Savvas Christoforidis
Our group studies the interplay between endocytosis, signaling and exocytosis in endothelial cells and the role they play in vascular physiology.
Activated endothelial cells and/or endothelial dysfunction are implicated in the most life-threatening diseases, such as cardiovascular and inflammatory diseases as well as in cancer-angiogenesis. Intriguingly, key vasoactive players of the above pathophysiological processes are stored in specific granules (called Weibel Palade bodies) in endothelial cells. Upon activation of receptors at the cell surface of endothelial cells, Weibel Palade bodies fuse with plasma membrane and release their vasoactive molecules in the blood stream.
Our studies have the following aims:
1. To shed light on the molecular mechanisms that are responsible for Weibel Palade body trafficking and exocytosis.
2. To identify the cell surface receptors and the corresponding signaling cascades that trigger Weibel Palade body exocytosis.
3. To track the endocytic routes followed by activated receptors of endothelial cells and the role of these routes in signaling and Weibel Palade body exocytosis.
4. To get functional insights into the role of the above processes in vascular physiology and in serious vascular diseases.
These studies will shed light on the molecular and functional links between secretion, endocytosis and signalling, as well as on their spatial and temporal coordination. Ultimately, the knowledge generated by these studies will contribute to the design of more effective therapeutic approaches for vascular diseases.
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