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Dimitris Kardassis

Dimitris Kardassis

IMBB Group Leader (Full Professor, Univ. of Crete)
Email address
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Phone
+30-2810-394549
Fax
+30-2810-394530
Lab web page

Cardiovascular disease (CVD) is the leading cause of death in Western societies. Genetic defects in key genes of lipoprotein metabolism and pathological conditions such as chronic inflammation, diabetes, obesity and the metabolic syndrome contribute to the pathogenesis of atherosclerosis, which is the underlying cause of CVD.
The focus of our research is on the genetic basis and the molecular mechanisms of atherosclerosis.
More specifically, we are interested in:
a) Understanding the mechanisms that control the expression of key genes of High Density Lipoproteins (HDL) metabolism in the liver, epithelial cells and macrophages under basal or inflammatory conditions.
b) Understanding how the structure and the functions of HDL are affected by inflammation using animal models of arthritis and IBD
c) Identifying novel genes of HDL metabolism and novel HDL-based biomarkers
d) Developing novel humanized mouse models of dyslipidemias
e) Characterizing natural mutations in the coding regions and the promoters of HDL genes in patients with increased risk for ischemia and myocardial infarction
f) Studying the molecular and genetic basis of the metabolic syndrome using systems biology approaches

Our research is funded by the EU fp7 HEALTH program and the Ministries of Education and Development of Hellas (Synergasia, Thalis, Heraklitos)

Duka A, Fotakis P, Georgiadou D, Kateifides A, Tzavlaki K, von Eckardstein L, Stratikos E, Kardassis D, Zannis VI. (2013) ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT. J Lipid Res. 54:107-15.

Trusca VG, Florea IC, Kardassis D, Gafencu AV. (2012) STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages. PLoS One 7:e40463.

Ohnsorg PM, Rohrer L, Perisa D, Kateifides A, Chroni A, Kardassis D, Zannis VI, von Eckardstein A. (2011) Carboxyl Terminus of Apolipoprotein A-I (ApoA-I) Is Necessary for the Transport of Lipid-free ApoA-I but Not Prelipidated ApoA-I Particles through Aortic Endothelial Cells. J Biol Chem. 286:7744-54.

Mosialou I, Krasagakis K, Kardassis D. (2011) Opposite regulation of the human apolipoprotein M gene by Hepatocyte Nuclear Factor 1 and Jun transcription factors. J Biol Chem. 286:17259-69.

Mosialou I, Zannis VI, Kardassis D. (2010) Regulation of human apolipoprotein Μ gene expression by orphan and ligand-dependent nuclear receptors. J Biol Chem. 285: 30719-30.

Kanaki M, Tiniakou I, Thymiakou E, Kardassis D. (2017) Physical and functional interactions between nuclear receptor LXRα and the forkhead box transcription factor FOXA2 regulate the response of the human lipoprotein lipase gene to oxysterols in hepatic cells. Biochim Biophys Acta. 1860(8):848-860. 

Trusca VG, Fuior EV, Fenyo IM, Kardassis D, Simionescu M, Gafencu AV. (2017) Differential action of glucocorticoids on apolipoprotein E gene expression in macrophages and hepatocytes. PLoS One. 12(3):e0174078. 

Kanaki M, Kardassis D. (2017) Regulation of the human lipoprotein lipase gene by the forkhead box transcription factor FOXA2/HNF-3β in hepatic cells. Biochim Biophys Acta. 1860(3):327-336. 

Latsoudis H, Mashreghi MF, Grün JR, Chang HD, Stuhlmüller B, Repa A, Gergiannaki I, Kabouraki E, Vlachos GS, Häupl T, Radbruch A, Sidiropoulos P, Doukoumetzidis K, Kardassis D, Niewold TB, Boumpas DT, Goulielmos GN. (2017) Differential Expression of miR-4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF). J Cell Physiol. 232(6):1326-1336. 

Myrthianou E, Zervou MI, Budu-Aggrey A, Eliopoulos E, Kardassis D, Boumpas DT, Kougkas N, Barton A, Sidiropoulos P, Goulielmos GN.(2017) Investigation of the genetic overlap between rheumatoid arthritis and psoriatic arthritis in a Greek population. Scand J Rheumatol. 46(3):180-186. 

Theofilatos D, Anestis A, Hashimoto K, Kardassis D. Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α. Biochem Biophys Res Commun. 469(3):573-9. 

Stavri S, Simionescu M, Kardassis D, Gafencu AV. (2015) Krüppel-like factor 4 synergizes with CREB to increase the activity of apolipoprotein E gene promoter in macrophages. Biochem Biophys Res Commun. 468(1-2):66-72. 

Roman C, Fuior EV, Trusca VG, Kardassis D, Simionescu M, Gafencu AV. (2015) Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes. Biochem Biophys Res Commun. 468(1-2):190-5. 

