Σάββας Χριστοφορίδης
Η ομάδα μας μελετά τις αλληλεπιδράσεις μεταξύ ενδοκυττάρωσης, μεταγωγής σήματος και εξωκυττάρωσης στα ενδοθηλιακά κύτταρα και το ρόλου που διαδραματίζουν στη φυσιολογία των αιμοφόρων αγγείων.
Τα ενεργοποιημένα ενδοθηλιακά κύτταρα και η δυσλειτουργία του ενδοθηλίου εμπλέκονται στις πιο απειλητικές ασθένειες, όπως τα καρδιαγγειακά και φλεγμονώδη νοσήματα και στην αγγειογένεση των καρκινικών όγκων. Είναι αξιοσημείωτο το γεγονός ότι πολύ σημαντικά αγγειοδραστικά μόρια που ελέγχουν τις παραπάνω παθοφυσιολογικές διαδικασίες βρίσκονται αποθηκευμένα σε ειδικά αποθηκευτικά οργανίδια (που ονομάζονται σωμάτια Weibel Palade) των ενδοθηλιακών κυττάρων. H ενεργοποίηση υποδοχέων στην επιφάνεια των ενδοθηλιακών κυττάρων επάγει τη σύντηξη των σωμάτιων Weibel Palade με την κυτταρική μεμβράνη και την απελευθέρωση των αγγειοδραστικών μορίων τους στην κυκλοφορία του αίματος.
Η μελέτες της ομάδας μας έχουν τους εξής στόχους:
1. Να διαλευκάνουμε τους μοριακούς μηχανισμούς που είναι υπεύθυνοι για την μετακίνηση και εξωκυττάρωση των σωμάτιων WeibelPalade.
2. Να ταυτοποιήσουμε τους υποδοχείς της μεμβράνης και τα καθοδικά σηματοδοτικά μόρια που επάγουν την έκκριση των σωμάτιων WeibelPalade.
3. Να ιχνηλατήσουμε τα μονοπάτια ενδοκυττάρωσης των ενεργοποιημένων υποδοχέων των ενδοθηλιακών κυττάρων και το ρόλο των μονοπατιών αυτών στην μεταγωγή του σήματος και την έκκριση των σωμάτιων WeibelPalade.
4. Να διερευνήσουμε τη λειτουργική σημασία των παραπάνω διαδικασιών στη φυσιολογία των αγγείων και σε σοβαρές ασθένειες των αγγείων.
Basagiannis D, Zografou S, Goula E, Gkeka D, Kolettas E, Christoforidis S. (2021) Chemical Inhibitors of Dynamin Exert Differential Effects in VEGF Signaling. Cells. 10:997.
Basagiannis D, Zografou S, Galanopoulou K, Christoforidis S. (2017) Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner. Sci Rep. 7:45035.
Basagiannis D, Zografou S, Murphy C, Fotsis T, Morbidelli L, Ziche M, Bleck C, Mercer J, Christoforidis S. (2016) VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation via macropinocytosis. J Cell Sci. 129:4091-4104.
Zografou S, Basagiannis D, Papafotika A, Shirakawa R, Horiuchi H, Auerbach D, Fukuda M, Christoforidis S. (2012) A complete Rab screening reveals novel insights in Weibel-Palade body exocytosis. J Cell Sci. 125:4780-4790.
Christoforidis S, McBride H, Burgoyne R, Zerial M. (1999) The Rab5 effector EEA1 is a core component of endosome docking. Nature 397:621-627.
Basagiannis D, Zografou S, Goula E, Gkeka D, Kolettas E, Christoforidis S. (2021) Chemical Inhibitors of Dynamin Exert Differential Effects in VEGF Signaling. Cells. Apr 23;10(5):997. doi: 10.3390/cells10050997. PMID: 33922806.
Basagiannis D, Zografou S, Galanopoulou K, Christoforidis S. (2017) Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner. Sci Rep. 2017 Mar 22;7:45035. doi: 10.1038/srep45035.
