Researcher: Mortazavi, Deniz
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Mortazavi, Deniz
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Publication Open Access Comparative transcriptomic analyses of peripheral blood mononuclear cells of Covid-19 patients without pneumonia and with severe pneumonia in the first year of follow-up(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Cetinkaya, Pelin Duru; Eldem, Vaha; Argun Baris, Serap; Kokturk, Nurda; Kuralay, Selim Can; Pinar Deniz, Pelin; Baydar Toprak, Oya; Yildiz Gulhan, Pinar; Sagcan, Gulseren; Kose, Neslihan; Tomruk Erdem, Aysegul; Fakili, Fusun; Ozturk, Onder; Basyigit, Ilknur; Boyaci, Hasim; Azak, Emel; Ulukavak Ciftci, Tansu; Oguzulgen, Ipek Kivilcim; Ozger, Hasan Selcuk; Aysert Yildiz, Pinar; Hanta, Ismail; Ataoglu, Ozlem; Ercelik, Merve; Cuhadaroglu, Caglar; Okur, Hacer Kuzu; Tor, Muge Meltem; Nurlu Temel, Esra; Kul, Seval; Itil, Oya; N/A; Kayalar, Özgecan; Rajabi, Hadi; Konyalılar, Nur; Mortazavi, Deniz; Korkunç, Seval Kübra; Erkan, Sinem; Aksoy, Gizem Tuşe; Eyikudamacı, Gül; Tütüncü, Yıldız; Bayram, Hasan; Koç University Research Center for Translational Medicine (KUTTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of MedicineThe multisystemic effects of COVID-19 may continue for a longer time period following the acute phase, depending on the severity of the disease. However, long-term systemic transcriptomic changes associated with COVID-19 disease and the impact of disease severity are not fully understood. We aimed to investigate the impact of COVID-19 and its severity on transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) following 1 year of the disease. PBMCs were isolated from the peripheral blood of healthy control donors who did not have COVID-19 (C; n = 13), from COVID-19 patients without pneumonia (NP; n = 11), and from COVID-19 patients with severe pneumonia (SP; n = 10) after 1-year of follow-up. Following RNA isolation from PBMCs, high-quality RNAs were sequenced after creating a library. Differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified using Benjamini–Hochberg correction and they were analysed for hierarchical clustering and principal component analysis (PCA). Intergroup comparisons (C vs. NP, C vs. SP, and NP vs. SP) of DEGs and DElncRNAs were performed and hub genes were determined. Functional enrichment analyses of DEGs and DElncRNAs were made using Metascape (v3.5.20240101) and the first version of NCPATH. The RNA sequencing analysis revealed 4843 DEGs and 1056 DElncRNAs in “C vs. NP”, 1651 DEGs and 577 DElncRNAs in “C vs. SP”, and 954 DEGs and 148 DElncRNAs in “NP vs. SP”, with 291 DEGs and 70 DElncRNAs shared across all groups, respectively. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation and downregulated DEGs to viral infections and immune responses. The analysis showed that 291 common and 14 hub genes were associated with pneumonia and that these genes could be regulated by the transcription factors JUN and NFκB1 carrying the NFκB binding site. We also revealed unique immune cell signatures across DEG categories indicating that the upregulated DEGs were associated with neutrophils and monocytes, while downregulated DEGs were associated with CD4 memory effector T cells. The comparative transcriptomic analysis of NP and SP groups with 52 gene signatures suggestive of IPF risk showed a lower risk of IPF in the SP group than the NP patients. Our findings suggest that COVID-19 may cause long term pathologies by modulating the expression of various DEGs, DeLncRNAs, and hub genes at the cellular level. © 2024 by the authors.Publication Metadata only Issue 4—impact of air pollution on Covid-19 mortality and morbidity: an epidemiological and mechanistic review(Elsevier Espana S.L.U, 2024) Elçi, Müge Akpınar; Taborda-Barata, Luis; Viegi, Giovanni; Bayram, Hasan; Konyalılar, Nur; Rajabi, Hadi; Mortazavi, Deniz; Kayalar, Özgecan; Dikensoy, Öner; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; Koç University HospitalAir pollution is a major global environment and health concern. Recent studies have suggested an association between air pollution and COVID-19 mortality and morbidity. In this context, a close association between increased levels of air pollutants such as particulate matter ≤2.5 to 10 µM, ozone and nitrogen dioxide and SARS-CoV-2 infection, hospital admissions and mortality due to COVID 19 has been reported. Air pollutants can make individuals more susceptible to SARS-CoV-2 infection by inducing the expression of proteins such as angiotensin converting enzyme (ACE)2 and transmembrane protease, serine 2 (TMPRSS2) that are required for viral entry into the host cell, while causing impairment in the host defence system by damaging the epithelial barrier, muco-ciliary clearance, inhibiting the antiviral response and causing immune dysregulation. The aim of this review is to report the epidemiological evidence on impact of air pollutants on COVID 19 in an up-to-date manner, as well as to provide insights on in vivo and in vitro mechanisms. © 2024 Sociedade Portuguesa de PneumologiaPublication Metadata only Omics in precision medicine(Springer Nature, 2023) ; Kayalar, Özgecan; Rajabi, Hadi; Mortazavi, Deniz; Bayram, Hasan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine;Cancer is a multifaceted and complex disease that results from the disruption of genetic, epigenetic, and metabolic systems responsible for maintaining physiological conditions in the cell. Despite an increase in studies on the pathogenesis of cancer and numerous advancements in diagnosis and treatment in recent years, drug treatments that are expected to be beneficial due to the heterogeneous nature of cancer are not effective in every patient. In some cases, cancer may become aggressive due to drug resistance in the tumour cell or recurrence after treatment. The development of personalized medicine approaches, which are crucial for a comprehensive understanding of the nature of the tumour in each patient, has emerged in the last 10-15 years as a result of this challenging situation. Establishing therapy options and managing treatments in the context of data from multi-omic approaches is believed to be urgently necessary, and this view has also accelerated the implementation of precision medicine in oncology in recent years. The top five most prevalent cancers in the world will be the subject of this chapter as we review fundamental ideas and current technologies in genomics, epigenomics, transcriptomics, proteomics and phosphoproteomics, metabolomics, and single-cell omics research. We also discuss their potential for use in diagnosis and therapy in precision medicine in oncology by summarizing potential molecular targets and molecules discovered in multi-omics techniques. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.Publication Metadata only Impact of particulate air pollution on airway injury and epithelial plasticity;underlying mechanisms(Frontiers Media Sa, 2024) Wang, Jun; Kayalar, Özgecan; Rajabi, Hadi; Konyalılar, Nur; Mortazavi, Deniz; Aksoy, Gizem Tuşe; Bayram, Hasan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of MedicineAir pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction of air pollutants, and studies have demonstrated that it can cause airway inflammation and injury. The airway epithelium forms the first barrier of defense against inhaled toxicants, such as PM. Airway epithelial cells clear airways from inhaled irritants and orchestrate the inflammatory response of airways to these irritants by secreting various lipid mediators, growth factors, chemokines, and cytokines. Studies suggest that PM plays an important role in the pathogenesis of chronic airway diseases by impairing mucociliary function, deteriorating epithelial barrier integrity, and inducing the production of inflammatory mediators while modulating the proliferation and death of airway epithelial cells. