteoporotic actions of GCs. Non-steroidal GR ligands reportedly can dissociate the GRE/inductive from the NFKB/suppressive effects of GCs. A task force of 8 IBMCB researchers is currently involved in the development of dissociated GR ligands. Potential leads will be tested using Tamoxifen-resistant NFKB-overexpressing breast cancer cells in culture and in mouse xenografts. A genome-wide microarray analysis of these cells’ responses to Tamoxifen alone and in combination with a selected lead is possible to reveal markers of sensitivity to the combinatorial therapy. The above tasks are funded by Research Program KRIPIS: Project STHENOS (2013-2015): Targeted therapeutic approaches against ageing and degenerative diseases, cancer in particular”. Participating IBMCB teams: Molecular Endocrinology, Metabolic Engineering & Bioinformatics, Organic & Organometallic Chemistry, Pharmaceutical Chemistry, Structural Biology & Chemistry, Molecular Analysis.
 
2.         Elucidation of the prognostic and therapeutic significance of estrogen receptor β in Triple Negative Breast Cancer: TNBC is a subtype of ERα-negative breast cancer that lacks HER2 overexpression as well as ERα and PR (progesterone receptor) expression, represents approx. 15% of all breast cancer cases and is the dominant phenotype in patients-carriers of BRCA1 gene mutations. TNBC is known to predominantly express two isoforms of ERβ, ERβ1 & ERβ2, of which only ERβ1 is known to bind estradiol with high affinity. High-affinity ligands for ERβ2 are presently unknown. We recently reported that ERβ2 is associated with poor prognosis in ERα-negative breast carcinoma. However, the prognostic and therapeutic significance of ERβ1 and ERβ2 in TNBC remain essentially unknown. We set out, i) to assess the clinical significance of ERβ1 and ERβ2 in TNBC by associating receptor expression levels with disease outcome in a cohort of 500 cases of TNBC and, ii) to unravel the molecular determinants of alleged ERβ1 and ERβ2 activity against wild-type and mutant BRCA1-bearing TNBC cell lines by determining their chromatin binding sites and transcriptional read-outs in the presence of estrogen and/or tamoxifen. The above tasks are funded by Research Programs THALES: Project 85355 (2012-15): “Molecular sub-typing of Triple Negative Breast Cancer (TNBC)”. Project Participants: Department of Medical Oncology, School of Medicine, Univ. of Thessaloniki - Molecular Diagnostics Laboratory, National Centre of Scientific Research ‘Demokritos’ - Department of Basic Medical Sciences, School of Medicine, Univ. of Athens - Molecular Endocrinology Team, IBMCB, NHRF.

3.         Development of Selective ER Modulators (SERMs) with osteoprotective, neuroprotective and/or anticancer activities: The increase in life expectancy has significantly increased morbidity and mortality due to post-menopausal endocrine-related degenerative diseases, including senile dementia, osteoporosis and breast cancer, in particular. Substituting for endogenous estrogen with exogenous hormones has been shown to increase the risk for breast cancer. SERMs such as raloxifene act as estrogens in the bone and as anti-estrogens in the breast and uterus and therefore constitute a safe alternative to estrogen. However, long term patients’ compliance with SERM treatment is poor. The aim of this task is to discover natural SERMs that display significant chemopreventive potential against postmenopausal osteoporosis and hypercholesterolemia, while lacking stimulatory activity in the breast and uterus. This task entails 1) in vitro evaluation and prioritization of hundreds of new compounds using cell lines; 2) determination of the transcriptomic and metabonomic profiles of the compounds that are most active in promoting osteoblastogenesis and/or inhibiting osteoclastogenesis in vitro; 3) evaluation of the potential of selected lead compounds to prevent hypercholesterolemia and osteoporosis in the ovariectomized mouse. The above tasks are funded by Research Programs THALES: Project 80038 (2012-15): “Development of new selective estrogen receptor modulators for preventing menopause consequences (SERMENCO)”. Project Participants: Department of Pharmacognosy & Natural Products Chemistry, School of Pharmacy, Univ. of Athens - Department of Chemistry, Agricultural Univ. of Athens - Molecular Endocrinology Team, IBMCB, NHRF; and COOPERATION: Project 09SYN-11-1076 (2011-2015): “Development of natural products and analogues for osteoporosis prevention: transcriptomic, proteomic & metabolomic approaches”. Project Participants: Department of Pharmacognosy & Natural Products Chemistry, School of Pharmacy, Univ. of Athens - Department of Surgery, School of Medicine, Univ. of Athens – Molecular Endocrinology Team, IBMCB, NHRF - Lavipharm SA.