Martzoukou O, Amillis S, Zervakou A, Christoforidis S, Diallinas G. (2017) The AP-2 complex has a specialized clathrin-independent role in apical endocytosis and polar growth in fungi. Elife. Feb 21;6. pii: e20083. doi: 10.7554/eLife.20083.
Argyros O, Lougiakis N, Kouvari E, Papafotika A, Raptopoulou CP, Psycharis V, Christoforidis S, Pouli N, Marakos P, Tamvakopoulos C. (2017) Design and synthesis of novel 7-aminosubstituted pyrido[2,3-b]pyrazines exhibiting anti-breast cancer activity. Eur J Med Chem. Jan 27;126:954-968. doi: 10.1016/j.ejmech.2016.12.025
Daniilides K, Lougiakis N, Evangelidis T, Kostakis IK, Pouli N, Marakos P, Mikros E, Skaltsounis AL, Bach S, Baratte B, Ruchaud S, Karamani V, Papafotika A, Christoforidis S, Argyros O, Kouvari E, Tamvakopoulos C. (2017) Discovery of new aminosubstituted pyrrolopyrimidines with antiproliferative activity against breast cancer cells and investigation of their effect towards the PI3Kα enzyme. Anticancer Agents Med Chem. 2016 Dec 7. [Epub ahead of print] PMID: 27928955
Basagiannis D, Zografou S, Murphy C, Fotsis T, Morbidelli L, Ziche M, Bleck C, Mercer J, Christoforidis S. (2016) VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation via macropinocytosis. J Cell Sci, 129(21):4091-4104
Basagiannis D, Christoforidis S. (2016) Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding. J Biol Chem. 291, 16892-903
Tsolis KC, Bagli E, Kanaki K, Zografou S, Carpentier S, Bei ES, Christoforidis S, Zervakis M, Murphy C, Fotsis T, Economou A. (2016) Proteome Changes during Transition from Human Embryonic to Vascular Progenitor Cells. J Proteome Res. 2016 Jun 3;15(6):1995-2007. doi: 10.1021/acs.jproteome.6b00180.
Kitsiouli E, Antoniou G, Gotzou H, Karagiannopoulos M, Basagiannis D, Christoforidis S, Nakos G, Lekka ME. (2015) Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells. Biochim Biophys Acta. 2015 Jul;1852(7):1288-97. doi: 10.1016/j.bbadis.2015.03.008.
Gkeka P, Evangelidis T, Pavlaki M, Lazani V, Christoforidis S, Agianian B, and Cournia Z (2014) Investigating the structure and dynamics of the PIK3CA wild-type and H1047R oncogenic mutant. PLoS Comput Biol, 10(10), e1003895
Gkeka P, Papafotika A, Christoforidis S, and Cournia Z (2014) Exploring a non-ATP pocket for potential allosteric modulation of PI3Kα. J Phys Chem B, 119(3), 1002-1016
Zografou S, Basagiannis D, Papafotika A, Shirakawa R, Horiuchi H, Auerbach D, Fukuda M, and Christoforidis S (2012) A complete Rab screening reveals novel insights in Weibel-Palade body exocytosis. J Cell Sci, 125, 4780-4790
Sfikas A, Batsi C, Tselikou E, Vartholomatos G, Monokrousos N, Pappas P, Christoforidis S, Tzavaras T, Kanavaros P, Gorgoulis VG, Marcu KB, and Kolettas E (2012) The canonical NF-κB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage. Cell Signal, Nov;24(11):2007-23
Papanikolaou A, Papafotika Α, and Christoforidis S, (2011) CD39 reveals novel insights into the role of transmembrane domains in protein processing, apical targeting and activity. Traffic, 12(9):1148-1165
Boleti H, Smirlis D, Dalagiorgou G, Meurs EF, Christoforidis S, and Mavromara P, (2010) ER targeting and retention of the HCV NS4B protein relies on the concerted action of multiple structural features including its transmembrane domains. Mol Membr Biol, 27(1):45-62
Batsi C, Markopoulou S, Kontargiris E, Charalambous C, Thomas C, Christoforidis S, Kanavaros P, Constantinou AI, Marcu KB, and Kolettas, E (2009) Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27Kip1-dependent G1/S cell cycle arrest in conjunction with NF-kB activation. Biochem Pharmacol, 78(1):33-44