Tiniakou I, Kanaki Z, Georgopoulos S, Chroni A, Van Eck M, Fotakis P, Zannis VI, Kardassis D. (2015) Natural human apoA-I mutations L141RPisa and L159RFIN alter HDL structure and functionality and promote atherosclerosis development in mice. Atherosclerosis. 243(1):77-85. 

Gkouskou KK, Ioannou M, Pavlopoulos GA, Georgila K, Siganou A, Nikolaidis G, Kanellis DC, Moore S, Papadakis KA, Kardassis D, Iliopoulos I, McDyer FA, Drakos E, Eliopoulos AG. (2016) Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis. Oncogene. 35(19):2496-505. 

Gkolfinopoulou C, Stratikos E, Theofilatos D, Kardassis D, Voulgari PV, Drosos AA, Chroni A. (2015) Impaired Antiatherogenic Functions of High-density Lipoprotein in Patients with Ankylosing Spondylitis. J Rheumatol. 42(9):1652-60. 

Fotakis P, Kuivenhoven JA, Dafnis E, Kardassis D, Zannis VI. (2015) The Effect of Natural LCAT Mutations on the Biogenesis of HDL. Biochemistry. 54(21):3348-59. 

Tiniakou I, Drakos E, Sinatkas V, Van Eck M, Zannis VI, Boumpas D, Verginis P, Kardassis D. (2015) High-density lipoprotein attenuates Th1 and th17 autoimmune responses by modulating dendritic cell maturation and function. J Immunol. 194(10):4676-87. 

Kardassis D, Gafencu A, Zannis VI, Davalos A. (2015) Regulation of HDL genes: transcriptional, posttranscriptional, and posttranslational. Handb Exp Pharmacol. 224:113-79. 

Zannis VI, Fotakis P, Koukos G, Kardassis D, Ehnholm C, Jauhiainen M, Chroni A. (2015) HDL biogenesis, remodeling, and catabolism. Handb Exp Pharmacol. 224:53-111. 

Fotakis P, Kuivenhoven JA, Dafnis E, Kardassis D, Zannis VI. (2015) The Effect of Natural LCAT Mutations on the Biogenesis of HDL, Biochemistry. 54(21):3348-59. 

Tiniakou I, Drakos E, Sinatkas V, Van Eck M, Zannis VI, Boumpas D, Verginis P, Kardassis D. (2015) High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function. Journal Of Immunology. 15;194(10):4676-87. 

Fotakis, P; Vezeridis, A; Dafnis, I; Chroni, A; Kardassis, D; Zannis, VI. (2014) apoE3[K146N/R147W] acts as a dominant negative apoE form that prevents remnant clearance and inhibits the biogenesis of HDL. Journal Of Lipid Research, 55(7): 1310-1323. 

Thymiakou, E; Kardassis, D. (2014) Novel mechanism of transcriptional repression of the human ATP binding cassette transporter A1 gene in hepatic cells by the winged helix/forkhead box transcription factor A2. Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms, 1839(6): 526-536. 

Kardassis, D; Mosialou, I; Kanaki, M; Tiniakou, I; Thymiakou, E. (2014) Metabolism of HDL and its Regulation. Current Medicinal Chemistry, 21(25): 2864-2880. 

Papadakis G, Tsortos A, Kordas A, Tiniakou I, Morou E, Vontas J, Kardassis D, Gizeli E. (2013) Acoustic detection of DNA conformation in genetic assays combined with PCR. Scientific Reports, 3:2033. 

Trusca VG, Florea IC, Kardassis D, Gafencu AV. (2012) STAT1 interacts with RXRα to upregulate ApoCII gene expression in macrophages. PLoS One. 7(7):e40463 

Stagakis I, Bertsias G, Karvounaris S, Kavousanaki M, Virla D, Raptopoulou A, Kardassis D, Boumpas DT, Sidiropoulos PI. (2012) Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Research & Therapy, Volume: 14  Issue: 3, Article Number: R141. 

Mosialou I, Krasagakis K, Kardassis D. (20111) Opposite Regulation of the Human Apolipoprotein M Gene by Hepatocyte Nuclear Factor 1 and Jun Transcription Factors. Journal Of Biological Chemistry, 286(19): 17259-17269. 

Trusca VG, Fuior EV, Florea IC, Kardassis D, Simionescu M, Gafencu AV. (2011) Macrophage-specific Up-regulation of Apolipoprotein E Gene Expression by STAT1 Is Achieved via Long Range Genomic Interactions. Journal Of Biological Chemistry, 286(16): 13891-13904. 

