Papers by Olga Papadodima
Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding prote... more Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components of immunoselected hnRNP complexes and having a major nuclear localization. Specifically, we present here the application of the RNA-immunoprecipitation (RIP)-Chip technology to identify a population of nuclear transcripts associated with hnRNP A1-RNPs as isolated from the nuclear extract of either HuR WT or HuR-depleted (KO) mouse embryonic fibroblast (MEF) cells. The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced) with the nuclear hnRNP A1-RNP complexes. Real time PCR analysis was applied to validate a selected number of nuclear mRNA transcripts, as well as to identify pre-spliced transcripts (in addition to their mature mRNA counterpart) within the isolated nuclear hnRNP A1-RNPs. The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle) indicating their concerted function in mRNA metabolism.
Advances in Bioinformatics, 2012
Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throu... more Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throughout its manifestation. The present study aims to exploit bioinformatic tools in order to analyze microarray data of atherosclerotic aortic lesions of ApoE knockout mice, a model widely used in atherosclerosis research. In particular, a dynamic analysis was performed among young and aged animals, resulting in a list of 852 significantly altered genes. Pathway analysis indicated alterations in critical cellular processes related to cell communication and signal transduction, immune response, lipid transport, and metabolism. Cluster analysis partitioned the significantly differentiated genes in three major clusters of similar expression profile. Promoter analysis applied to functional related groups of the same cluster revealed shared putative cis-elements potentially contributing to a common regulatory mechanism. Finally, by reverse engineering the functional relevance of differentially expressed genes with specific cellular pathways, putative genes acting as hubs, were identified, linking functionally disparate cellular processes in the context of traditional molecular description.
Oncotarget, Jan 15, 2014
Kallikrein-related peptidase 5 (KLK5) displays aberrant expression in cancer. However, any functi... more Kallikrein-related peptidase 5 (KLK5) displays aberrant expression in cancer. However, any functional association is missing. Here, we show that reconstitution of KLK5 expression in non-expressing MDA-MB-231 breast cancer cells suppresses malignancy in vitro and in vivo dose-dependently. Reactivation of KLK5 suppressed key EMT genes. Unexpectedly, we identified altered expression of genes encoding enzymes of the mevalonate pathway typical of those observed upon cholesterol starvation. Consistently, we found that SREBF1, the master regulator of the mevalonate pathway was induced. KLK5 re-expression leads to reduced cellular cholesterol and fatty acid synthesis and enhanced uptake of LDL-cholesterol. Suppression of the mevalonate pathway in KLK5 transfectants was further shown by reduced synthesis of isoprenoids. Indeed, we found diminished levels of active RhoA, a signaling oncoprotein that requires prenylation for activation. We propose that reduced RhoA activation plays a dominant ...
TheScientificWorldJournal, 2013
Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%-5% of the global popul... more Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%-5% of the global population constitute two severe mental disorders. e catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. e aim of the study was to perform and interpret the results of a comparative genomic pro�ling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression pro�ling data. �e performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the �nal study was performed based on raw data from a gene expression pro�ling dataset in the postmortem superior temporal cortex of schizophrenics. e data were downloaded from NCBI's GEO datasets.
Advances in Bioinformatics, 2012
Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throu... more Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throughout its manifestation. The present study aims to exploit bioinformatic tools in order to analyze microarray data of atherosclerotic aortic lesions of ApoE knockout mice, a model widely used in atherosclerosis research. In particular, a dynamic analysis was performed among young and aged animals, resulting in a list of 852 significantly altered genes. Pathway analysis indicated alterations in critical cellular processes related to cell communication and signal transduction, immune response, lipid transport, and metabolism. Cluster analysis partitioned the significantly differentiated genes in three major clusters of similar expression profile. Promoter analysis applied to functional related groups of the same cluster revealed shared putative cis-elements potentially contributing to a common regulatory mechanism. Finally, by reverse engineering the functional relevance of differentially expressed genes with specific cellular pathways, putative genes acting as hubs, were identified, linking functionally disparate cellular processes in the context of traditional molecular description.
