Tropopoiitiko Fek">TEXAN SA

 Research Team 4:

Title: «Study, prevention and treatment of pathophysiological angiogenesis and inflammation with systems biology approaches»

Supervisor: Eleni Loutrari

 Partners:

 

The research interests of our group focus mainly on the study of angiogenesis and inflammation in the context of pathological conditions (indicative: cancer, cardiovascular and respiratory diseases, diseases related to dysbiosis of the human microbiome) as well as the development of innovative chemopreventive/therapeutic agents.


We are particularly interested in the study of bioactive natural or synthetic compounds and their analogues with potentially improved biological or pharmacokinetic properties as well as in the thorough investigation of their mode of action in target cells and tissues. To this end, we have developed a comprehensive platform for the pre-clinical characterization of test compounds that includes:

 

  • Control of bioactivity at the level of cellular functions and specific biomarkers in cellular models
  • Investigation of involved mechanisms at the level of systemic genomic-proteomic expression and function as well as at the level of intracellular-intercellular signaling networks using bioinformatics analysis
  • Design-optimization of chemopreventive/therapeutic protocols and toxicity assessment of selected (most promising) bioactive compounds in laboratory animals
  • Exploitation of preclinical results in the design of new protocols for clinical assessment and therapeutic treatment (translational research, precision medicine, systems pharmacology-pharmacogenomics)

 

For these purposes, our group utilizes in vitro and in vivo experimental disease models and modern methodologies of cell and molecular biology in combination with high-throughput technologies of systems biology (transcriptomics, functional/signaling proteomics, epigenomics, metabolomics, metagenomics ). By applying specialized tools of computational analysis of –omics data, from our own studies as well as from open access databases, we are able to highlight the "molecular signatures" that are related to the pathological condition under study and/or the response to the examined pharmaceutical agents.


The following research projects are currently in progress:


1. Synthesis and biological evaluation of new generation inhibitors of tyrosine kinase receptors with potentially improved anti-angiogenic activity. Study of structure-activity relationships and investigation of the mechanisms involved using systems biology approaches
2. Study of anti-cancer and/or anti-inflammatory mode of action of natural bioactive compounds by using –omics technologies and bioinformatics data analysis
3. Investigation of the heterogeneity of human hepatocellular carcinoma by computational analysis of multi-omics data of DNA methylation, gene expression and microRNA expression
4. Metagenomics analysis of the microbiome in the blood of patients with schizophrenia and association with inflammatory biomarkers


Collaborations


In addition to work in partnership with the other groups at Thorax Foundation and the A’ Intensive Care Clinic of Evangelismos Hospital, we maintain collaborations with the following institutions and research centers:

 

  • Faculty of Pharmacy NKUA: Laboratory of Pharmaceutical Chemistry and Laboratory of Pharmacognosy and Chemistry of Natural Products
  • School of Medicine NKUA: A' Psychiatric Clinic, Aeginiteio Hospital
  • School of Chemical Engineering NTUA: Laboratory of Biotechnology
  • School of Mechanical Engineering NTUA: Laboratory of Biomedical Systems
  • Biomedical Research Foundation of the Academy of Athens: Center for Systems Biology
  • Center of Excellence "Bioactive Natural Products" NKUA
  • Center of Excellence "Design and Discovery of Drug" NKUA

Funding from GSRT-EU and Public Benefit Institutions (2005-2021)

  • 2014-2021: EPAnEK project 5298 «Synthetic biology: from omics technologies to genomic engineering (OMIC-ENGINE)
  • 2011-2015: National Action, "COOPERATION" Act III "Large Scale Collaborative Projects, project 09 SYN-21-1078: "Development of novel angiogenesis-modulating pharmaceuticals by screening of natural compounds and synthetic analogues"
  • 2014-2015: Public Benefit Foundation I.S. Latsis "Determination of natural inhibitors of human hepatocellular carcinomas through a systems biology approach"
  • 2006-2008: PAVET project 05PAB281 "Development of new enzymatically modified derivatives from compounds of phytochemical origin with improved anti-angiogenic activity"
  • 2005-2008: PENED program project 167: "Development and implementation of biocatalytic processes to upgrade the value of Chios mastic and its components as a dietary supplement in relation to the prevention of pathological angiogenesis"