Ohnsorg PM, Rohrer L, Perisa D, Kateifides A, Chroni A, Kardassis D, Zannis VI, von Eckardstein A. (2011) Carboxyl Terminus of Apolipoprotein A-I (ApoA-I) Is Necessary for the Transport of Lipid-free ApoA-I but Not Prelipidated ApoA-I Particles through Aortic Endothelial Cells, Journal Of Biological Chemistry, 286(10): 7744-7754. 

Goulielmos GN, Petraki E, Vassou D, Eliopoulos E, Iliopoulos D, Sidiropoulos P, Aksentijevich I, Kardassis D, Boumpas DT. (2010) The role of the pro-apoptotic protein Siva in the pathogenesis of Familial Mediterranean fever: A structural and functional analysis. Biochemical And Biophysical Research Communications, 402(1): 141-146. 

Mosialou I, Zannis VI, Kardassis D. (2010) Regulation of Human Apolipoprotein M Gene Expression by Orphan and Ligand-dependent Nuclear Receptors. Journal Of Biological Chemistry, 285(40): 30719-30730. 

Mavridou S, Venihaki M, Rassouli O, Tsatsanis C, Kardassis D. (2010) Feedback Inhibition of Human Scavenger Receptor Class B Type I Gene Expression by Glucocorticoid in Adrenal and Ovarian Cells. Endocrinology, 151(7): 3214-3224. 

Tsao T, Kornblau S, Safe S, Watt JC, Ruvolo V, Chen WJ, Qiu YH, Coombes KR, Ju ZL, Abdelrahim M, Schober W, Ling XY, Kardassis D, Meyer C, Schimmer A, Kantarjian H, Andreeff M, Konopleva M. (2010) Role of Peroxisome Proliferator-Activated Receptor-gamma and Its Coactivator DRIP205 in Cellular Responses to CDDO (RTA-401) in Acute Myelogenous Leukemia. Cancer Research, 70(12): 4949-4960. 

Vasilaki E, Papadimitriou E, Tajadura V, Ridley AJ, Stournaras C, Kardassis D. (2010) Transcriptional regulation of the small GTPase RhoB gene by TGF beta-induced signaling pathways, FASEB Journal, 24(3): 891-905. 

Vasilaki E, Siderakis M, Papakosta P, Skourti-Stathaki K, Mavridou S, Kardassis D. (2009) Novel Regulation of Smad3 Oligomerization and DNA Binding by Its Linker Domain. Biochemistry, 48(35): 8366-8378, SEP 8 2009, DOI: 10.1021/bi9005489 

Kardassis D, Murphy C, Fotsis T, Moustakas A, Stournaras C. (2009) “Control of transforming growth factor beta signal transduction by small GTPases”. FEBS Journal, 276(11): 2947-2965.

Akoumianaki T, Kardassis D, Polioudaki H, Georgatos SD, Theodoropoulos PA. (2009) Nucleocytoplasmic shuttling of soluble tubulin in mammalian cells. Journal Of Cell Science, 122(8): 1111-1118. 

Bertsias GK, Nakou M, Choulaki C, Raptopoulou A, Papadimitraki E, Goulielmos G, Kritikos H, Sidiropoulos P, Tzardi M, Kardassis D, Mamalaki C, Boumpas DT. (2009) Genetic, Immunologic, and Immunohistochemical Analysis of the Programmed Death 1/Programmed Death Ligand 1 Pathway in Human Systemic Lupus Erythematosus, Arthritis And Rheumatism, 60(1): 207-218. 

Moschonas A, Kouraki M, Knox PG, Thymiakou E, Kardassis D, Eliopoulos AG. (2008) CD40 induces antigen transporter and immunoproteasome gene expression in carcinomas via the coordinated action of NF-kappa B and of NF-kappa B-mediated de novo synthesis of IRF-1. Molecular And Cellular Biology, 28(20): 6208-6222. 

 

Vardouli L, Vasilaki E, Papadimitriou E, Kardassis D, Stournaras C. (2008) A novel mechanism of TGF beta-induced actin reorganization mediated by Smad proteins and Rho GTPases. FEBS Journal, 275(16): 4074-4087.

Stavroulaki, M., Kardassis, D., Chatzaki, E., Sakellaris, G., Lindschau, C., Haller, H., Tosca, A. and Krasagakis, K. (2008) Exposure of normal human melanocytes to a tumor promoting phorbol ester reverses growth suppression by transforming growth factor beta. J Cell Physiol. 214(2):363-70.

Minoo , P ., Hu , L ., Zhu , N ., Borok , Z ., Bellusci , S ., Groffen , J ., Kardassis , D . and Li , C . (2008) SMAD3 prevents binding of NKX2.1 and FOXA1 to the SpB promoter through its MH1 and MH2 domains. Nucleic Acids Res. 36(1):179-88.

