Browsing by Author "Durasi, Ilknur Melis"
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Item CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes(PUBLIC LIBRARY SCIENCE, 2015-01-01) Avsar, Timucin; Durasi, Ilknur Melis; Uygunoglu, Ugur; Tutuncu, Melih; Demirci, Nuri Onat; Saip, Sabahattin; Sezerman, O. Ugur; Siva, Aksel; Turanli, Eda TahirMultiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10(-5)) which is important in the immune cell migration, renin-angiotensin (p=6.88x10(-5)) system that induces Th17 dependent immunity, notch signaling (p=1.83x10(-10)) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10(-5)). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.Item In silico analyses and global transcriptional profiling reveal novel putative targets for Pea3 transcription factor related to its function in neurons(PUBLIC LIBRARY SCIENCE, 2017-01-01) Kandemir, Basak; Dag, Ugur; Gungor, Burcu Bakir; Durasi, Ilknur Melis; Erdogan, Burcu; Sahin, Eray; Sezerman, Ugur; Kurnaz, Isil AksanPea3 transcription factor belongs to the PEA3 subfamily within the ETS domain transcription factor superfamily, and has been largely studied in relation to its role in breast cancer metastasis. Nonetheless, Pea3 plays a role not only in breast tumor, but also in other tissues with branching morphogenesis, including kidneys, blood vasculature, bronchi and the developing nervous system. Identification of Pea3 target promoters in these systems are important for a thorough understanding of how Pea3 functions. Present study particularly focuses on the identification of novel neuronal targets of Pea3 in a combinatorial approach, through curation, computational analysis and microarray studies in a neuronal model system, SH-SY5Y neuroblastoma cells. We not only show that quite a number of genes in cancer, immune system and cell cycle pathways, among many others, are either up- or down-regulated by Pea3, but also identify novel targets including ephrins and ephrin receptors, semaphorins, cell adhesion molecules, as well as metalloproteases such as kallikreins, to be among potential target promoters in neuronal systems. Our overall results indicate that rather than early stages of neurite extension and axonal guidance, Pea3 is more involved in target identification and synaptic maturation.