Investigation of the role of the «Environment» in the etiology of disease and morbidity in humans.

The emerging concept of the "exposome" refers to the totality of the exposures suffered by an individual, coming from all sources, including the environment, food, and psycho-social components, from conception onwards. One of the key tools for developing and applying the exposome concept is the use of global sets of biomarkers (-omics) as generic measures of the internal exposome and disease risk. We focus on exploring the role of exposure to toxic environmental agents as a modulator of the epigenetic mechanisms of control of gene expression and hence of adverse health outcomes such as cancer and neurodevelopmental disorders. Cohort-based field studies and in vitro and in vivo studies are being implemented.

Selected Publications

• Vidali, M.-S., Dailianis, S., Vlastos, D., Georgiadis, P., PCB cause global DNA hypomethylation of human peripheral blood monocytes in vitro. Environ. Toxicol. Pharmacol., 2021,  87, 103696.
  https://doi.org/10.1016/j.etap.2021.103696
• Georgiadis, P., Gavriil, M., Rantakokko, P., Ladoukakis, E., Botsivali, M., Kelly, R.S., Bergdahl, I.A., Kiviranta, H., Vermeulen, R.C.H., Spaeth, F., Hebbels, D.G.A.J., Kleinjans, J.C.S., de Kok, T.M.C.M., Palli, D., Vineis, P., Kyrtopoulos, S.A., DNA methylation profiling implicates exposure to PCBs in the pathogenesis of B-cell chronic lymphocytic leukemia. Environment international, 2019, 126, 24–36.
  https://doi.org/10.1016/j.envint.2019.01.068
• Ek, W.E., Tobi, E.W., Ahsan, M., Lampa, E., Ponzi, E., Kyrtopoulos, S.A., Georgiadis, P., Lumey, L.H., Heijmans, B.T., Botsivali, M., Bergdahl, I.A., Karlsson, T., Rask-Andersen, M., Palli, D., Ingelsson, E., Hedman, A.K., Nilsson, L.M., Vineis, P., Lind, L., Flanagan, J.M., Johansson, A., Tea and coffee consumption in relation to DNA methylation in four European cohorts. Human Molecular Genetics, 2017, 26, 3221–3231.
  https://doi.org/10.1093/hmg/ddx194
• Georgiadis, P., Liampa, I., Hebels, D.G., Krauskopf, J., Chatziioannou, A., Valavanis, I., de Kok, T.M.C.M., Kleinjans, J.C.S., Bergdahl, I.A., Melin, B., Spaeth, F., Palli, D., Vermeulen, R.C.H., Vlaanderen, J., Chadeau-Hyam, M., Vineis, P., Kyrtopoulos, S.A., Gottschalk, R., van Leeuwen, D., Timmermans, L., Botsivali, M., Bendinelli, B., Kelly, R., Portengen, L., Saberi-Hosnijeh, F., Hallmans, G., Lenner, P., Keun, H.C., Siskos, A., Athersuch, T.J., Kogevinas, M., Stephanou, E.G., Myridakis, A., Fazzo, L., Santis, M.D., Comba, P., Kiviranta, H., Rantakokko, P., Airaksinen, R., Ruokojärvi, P., Gilthorpe, M., Fleming, S., Fleming, T., Tu, Y.-K., Jonsson, B., Lundh, T., Chen, W.J., Lee, W.-C., Hsiao, C.K., Chien, K.-L., Kuo, P.-H., Hung, H., Liao, S.-F., Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis. BMC Genomics, 2017, 18.
  https://doi.org/10.1186/s12864-017-4117-4
• Georgiadis, P., Hebels, D.G., Valavanis, I., Liampa, I., Bergdahl, I.A., Johansson, A., Palli, D., Chadeau-Hyam, M., Chatziioannou, A., Jennen, D.G.J., Krauskopf, J., Jetten, M.J., Kleinjans, J.C.S., Vineis, P., Kyrtopoulos, S.A., Gottschalk, R., van Leeuwen, D., Timmermans, L., de Kok, T.M.C.M., Botsivali, M., Bendinelli, B., Kelly, R., Vermeulen, R., Portengen, L., Saberi-Hosnijeh, F., Melin, B., Hallmans, G., Lenner, P., Keun, H.C., Siskos, A., Athersuch, T.J., Kogevinas, M., Stephanou, E.G., Myridakis, A., Fazzo, L., De Santis, M., Comba, P., Kiviranta, H., Rantakokko, P., Airaksinen, R., Ruokojärvi, P., Gilthorpe, M., Fleming, S., Fleming, T., Tu, Y.-K., Jonsson, B., Lundh, T., Chen, W.J., Lee, W.-C., Kate Hsiao, C., Chien, K.-L., Kuo, P.-H., Hung, H., Liao, S.-F., Omics for prediction of environmental health effects: Blood leukocyte-based cross-omic profiling reliably predicts diseases associated with tobacco smoking. Scientific Reports, 2016, 6, 20544.
  https://doi.org/10.1038/srep20544

Investigation of the role of gut microbiome in wellbeing as well as in the etiology of disease and morbidity in humans

The study of the biological effects of neutraceuticals at cellular level provides the molecular basis for their anti-tumor function and helps to establish the platform for generating more potent chemopreventive and even chemotherapeutic agents. We aim to unravel the role of neutraceuticals in cancer prevention and well-being to develop novel functional products of high added value through exploiting the Greek biodiversity. Supported by and building on the FUNglucan project (2018-2021) and through applying holistic approaches such as NMR Metabolomics and 16S Next-Generation Sequencing (NGS) metagenomics, we aim at identifying dietary factors with enhanced prebiotic activity given the development of novel food products which promote health and quality of life, of the elderly in particular. In vitro, in vivo, ex vivo, as well as clinical intervention studies, are being implemented
Holistic approaches (Metabolomics and 16S NGS metagenomics are also implemented in two other National or private sector funded projects:

• Osteome (2019-2023): aiming at the design and development of dietary supplements for osteoporosis through mechanisms affecting the gut microbiome-study of effectiveness and tolerability in the innovative dietary supplement and
• Rontis B: comparison of the 16S NGS Metagenomic and Metabolomic profile of newborns fed exclusively with breast milk compared to infant formula-fed newborns

Selected Publications

• Vlassopoulou, M., Paschalidis, N., Savvides, A.L., Saxami, G., Mitsou, E.K., Kerezoudi, E.N., Koutrotsios, G., Zervakis, G.I., Georgiadis, P., Kyriacou, A., Pletsa, V. Immunomodulating Activity of Pleurotus eryngii Mushrooms Following Their In Vitro Fermentation by Human Fecal Microbiota. J Fungi (Basel). 2022 , 8.  
  https://doi:10.3390/jof804032
• Boulaka, A., Christodoulou, P., Vlassopoulou, M., Koutrotsios, G., Bekiaris, G., Zervakis, G.I., Mitsou, E.K., Saxami, G., Kyriacou, A., Zervou, M., Georgiadis, P., Pletsa, V.,(2020). Genoprotective Properties and Metabolites of β-Glucan-Rich Edible Mushrooms  Following Their In Vitro Fermentation by Human Faecal Microbiota. Molecules 25.
  https://doi.org/10.3390/molecules25153554
• Turunen, K.T., Pletsa, V., Georgiadis, P., Triantafillidis, J.K., Karamanolis, D., Kyriacou, A., Impact of beta-glucan on the Fecal Water Genotoxicity of Polypectomized Patients. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2016, 68, 560–567. https://doi.org/10.1080/01635581.2016.1156713

Investigation of the molecular mechanisms of genotoxicity, carcinogenesis and cell death

In the context of drug design and discovery, the development of bioactive compounds against selected therapeutic targets and their evaluation in relevant preclinical disease models/intervention studies is of utmost importance for chemoprevention and treatment.
The Comet Assay has been widely used for detecting primary DNA damage in individual cells. The micronucleus (MN) test is also a well-established assay for detecting clastogenicity and aneugenicity. We utilize these two assays to assess the genotoxicity or anti-genotoxicity of novel bioactive synthetic or natural compounds or mixtures.
On the other hand, chemotherapeutic agents inducing DNA damage may activate cell death by apoptosis or necrosis. The molecular basis underlying the decision- making process is currently the subject of intense investigation because a deeper understanding of how a given chemotherapy affects all of the signaling pathways involved in cell death is highly relevant in order to develop more effective therapeutics and prevent recurrence. We assess geno/cytotoxicity of novel bioactive lead compounds and further study the molecular mechanism underlying their action in view of their use as chemotherapeutic drugs.We emphasize on the identification/validation of new prognostic chemo-sensitivity/resistance biomarkers, related to cell death pathways and the cell's response to DNA damaging insults.

Selected Publications

• Boulaka, A., Christodoulou, P., Vlassopoulou, M., Koutrotsios, G., Bekiaris, G., Zervakis, G.I., Mitsou, E.K., Saxami, G., Kyriacou, A., Zervou, M., Georgiadis, P., Pletsa, V.,(2020)
  Genoprotective Properties and Metabolites of β-Glucan-Rich Edible Mushrooms  Following Their In Vitro Fermentation by Human Faecal Microbiota. Molecules 25. https://doi.org/10.3390/molecules25153554

The rise of interest in epigenetic mechanisms has allowed the identification of a new type of biomarker, DNA methylation, which is of great potential for many applications. In some cases, DNA methylation based biomarkers have proven to be more specific and sensitive than commonly used protein biomarkers, which could clearly justify their use in clinical practice and research. We utilize genome-wide screening methods (Illumina InfiniummethylationEPICbeadchip) and locus- or gene-specific analysis (pyrosequencing) in different types of samples such as tissues and FFPE samples, as well as liquid biopsies.

• Hatzioannou, A., Banos, A., Sakelaropoulos, T., Fedonidis, C., Vidali, M.-S., Kohne, M., Handler, K., Boon, L., Henriques, A., Koliaraki, V., Georgiadis, P., Zoidakis, J., Termentzi, A., Beyer, M., Chavakis, T., Boumpas, D., Tsirigos, A., Verginis, P., An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion. Nature immunology, 2020, 21, 75–85.
  https://doi.org/10.1038/s41590-019-0555-2

The members of the team participate in the administration/organization  and teaching  in the interdepartmental, interdisciplinarypostgraduate programmes "Oncology: from Oncogenesis to Therapy", (Joint Master's Degree, University of Crete/National Hellenic Research Foundation) and "Bioenterpreneurship" http://bioepixirin.bio.uth.gr/, (joint Master's Degree, University of Thessaly/National Hellenic Research Foundation.

The members of the team actively and regularly participate in

• the organization of the "Science & Society" annual event of the National Hellenic Research Foundation aiming at communicating front line scientific issues to the general public: "Translational research: the coalescence of Biology and Medicine for the effective treatment of multifactorial diseases", March 2015 / "Safe and health promoting food, truths and lies", March 2016 / "Diet in the Mediterranean: Historical Aspects and Biochemical Approaches", March 2017 / "Youth, Antiaging and Longevity: Modern Approaches to Biological Age through the Historical and Biological Sciences", March 2018
• the Researcher's Night and Athens Science Festival events
• Science Communication & Dissemination Events