 

Selected Publications

 

Agioutantis PC, Loutrari H., Kolisis FN. Computational Analysis of Transcriptomic and Proteomic Data for Deciphering Molecular Heterogeneity and Drug Responsiveness in Model Human Hepatocellular Carcinoma Cell Lines Genes 2020, 11, 623 https://doi.org/10.3390/genes11060623


Agioutantis PC, Kotsikoris V, Kolisis FN, Loutrari H. RNA-seq data analysis of stimulated hepatocellular carcinoma cells treated with epigallocatechin gallate and fisetin reveals target genes and action mechanisms. Comput Struct Biotechnol J. 18:686-695. eCollection 2020 https://doi.org/10.1016/j.csbj.2020.03.006


Magkouta, S., Pappas, A.G., Vaitsi, P., Agioutantis, P., Pateras, I.S., Moschos, C., Iliopoulou, M., Kosti, C., Loutrari, H., Gorgoulis, V.G., Kalomenidis, I. Mth-1 favors mesothelioma tumor cell survival and mediates paracrine rescue of bystander endothelium from oxidative damage. JCI Insight 2020, 5(12):e134885 https://doi.org/10.1172/jci.insight.134885.


Michailidou, M., Giannouli, V., Kotsikoris, V., Papadodima, O., Kontogianni, G., Kostakis, I.K., Lougiakis, N., Chatziioannou, A., Kolisis, F.N., Marakos, P., Pouli, N. andLoutrari, H (2016). Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis. European Journal of Medicinal Chemistry, 4: 121:143-57 https://doi.org/10.1016/j.ejmech.2016.05.035


Michailidou, M., Melas, I., Messinis, D., Klamt, S., Alexopoulos, L., Kolisis, F.N. and Loutrari, H. (2015). Network-based analysis of nutraceuticals in human hepatocellular carcinomas reveals mechanisms of chemopreventive action. CPT Pharmacometrics Syst. Pharmacol. 4: 350–361 https://doi.org/10.1002/psp4.40


Valavanis, I., Goudas, T., Michailidou, M., Maglogiannis, I., Loutrari, H. and Chatziioannou, A. (2015). A novel image analysis methodology for the evaluation of angiogenesis in matrigel assays and screening of angiogenesis-modulating compounds in Artificial Intelligence Applications and Innovations Volume 458 of the series IFIP Advances in Information and Communication Technologypp 61-71 https://doi.org/10.1007/978-3-319-23868-5_5


Loutrari, Η., Magkouta, S., Papapetropoulos, A. and Roussos, C. (2011) Mastic Oil Inhibits the Metastatic Phenotype of Mouse Lung Adenocarcinoma Cells. Cancers, 3, 789-801 https://doi.org/10.3390/cancers3010789


Theodossiou, E.,Loutrari, H., Stamatis, H. Roussos C, Kolisis FN. (2011), Biocatalytic synthesis and antitumor activities of novel silybin-acylated derivatives with dicatboxylic acids. N Biotechnol. 28(4):342-8 https://doi.org/10.1016/j.nbt.2011.01.006


Morbidelli, L., Pyriochou, A., Filippi, S., Vassiliades, Y., Roussos, C., Loutrari, H., Giannis, A., Stössel, A., Ziche, M. and Papapetropoulos, A. (2010). The soluble guanylyl cyclase inhibitor NS-2028 reduces vascular endothelial growth factor-induced angiogenesis and permeability. Am J Physiol Regul Integr Comp Physiol., 298(3):R824-32 https://doi.org/10.1152/ajpregu.00222.2009