Research Highlights

1.         We produced antibodies to GR, ERα, ERβ1, ERβ2 and ERβ (the sum of ERβ1-5) and validated their performance in many immunochemical methods, including immunohistochemistry (IHC) and chromatin immunoprecipitation (ChIP).1,2 The antibodies were proven to be key tools for probing the GR-NFKB interactome at genome-wide scale,3 the expression of ERβ1 and ERβ2 in disease4 and the clinical significance of ERβ1 and ERβ2 in (ERα)-positive5 and (ERα)-negative breast cancer.6 Two antibodies are presently marketed by DIAGENODE SA.7,8  

[1] Siriani D et al, J Steroid Biochem Mol Biol. 2003 Feb;84(2-3):171-80,  [2] Chantzi NI et al, Steroids 2011 Sep-Oct;76(10-11):974-85, [3]  Rao NRA et al, Genome Research 2011 Sep;21(9):1404-16, [4] Chantzi NI et al (submitted),  [5] Dhimolea E et al (in preparation), [6] Chantzi NI et al, Cancer Res Clin Oncol. 2013 Sep;139(9):1489-98, [7] ERα monoclonal antibody – Classic (Catalogue No C15100066 / AC-066-100), [8] GR monoclonal antibody - Classic (C15200010 / MAb-010-050)

Figure 1: Immunostaining of normal (A) and hyperplastic (B) human breast tissue using home made monoclonal antibody B1C1 to estrogen receptor beta (ERβ1) (x400). (Chantzi et al, Insights into ectopic estrogen receptor expression, nucleocytoplasmic distribution and interaction with chromatin obtained with new antibodies to estrogen receptor α and β. Steroids 2011;76:974-85).

2.         Using our antibodies we showed for the first time that high ERβ2 expression is an independent marker of early relapse in ERα-negative breast carcinoma.1 A study of 500 cases of TNBC is currently underway in the context of THALES Project 85355 (2012-15) in order to unravel the prognostic and potentially therapeutic significance of ERβ1 and ERβ2 and the molecular determinants of their action in TNBC.
[1] Chantzi NI et al, Cancer Res Clin Oncol. 2013 Sep;139(9):1489-98.

3.         We recently reported on the synthesis of a series of new stilbenoid derivatives and on their neuroprotective activity as assessed using glutamate-challenged HT22 hippocampal neurons, known to model oxidative stress-induced neuronal cell death.1 Several of the derivatives displayed neuroprotective activity at the low nM range. In addition, they lacked stimulatory activity on breast and endometrial cancer cells and ability to interfere with aryl hydrocarbon receptor-mediated gene expression. The derivatives are considered as lead neuroprotective agents of low endocrine cancer risk and of low risk of interference with drug activation and detoxification mechanisms
[1] Villalonga-Barber C et al, Bioorg Med Chem. 2011 Jan 1;19(1):339-51.

4.         Genome-wide footprint of glucocorticoid receptor (GR) and nuclear factor kappa-b (NFKB) crosstalk.


Figure 2: The global interaction of GR and NFKB on chromatin was assessed using ChIP-sequencing. Genome-wide profiles of GR and p65 (major NF-kB subunit) binding sites and target genes provided a footprint of GR-NFKB crosstalk and substantially contributed to understanding the networks underlying glucocorticoid and inflammatory signaling pathways. (Rao et al. 2011, Co-activation of GR and NFKB alters the repertoire of their binding sites and target genes. Genome Res. 2011; 21(9):1404-16.). 

Peer-reviewed Publications†, Patents & Competitively Funded Projects (2005 -  ): Includes publications of former ME researcher Professor CE Sekeris (1933 - 2009).