Prokova , V . , Mavridou, S., Papakosta, P., Petratos, K. and Kardassis, D. (2007) Novel mutations in Smad proteins that inhibit signaling by the transforming growth factor beta in mammalian cells. Biochemistry. 46(48):13775-86.

Thymiakou, E., Zannis, V.I. and Kardassis, D. (2007) Physical and functional interactions between liver X receptor/retinoid X receptor and Sp1 modulate the transcriptional induction of the human ATP binding cassette transporter A1 gene by oxysterols and retinoids. Biochemistry 46(41):11473-83.

Psifogeorgou, K., Papakosta, P., Russo, S.J., Neve, R.L., Kardassis, D., Gold, S.J. and Zachariou, V. (2007) RGS9-2 is a negative modulator of mu-opioid receptor function. J Neurochem. 103(2):617-25.

Koukos, G., Chroni, A., Duka, A., Kardassis, D. and Zannis, V.I. (2007) LCAT can rescue the abnormal phenotype produced by the natural ApoA-I mutations (Leu141Arg) Pisa and Leu159Arg)FIN. Biochemistry. 46(37):10713-21.

Koukos, G., Chroni, A., Duka, A., Kardassis, D. and Zannis, V.I. (2007) Naturally occurring and bioengineered apoA-I mutations that inhibit the conversion of discoidal to spherical HDL: the abnormal HDL phenotypes can be corrected by treatment with LCAT. Biochem J. 406(1):167-74.

Drosatos, K., Sanoudou, D., Kypreos, K.E., Kardassis, D. and Zannis, V.I. (2007) A dominant negative form of the transcription factor c-Jun affects genes that have opposing effects on lipid homeostasis in mice. J Biol Chem. 282(27):19556-64.

Gafencu, A.V., Robciuc, M.R., Fuior, E., Zannis, V.I., Kardassis, D. and Simionescu, M. (2007) Inflammatory signaling pathways regulating ApoE gene expression in macrophages. J Biol Chem. 282, 21776-21785.

Nikolaidou-Neokosmidou V, Zannis VI, Kardassis D. (2006) Inhibition of hepatocyte nuclear factor 4 transcriptional activity by the nuclear factor kappaB pathway. Biochem J. 398, 439-450.

Prokova, P., Mavridou, S., Papakosta, P. And Kardassis, D. (2005) Cracterization of a ovel transactivation domain in the Transforming Growth Factor β regulated Smad3 protein. Nucl Acids Res. 33, 3708-3721

Koutsodontis, G., Vasilaki, E., Cou, W.C., Papakosta, P. and Kardassis, D. (2005) Physical and functional interactions between members of the tumor suppressor p53 and the Sp families of transcription factors: Importance for the regulation of genes involved in cell cycle arrest and apoptosis. Biochem. J. 389, 443-455.

Koutsodontis, G. and Kardassis, D., (2004) Inhibition of p53-mediated transcriptional responses by Mithramycin A. Oncogene. 23, 9190-200.

Chou, C., Prokova, V., Shiraishi, K., Valcourt, U., Moustakas, A., Hadzopoulou-Cladaras, M., Zannis, V and Kardassis D. (2003) Smad proteins co-activate hepatocyte nuclear factor 4 by interacting with multiple domains and enhance hepatic gene transcription. Mol Biol Cell 14, 1279-1294.

Prokova V, Mosialos G, Kardassis D. (2002) Inhibition of transforming growth factor β signaling and Smad-dependent activation of transcription by the latent membrane protein 1 of Epstein Barr Virus. J Biol Chem. 277(11):9342-50

Koutsodontis G, Tentes I, Papakosta P, Moustakas A, Kardassis D. (2001) Sp1 plays a critical role in the transcriptional activation of the human cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene by the p53 tumor suppressor protein.
J Biol Chem. 276, 29116-25.

Pardali, K., Kurisaki, A., Moren A., ten Dijke, P., Kardassis, D. and Moustakas, A. (2000) Role of Smad proteins and transcription factor Sp1 in p21/WAF1/Cip1 regulation by Transforming Growth Factor β. J Biol Chem. 275, 29244-56.

Kardassis, D., Pardali, K. and Zannis, V. (2000) SMAD proteins transactivate the human apoC-III promoter by interacting physically and functionally with Hepatocyte Nuclear Factor 4. J. Biol. Chem. 275, 41405-14.

Kardassis, D, Papakosta, P, Pardali, K. and Moustakas, A. (1999) c-Jun transactivates the promoter of the human p21/WAF-1 gene by acting as a superactivator of the ubiquitous transcription factor Sp1. J. Biol. Chem. 274, 29572-29581

Moustakas, A. and Kardassis, D. (1998) Activation of the human p21/WAF1/Cip1 gene promoter in hepatic cells by interactions between Sp1 and Smad family members. Proc Natl Acad Sci U S A. 95, 6733-8.

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