The Scientific World Journal, 2013
Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%-5% of the global popul... more Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%-5% of the global population constitute two severe mental disorders. e catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. e aim of the study was to perform and interpret the results of a comparative genomic pro�ling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression pro�ling data. �e performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the �nal study was performed based on raw data from a gene expression pro�ling dataset in the postmortem superior temporal cortex of schizophrenics. e data were downloaded from NCBI's GEO datasets.
Proceedings of the 16th International Conference on Engineering Applications of Neural Networks (INNS) - EANN '15, 2015
In this work we present a distributed Health Record System Architecture, capable of integrating a... more In this work we present a distributed Health Record System Architecture, capable of integrating and duly accommodating the processing of heterogeneous, multi-layered (omics, histological images and clinical) data concerning the multi-angled description and management of melanoma patients. The proposed solution comprises a novel design of a layered analytical framework as an expansion of current Electronic Health Record (EHR) systems, which may integrate EHR data, high-volume molecular -omic data, imaging data as well as relevant clinical observations. The case study used is in the field of dermatology, where we attempt to combine the multilayered information for the early detection of skin cancer. The specific architecture, aspires to lower the barrier for the introduction of personalized therapeutic approaches, in the 21 st century in the context of precision medicine. The adopted schema, presumes that through the massive integration of multilayered, voluminous data, describing the disease state at various organizational scales and the parallel processing of those streams, either alone or in conjunction with the others, significant advancement and speed up will occur concerning the quality and output of medical diagnostic tasks or patient management overall, thus paving the way for the introduction of personalized approaches in the therapeutic course. The paper describes in detail the technical issues of implementation along with an initial evaluation and discussion.
13th IEEE International Conference on BioInformatics and BioEngineering, 2013
Oncotarget, Jan 15, 2014
Kallikrein-related peptidase 5 (KLK5) displays aberrant expression in cancer. However, any functi... more Kallikrein-related peptidase 5 (KLK5) displays aberrant expression in cancer. However, any functional association is missing. Here, we show that reconstitution of KLK5 expression in non-expressing MDA-MB-231 breast cancer cells suppresses malignancy in vitro and in vivo dose-dependently. Reactivation of KLK5 suppressed key EMT genes. Unexpectedly, we identified altered expression of genes encoding enzymes of the mevalonate pathway typical of those observed upon cholesterol starvation. Consistently, we found that SREBF1, the master regulator of the mevalonate pathway was induced. KLK5 re-expression leads to reduced cellular cholesterol and fatty acid synthesis and enhanced uptake of LDL-cholesterol. Suppression of the mevalonate pathway in KLK5 transfectants was further shown by reduced synthesis of isoprenoids. Indeed, we found diminished levels of active RhoA, a signaling oncoprotein that requires prenylation for activation. We propose that reduced RhoA activation plays a dominant ...
Proceedings of the IEEE/EMBS Region 8 International Conference on Information Technology Applications in Biomedicine, ITAB, 2010
Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throu... more Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throughout its manifestation. The present study represents an integrative effort, coupling the results of a bioinformatic analysis based on microarray data of atherosclerotic aortic lesions of apoE knockout mice, a model widely used in atherosclerosis research, together with gene expression measurements of human atherosclerotic lesions. A dynamic
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2012
Advances in Bioinformatics, 2012
Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throu... more Atherosclerosis is a multifactorial disease involving a lot of genes and proteins recruited throughout its manifestation. The present study aims to exploit bioinformatic tools in order to analyze microarray data of atherosclerotic aortic lesions of ApoE knockout mice, a model widely used in atherosclerosis research. In particular, a dynamic analysis was performed among young and aged animals, resulting in a list of 852 significantly altered genes. Pathway analysis indicated alterations in critical cellular processes related to cell communication and signal transduction, immune response, lipid transport, and metabolism. Cluster analysis partitioned the significantly differentiated genes in three major clusters of similar expression profile. Promoter analysis applied to functional related groups of the same cluster revealed shared putative cis-elements potentially contributing to a common regulatory mechanism. Finally, by reverse engineering the functional relevance of differentially expressed genes with specific cellular pathways, putative genes acting as hubs, were identified, linking functionally disparate cellular processes in the context of traditional molecular description.