  1. Panagiotidou E, Zerva S, Mitsiou DJ, Alexis MN, Kitraki E. Perinatal exposure to low dose bisphenol A affects the neuroendocrine stress response in rats. J Endocrinol. 2013 Dec 9. [Epub ahead of print]
  2. Chantzi NI, Tiniakos DG, Palaiologou M, Goutas N, Filippidis T, Vassilaros SD, Dhimolea E, Mitsiou DJ, Alexis MN. Estrogen receptor beta 2 is associated with poor prognosis in estrogen receptor alpha-negative breast carcinoma. J Cancer Res Clin Oncol. 2013 Sep;139(9):1489-98.
  3. Polasek J, Queiroz EF, Marcourt L, Meligova AK, Halabalaki M, Skaltsounis AL, Alexis MN, Prajogo B, Wolfender JL, Hostettmann K. Peltogynoids and 2-Phenoxychromones from Peltophorum pterocarpum and Evaluation of Their Estrogenic Activity. Planta Med. 2013 Apr;79(6):480-6
  4. Roumeliotis TI, Halabalaki M, Alexi X, Ankrett D, Giannopoulou EG, Skaltsounis AL, Sayan BS, Alexis MN, Townsend PA, Garbis SD. Pharmaco-proteomic Study of the Natural Product Ebenfuran III in DU-145 Prostate Cancer Cells: The Quantitative and Temporal Interrogation of Chemically Induced Cell Death at the Protein Level. J Proteome Res. 2013 Mar 12. [Epub ahead of print].
  5. Fokialakis N, Alexi X, Aligiannis N, Siriani D, Meligova AK, Pratsinis H, Mitakou S, Alexis MN. Ester and carbamate ester derivatives of Biochanin A: synthesis and in vitro evaluation of estrogenic and antiproliferative activities. Bioorg Med Chem. 2012 May 1;20(9):2962-70.
  6. Simoes DC, Psarra AM, Mauad T, Pantou I, Roussos C, Sekeris CE, Gratziou C. Glucocorticoid and estrogen receptors are reduced in mitochondria of lung epithelial cells in asthma. PLoS One. 2012;7(6):e39183.
  7. Psarra AM, Sekeris CE. Glucocorticoids induce mitochondrial gene transcription in HepG2 cells Role of the mitochondrial glucocorticoid receptor. Biochim Biophys Acta. 2011 Oct;1813(10):1814-21.
  8. Chantzi NI, Meligova AK, Dhimolea E, Petrou CC, Mitsiou DJ, Pechtelidou A, Florentin I, Kitraki E, Cordopatis P, Tiniakos DG, Alexis MN. Insights into ectopic estrogen receptor expression, nucleocytoplasmic distribution and interaction with chromatin obtained with new antibodies to estrogen receptor α and β. Steroids 2011 Sep-Oct;76(10-11):974-85.
  9. Rao NRA, McCalman MT, Moulos P, Francoijs KJ, Chatziioannou A, Kolisis FN, Alexis MN, Mitsiou DJ, Stunnenberg HG. Co-activation of GR and NFKB alters the repertoire of their binding sites and target genes. Genome Res. 2011 Sep;21(9):1404-16.
  10. Koufaki M, Tsatsaroni A, Alexi X, Guerrand H, Zerva S, Alexis MN. Isoxazole substituted chromans against oxidative stress-induced neuronal damage. Bioorg Med Chem. 2011 Aug 15;19(16):4841-50.
    11. Koukoulitsa C, Durdagi S, Siapi E, Villalonga-Barber C, Alexi X, Steele BR, Micha-Screttas M, Alexis
  11. Tsantili-Kakoulidou A, Mavromoustakos T. Comparison of thermal effects of stilbenoid analogs in lipid bilayers using differential scanning calorimetry and molecular dynamics: correlation of thermal effects and topographical position with antioxidant activity. Eur Biophys J. 2011 Jul;40(7):865-75.
  12. Lagiou A, Samoli E, Georgila C, Zourna P, Barbouni A, Vassilarou D, Tsikkinis A, Sekeris CE, Trichopoulos D, Lagiou P. Diet and expression of estrogen alpha and progesterone receptors in malignant mammary tissue. Nutr Cancer. 2011 Jan;63(1):65-72.
  13. Villalonga-Barber C, Meligova AK, Alexi X, Steele BR, Kouzinos CE, Screttas CG, Katsanou ES, Micha-Screttas M, Alexis MN. New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription. Bioorg Med Chem. 2011Jan 1;19(1):339-51.
  14. Koufaki M, Theodorou E, Alexi X, Alexis MN. Synthesis of a second generation chroman/catechol hybrids and evaluation of their activity in protecting neuronal cells from oxidative stress-induced cell death. Bioorg Med Chem. 2010 Jun 1;18(11):3898-909.
  15. Tchokouaha RF, Alexi X, Chosson E, Besson T, Skaltsounis AL, Seguin E, Alexis MN, Wandji J. Erymildbraedin A and B, two novel cytotoxic dimethylpyrano-isoflavones from the stem bark of Erythrina mildbraedii: evaluation of their activity toward endocrine cancer cells. J Enzyme Inhib Med Chem. 2010 Apr;25(2):228-33.