Shin HW, Hayashi M, Christoforidis S, Lacas-Gervais S, Hoepfner S, Wenk MR, Modregger J, Uttenweiler-Joseph S, Wilm M, Nystuen A, Frankel WN, Solimena M, De Camilli P, and Zerial M (2005) An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. J Cell Biol, 170(4):607-18
Papanikolaou Α, Papafotika Α, Murphy C, Papamarcaki T, Tsolas O, Drab M, Kurzchalia TV, Kasper M, and Christoforidis S (2005) Cholesterol-dependent lipid assemblies regulate the activity of the ecto-nucleotidase CD39. J Biol Chem, 280(28):26406-14
Karetsou Z, Martic G, Tavoulari S, Christoforidis S, Wilm M, Gruss C, Papamarcaki T (2004) Prothymosin alpha associates with the oncoprotein SET and is involved in chromatin decondensation. FEBS Lett, 577, 496-500
Schnatwinkel C, Christoforidis S, Lindsay MR, Uttenweiler-Joseph S, Wilm M, Parton RG, and Zerial M (2004) The rab5 effector rabankyrin-5 regulates and coordinates different endocytic mechanisms. PLoS Biol, 2, 1363-1380
Miaczynska M, Christoforidis S, Giner A, Shevchenko A, Uttenweiler-Joseph S, Habermann B, Wilm M, Parton RG, and Zerial, M (2004) APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell, 116, 445-56
Doulias PT, Christoforidis S, Brunk UT, and Galaris D (2003) Endosomal and lysosomal effects of desferrioxamine: protection of HeLa cells from hydrogen peroxide-induced DNA damage and induction of cell-cycle arrest. Free Radic Biol Med, 35, 719-728
Uttenweiler-Joseph S, Neubauer G, Christoforidis S, Zerial M, and Wilm M (2001) Automated de novo sequencing of proteins using the differential scanning technique. Proteomics, 1(5), 668-82
Christoforidis S, and Zerial M (2001) Purification of EEA1 from bovine brain cytosol using a Rab5 affinity chromatography and functional test in an in vitro endosome fusion assay. Methods Enzymol, 329,120-132
Lanzetti L, Rybin V, Malabarba MG, Christoforidis S, Scita G, Zerial M, and Di Fiore PP (2000) The EPS8 protein coordinates EGF receptor signaling through Rac and trafficking through Rab5. Nature, 408, 374-377
Nielsen E, Christoforidis S, Uttenweiler-Joseph S, Giner A, Wilm M, Hoflack B, and Zerial M (2000) Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain. J Cell Biol, 151, 601-612
Christoforidis S, and Zerial M (2000) Purification and Identification of Novel Rab Effectors using Affinity Chromatography. Methods, 20, 403-410
Christoforidis, S, Miaczynska, M, Ashman, K, Wilm, M, Zhao, L, Yip, A-C, Waterfield, MD, Backer, JM, and Zerial, M (1999) Phosphoinositide-3-Kinases are Rab5 effectors. Nature Cell Biol, 1, 249-252
Christoforidis S, McBride H, Burgoyne R and Zerial M (1999) The Rab5 effector EEA1 is a core component of endosome docking. Nature, 397, 621-627
Simonsen A, Lippe R, Christoforidis S, Gaullier JM, Brech A, Callaghan J, Toh BH, Murphy C, Zerial M, and Stenmark H (1998) EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature, 394, 494-498
Vitale G, Rybin V, Christoforidis S, Thornqvist P, McCaffrey M, Stenmark H, and Zerial M (1998) Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound rab4 and rab5. EMBO J, 17, 1941-1951
Christoforidis S, Papamarcaki T, and Tsolas O (1996) Human placental ATP diphosphohydrolase is a highly N-glycosylated plasma membrane enzyme. Biochim Biophys Acta, 1282, 257-262
Christoforidis S, Papamarcaki T, Galaris D, Kellner R, and Tsolas O (1995) Purification and properties of human placental ATP diphosphohydrolase. Eur J Biochem, 234, 66-74