The Scientific World Journal, 2013
Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%-5% of the global popul... more Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%-5% of the global population constitute two severe mental disorders. e catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. e aim of the study was to perform and interpret the results of a comparative genomic pro�ling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression pro�ling data. �e performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the �nal study was performed based on raw data from a gene expression pro�ling dataset in the postmortem superior temporal cortex of schizophrenics. e data were downloaded from NCBI's GEO datasets.
International Journal of Molecular Sciences, 2013
Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding prote... more Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components of immunoselected hnRNP complexes and having a major nuclear localization. Specifically, we present here the application of the RNA-immunoprecipitation (RIP)-Chip technology to identify a population of nuclear transcripts associated with hnRNP A1-RNPs as isolated from the nuclear extract of either HuR WT or HuR-depleted (KO) mouse embryonic fibroblast (MEF) cells. The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced) with the nuclear hnRNP A1-RNP complexes. Real time PCR analysis was applied to validate a selected number of nuclear mRNA transcripts, as well as to identify pre-spliced transcripts (in addition to their mature mRNA counterpart) within the isolated nuclear hnRNP A1-RNPs. The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle) indicating their concerted function in mRNA metabolism.
Journal of Neurochemistry, 2005
BM88 is a neurone-specific protein implicated in cell cycle exit and differentiation of neuronal ... more BM88 is a neurone-specific protein implicated in cell cycle exit and differentiation of neuronal precursors. It is widely expressed in terminally differentiated neurones but also in neuronal progenitors, albeit in lower levels. Thus BM88 expression shows a tight correlation with the progression of progenitor cells towards neuronal differentiation. Here we report the genomic organization and proximal promoter characterization of the human and mouse BM88 genes. Both promoters lie in a CpG island, are TATA-less and have multiple transcription start sites. Deletion analysis performed on the human BM88 gene revealed an 88 bp minimal promoter fragment that is preferentially active in neural cells. Importantly, this minimal promoter is sufficient to confer specific transcriptional activity in primary neurones, but not in glial cells. Within the promoter region there are four functional Sp1-binding sites. Simultaneous mutations to all four Sp1 sites results in complete loss of promoter activity. Transactivation experiments revealed that Sp1 directly activates the BM88 promoter while activation also occurs in the presence of neurogenin-1. Characterization of the promoter elements that control neurone-specific and developmental expression of BM88 should contribute to the elucidation of the transcriptional networks that regulate the transition from a proliferative neural progenitor to a postmitotic neurone.
FEBS Letters, 2008
Histone deacetylase inhibitors arrest the growth of neuroblastoma cells and induce differentiatio... more Histone deacetylase inhibitors arrest the growth of neuroblastoma cells and induce differentiation. Identification of target genes that co-ordinate and mediate these effects is important for understanding the function of this novel class of antitumour drugs. We report here that trichostatin-A (TSA) specifically induces the transcription of Cend1, a neuronal-lineage specific regulator of cell cycle exit and differentiation, in neuroblastoma Neuro2A cells, but not in non-neuronal cells. Furthermore, we show that knockdown of Cend1 alleviates both the anti-proliferative and differentiation effect of TSA. Our findings suggest that Cend1 is an important molecular target for HDAC inhibition.
BMC Medical Genomics, 2009
Background: Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with... more Background: Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level.
13th IEEE International Conference on BioInformatics and BioEngineering, 2013
The scope of this study is the identification of gender-independent muscle transcriptional differ... more The scope of this study is the identification of gender-independent muscle transcriptional differences between younger and older subjects using skeletal muscle gene expression profiles. Towards this end, a combination of statistical methods, functional analyses, and machine learning techniques were exploited, and applied on an integrative dataset of publicly available microarray data obtained from healthy males and females. Through the proposed framework, a set of 46 reliable genes was identified that comprise a candidate gender-independent aging signature in human skeletal muscle. The identification was based on differential expression, information gain content, and significance regarding their central regulatory role in the underlying active molecular networks in the GO. The resulted gene subset was also tested for its generalization potency regarding the classification task, through the use of a series of classifiers, and results show that high classification accuracies could be obtained. Therefore, the selected genes comprise a promising group of biomarkers of ageing in human skeletal muscle to be evaluated in future studies.
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Papers by Olga Papadodima