  16. Koufaki M, Theodorou E, Alexi X, Nikoloudaki F, Alexis MN. Synthesis of tropolone derivatives and evaluation of their in vitro neuroprotective activity. Eur J Med Chem. 2010 Mar;45(3):1107-12.
  17. Calogeropoulou T, Avlonitis N, Minas V, Alexi X, Pantzou A, Charalampopoulos I, Zervou M, Vergou V, Katsanou ES, Lazaridis I, Alexis MN, Gravanis A. Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective activity. J Med Chem. 2009 Nov 12;52(21):6569-87.
  18. Alexi X, Kasiotis KM, Fokialakis N, Lambrinidis G, Meligova AK, Mikros E, Haroutounian SA, Alexis MN. Differential estrogen receptor subtype modulators: assessment of estrogen receptor subtype-binding selectivity and transcription-regulating properties of new cycloalkyl pyrazoles. J Steroid Biochem Mol Biol. 2009 Nov;117(4-5):159-67.
  19. Djiogue S, Halabalaki M, Alexi X, Njamen D, Fomum ZT, Alexis MN, Skaltsounis AL. Isoflavonoids from Erythrina poeppigiana: evaluation of their binding affinity for the estrogen receptor. J Nat Prod. 2009 Sep;72(9):1603-7.
  20. Koufaki M, Kiziridi C, Alexi X, Alexis MN. Design and synthesis of novel neuroprotective 1,2-dithiolane/chroman hybrids. Bioorg Med Chem. 2009 Sep 1;17(17):6432-41.
  21. Ioannou E, Abdel-Razik AF, Alexi X, Vagias C, Alexis MN, Roussis V. 9,11-Secosterols with antiproliferative activity from the gorgonian Eunicella cavolini. Bioorg Med Chem. 2009 Jul 1;17(13):4537-41.
  22. Lagiou P, Samoli E, Lagiou A, Georgila C, Zourna P, Barbouni A, Gkiokas G, Vassilarou D, Tsikkinis A, Sfikas C, Sekeris CE, Hsieh CC, Adami HO, Trichopoulos D. Diet and expression of estrogen alpha and progesterone receptors in the normal mammary gland. Cancer Causes Control. 2009 Jul;20(5):601-7.
  23. Psarra AM, Sekeris CE. Glucocorticoid receptors and other nuclear transcription factors in mitochondria and possible functions. Biochim Biophys Acta. 2009 May;1787(5):431-6. Review.
  24. Lagiou P, Georgila C, Samoli E, Lagiou A, Zourna P, Minaki P, Vassilarou D, Papadiamandis I, Sfikas C, Kalapothaki V, Sekeris CE, Trichopoulos D. Estrogen alpha and progesterone receptor expression in the normal mammary epithelium in relation to breast cancer risk. Int J Cancer. 2009 Jan15;124(2):440-2.
  25. Ioannou E, Abdel-Razik AF, Zervou M, Christofidis D, Alexi X, Vagias C, Alexis MN, Roussis V. 5alpha,8alpha-Epidioxysterols from the gorgonian Eunicella cavolini and the ascidian Trididemnum inarmatum: isolation and evaluation of their antiproliferative activity. Steroids. 2009 Jan;74(1):73-80.
  26. Halabalaki M, Alexi X, Aligiannis N, Alexis MN, Skaltsounis AL. Ebenfurans IV-VIII from Onobrychis ebenoides: Evidence that C-Prenylation is the Key Determinant of the Cytotoxicity of 3-Formyl-2-arylbenzofurans. J Nat Prod. 2008 Nov 6; 71(11):1934-1937.
  27. Psarra AM, Sekeris CE. Steroid and thyroid hormone receptors in mitochondria. IUBMB Life. 2008 Apr;60(4):210-23. Review.
  28. Ioannou E, Abdel-Razik AF, Alexi X, Vagias C, Alexis MN, Roussis V. Pregnanes with antiproliferative activity from the gorgonian Eunicella cavolini. Tetrahedron 2008; 64:11797–11801.
  29. Tenta R, Pitulis N, Tiblalexi D, Consoulas C, Katopodis H, Konstantinidou E, Manoussakis M, Kletsas D, Alexis MN, Poyatzi A, Koutsilieris M. Mechanisms of the action of zoledronic acid on human MG-63 osteosarcoma cells. Horm Metab Res. 2008 Nov;40(11):737-45.
  30. Bakas P, Liapis A, Vlahopoulos S, Giner M, Logotheti S, Creatsas G, Meligova AK, Alexis MN, Zoumpourlis V. Estrogen receptor alpha and beta in uterine fibroids: a basis for altered estrogen responsiveness. Fertil Steril. 2008 Nov;90(5):1878-85.
  31. Psarra AM, Sekeris CE. Nuclear receptors and other nuclear transcription factors in mitochondria: regulatory molecules in a new environment. Biochim Biophys Acta. 2008 Jan;1783(1):1-11.
  32. Koufaki M, Kiziridi C, Nikoloudaki F, Alexis MN. Design and synthesis of 1,2-dithiolane derivatives and evaluation of their neuroprotective activity. Bioorg Med Chem Lett. 2007 Aug 1;17(15):4223-7.
  33. Voutsas IF, Gritzapis AD, Alexis MN, Katsanou ES, Perez S, Baxevanis CN, Papamichail M. A novel quantitative flow cytometric method for measuring glucocorticoid receptor (GR) in cell lines: correlation with the biochemical determination of GR. J Immunol Methods. 2007 Jul 31;324(1-2):110-9.