Xanthakis, E., Theodossiou, E., Magkouta, S., Stamatis, H., Loutrari, H., Roussos, C. and Kolisis, F.N. (2010). Enzymatic transformation of flavonoids and terpenoids: Structural and functional diversity of the novel derivatives. Pure and Applied Chemistry, 82: 1-16 https://doi.org/10.1351/PAC-CON-09-01-19


Moulos, P. Papadodima, O., Chatziioannou, A., Loutrari, H., Roussos C and Kolisis, F.N. (2009). A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival. BMC Med Genomics, 2:68. https://doi.org/10.1186/1755-8794-2-68


Magkouta, S., Stathopoulos, G.T., Psallidas, I., Papapetropoulos, A., Kolisis, F.N., Roussos, C. and Loutrari, H. (2009). Protective effects of mastic oil from Pistacia lentiscus variation chia against experimental growth of Lewis Lung Carcinoma. Nutrition & Cancer, 61(5): 640-648 https://doi.org/10.1080/01635580902825647


Theodossiou, E., Katsoura, M.H., Loutrari, H., Purchartova , K., Kren, V., Kolisis, F.N. and Stamatis, H. (2009). Enzymatic preparation of acylated derivatives of silybin in organic and ionic liquids media and evaluation of their anti-tumor proliferative activity. Biocatalysis and Biotransformations, 27: 161 – 169 http://dx.doi.org/10.1080/10242420902937777


Xanthakis, E.,Magkouta, S., Loutrari, H., Stamatis, H., Roussos, C. and Kolisis, F.N. (2009). Enzymatic synthesis of perillyl alcohol derivatives and investigation of their
anti-proliferative activity. Biocatalysis and Biotransformation, 27: 170– 178 http://dx.doi.org/10.1080/10242420902811089


Xanthakis, E.,Mistriotis, P., Stamatis, H., Magkouta, S., Loutrari, H., Roussos, C. and Kolisis, F.N. (2008). Biotransformations of natural compounds: Structural and functional diversity of novel derivatives. J. Biotechnology, 136, Supplement S280 http://dx.doi.org/10.1016/j.jbiotec.2008.07.600


Stathopoulos, G.T., Moschos, C., Loutrari, H., Kollintza, A., Psallidas, I., Karabela, S., Magkouta, S., Zhou, Z., Papiris, S.A., Roussos, C. and Kalomenidis, I. (2008). Zoledronic acid is effective against experimental malignant pleural effusion. American Journal of Respiratory and Critical Care Medicine, 178:50-59 https://doi.org/10.1164/rccm.200710-1513OC


Loutrari, Η., Magkouta, S., Pyriochou, A., Koika, V., Kolisis, F.N., Papapetropoulos, A. and Roussos, C. (2006). Mastic oil from Pistacia lentiscus var. chia inhibits growth and survival of human K562 leukemia cells and attenuates angiogenesis. Nutrition & Cancer. 55:86-93 https://doi.org/10.1207/s15327914nc5501_11


Mellou, F., Loutrari, H., Stamatis, H., Roussos, C. and Kolisis F.N. (2006). Enzymatic esterification of flavonoids with unsaturated fatty acids: Effect of the novel esters on Vascular Endothelial Growth Factor release from K562 cells. Process Biochemistry. 41:2029-2034 http://dx.doi.org/10.1016/j.procbio.2006.05.002


Kotanidou A., Loutrari H., Papadomichelakis E., Glynos K., Magkou C., Armaganidis A., Papapetropoulos A., Roussos C. and Orfanos S.E. (2006). Inhaled activated protein C attenuates lung injury induced by endotoxin in mice. Vascular Pharmacology, 45: 134-140 https://doi.org/10.1016/j.vph.2006.06.016


Loutrari, H., Hatziapostolou, M., Skouridou, V., Papadimitriou, E., Roussos, C., Kolisis, F.N. and Papapetropoulos, A. (2004) Perillyl alcohol is an angiogenesis inhibitor. J Pharmacol Exp Ther. 311:568-75 https://doi.org/10.1124/jpet.104.070516