  34. Skretas G, Meligova AK, Villalonga-Barber C, Mitsiou DJ, Alexis MN, Micha-Screttas M, Steele BR, Screttas CG, Wood DW. Engineered chimeric enzymes as tools for drug discovery: generating reliable bacterial screens for the detection, discovery, and assessment of estrogen receptor modulators. J Am Chem Soc. 2007 Jul 11;129(27):8443-57.
  35. Solakidi S, Psarra AM, Sekeris CE. Differential distribution of glucocorticoid and estrogen receptor isoforms: localization of GRbeta and ERalpha in nucleoli and GRalpha and ERbeta in the mitochondria of human osteosarcoma SaOS-2 and hepatocarcinoma HepG2 cell lines. J Musculoskelet Neuronal Interact. 2007 Jul-Sep;7(3):240-5.
  36. Katsanou ES, Halabalaki M, Aligiannis N, Mitakou S, Skaltsounis AL, Alexi X, Pratsinis H, Alexis MN. Cytotoxic effects of 2-arylbenzofuran phytoestrogens on human cancer cells: modulation by adrenal and gonadal steroids. J Steroid Biochem Mol Biol. 2007 May;104(3-5):228-36.
  37. Lambrinidis G, Halabalaki M, Katsanou ES, Skaltsounis AL, Alexis MN, Mikros E. Environ Chem Lett. 2006; 4:159-174.Review.
  38. Psarra AM, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of regulatory agents involved in neuroimmunomodulation. Ann N Y Acad Sci. 2006 Nov;1088:12-22. Review.
  39. Apostolopoulos V, Pietersz GA, Tsibanis A, Tsikkinis A, Drakaki H, Loveland BE, Piddlesden SJ, Plebanski M, Pouniotis DS, Alexis MN, McKenzie IF, Vassilaros S. Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]. Breast Cancer Res. 2006;8(3):R27.
  40. Halabalaki M, Alexi X, Aligiannis N, Lambrinidis G, Pratsinis H, Florentin I, Mitakou S, Mikros E, Skaltsounis AL, Alexis MN. Estrogenic activity of isoflavonoids from Onobrychis ebenoides. Planta Med. 2006 May;72(6):488-93.
  41. Kasiotis KM, Mendorou C, Haroutounian SA, Alexis MN. High affinity 17alpha-substituted estradiol derivatives: synthesis and evaluation of estrogen receptor agonist activity. Steroids. 2006 Mar;71(3):249-55.
  42. Psarra AM, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Mol Cell Endocrinol. 2006 Feb 26;246(1-2):21-33. Review.
  43. Roberts ML, Drosopoulos KG, Vasileiou I, Stricker M, Taoufik E, Maercker C, Guialis A, Alexis MN, Pintzas A. Microarray analysis of the differential transformation mediated by Kirsten and Harvey Ras oncogenes in a human colorectal adenocarcinoma cell line. Int J Cancer. 2006 Feb 1;118(3):616-27.
  44. Koufaki M, Theodorou E, Galaris D, Nousis L, Katsanou ES, Alexis MN. Chroman/catechol hybrids: synthesis and evaluation of their activity against oxidative stress induced cellular damage. J Med Chem. 2006 Jan 12;49(1):300-6.
  45. Solakidi S, Psarra AM, Nikolaropoulos S, Sekeris CE. Estrogen receptors alpha and beta (ERalpha and ERbeta) and androgen receptor (AR) in human sperm: localization of ERbeta and AR in mitochondria of the midpiece. Hum Reprod. 2005 Dec;20(12):3481-7.
  46. Psarra AM, Solakidi S, Trougakos IP, Margaritis LH, Spyrou G, Sekeris CE. Glucocorticoid receptor isoforms in human hepatocarcinoma HepG2 and SaOS-2 osteosarcoma cells: presence of glucocorticoid receptor alpha in mitochondria and of glucocorticoid receptor beta in nucleoli. Int J Biochem Cell Biol. 2005 Dec;37(12):2544-58.
  47. Solakidi S, Psarra AM, Sekeris CE. Differential subcellular distribution of estrogen receptor isoforms: localization of ERalpha in the nucleoli and ERbeta in the mitochondria of human osteosarcoma SaOS-2 and hepatocarcinoma HepG2 cell lines. Biochim Biophys Acta. 2005 Sep 30;1745(3):382-92.
  48. Mitsiou DJ, Florentin I, Baki L, Georgakopoulos A, Alexis MN. Pronounced enhancement of glucocorticoid-induced gene expression following severe heat shock of heat-conditioned cells hints to intricate cell survival tactics. J Steroid Biochem Mol Biol. 2005 Feb;94(1-3):209-17.
  49. Siriani D, Mitsiou DJ, Alexis MN. Heat-induced degradation of overexpressed glucocorticoid receptor Separate protective roles of hsp90 and hsp70. J Steroid Biochem Mol Biol. 2005 Feb;94(1-3):93-101.

Active Patents:

  1. Alexis MN, Dimolea E, Florentin I, Pechtelidou A and Sekeris CE. Monoclonal and polyclonal antibodies to glucococorticoid and estrogen receptors as immunodiagnostics for cancer prognosis. Ο.Β.Ι. 1005417
  2. Micha-Screttas M, Steele BR, Villalonga-Barber C, Alexis MN. New substituted stilbenoid derivatives with meuroprotective activity. O.B.I. 1005435
  3. Alexis MN, Papahatjis D, Sekeris CE, Assimomitis N, Siriani D. Tissue specific antiestrogens selective for estrogen receptor alpha. Ο.Β.Ι. 1005694
  4. Gravanis A, Calogeropouloy T, Kastanas E, Margioris A, Charalambopoulos I, Avlonitis N, Minas V, Alexaki VI, Tsatsanis C, Alexis MN, Remboutsika E, Vergou B, Neophytou C. Neurosteroid compounds. PCT patent application W02008155534 and patent applications to UK (GB20070011948), Australia (AU2008265046), Canada (2691071), Korea (KR20100040292), Japan (JP2010530404), EPO (EP2158209), Eurasian Patent Office (EA018632 B1), China (CN101784558) and USA (US2010234335).
  5. Calogeropoulou T, Alexis MN, Koini E, Avlonitis N, Alexi X. 1,4-Benzoxazine Derivatives. O.B.I. O.B.I. 1007084.

Competitively funded Projects (2005- ):

  1. Research Funding Program KRIPIS: Project STHENOS: "Targeted therapeutic approaches against ageing and degenerative diseases, cancer in particular", 2013-2015.
  2. Research Funding Program THALES: Project 80038: "Development of new selective estrogen receptor modulators for preventing menopause consequences (SERMENCO)", 2012-2015.
  3. Research Funding Program THALES: Project 85355: "Molecular sub-typing of Triple Negative Breast Cancer (TNBC)", 2012-2015.
  4. National action 'Cooperation' – Sub-action Ι: Medium & Small Scale Cooperative Projects: "Development of natural products and analogues for osteoporosis prevention: transcriptomic, proteomic and metabolomic approaches (OSTEOPRO)", 09ΣΥΝ-11-1076, 2011-2014.
  5. National action 'Cooperation' – Sub-action ΙΙ: Large Scale Cooperative Projects: "PIK3CA Oncogenic Mutations in Breast and Colon Cancers: Development of Targeted Anticancer Drugs and Diagnostics (POM)", 09ΣΥΝ-11-675, 2010-2014.
  6. EU Initial Training Network (ITN), ''A European Research Training Site for the Design and Synthesis of Novel Neuroprotective and Hypoglycaemic Agents through a Multi-disciplinary approach'', MTKD-CT-2006-020575, 2006-2010.
  7. EU Network of Excellence "ECNIS – Environmental Cancer risks, Nutrition and Individual Susceptibility', FOOD-CT-2005-513943, 2005-2010.
  8. Greek Framework Programme Competitiveness- Research Network PENED, "In search of a role for estrogen receptor beta in breast cancer", 03ΕΔ644, 2006-2009.
  9. EU Transfer of Knowledge (TOK) Program, "Macromolecular assemblies involved in regulated gene expression", MTKD-CT-2004-509836, 2004-2008.
  10. Greek Framework Program Competitiveness - Research Network DSBEPRO, "Assessment of the estrogenic activity of natural compounds and derivatives thereof", 02DSBEPRO32, 2006-2008.
  11. Greek Framework Program Competitiveness - Research Network EUREKA, "Novel Selective Estrogen Receptor Modulators: Synthesis and evaluation of biological activities", EUREKA Ε!3060-SERMS, 2004-2007.
  12. Greek Framework Program Competitiveness- Research Network PENED, ''Neurosteroids; Investigation of the mechanism of action of neurosteroids as neuroprotective agents; Development of new neurosteroids of high neuroprotective and marginal hormonal activity'', 01ΕΔ258, 2002-06.
  13. Greek Framework Program Competitiveness - funding scheme PRAKSE, "Tissue-specific antiestrogens", 02PRAKSE97, 2003-2005.
  14. Greek Framework Program Competitiveness - funding scheme PRAKSE, "Immunodiagnostics for breast cancer prognosis", 02PRAKSE98, 2003-2005.
  15. Greek Framework Program Competitiveness - research network PAVET, "Immunochemical tools for breast cancer prognosis", PAVET2000-00BE199, 2001-2004.
  16. EU Marie Curie Development Host (HD) Research Program, "Regulation of transcription and mRNA processing by oncogenic signals", HPMD-CT-2001-00116, 2002-2005.

 

 

 
 

 

 
 

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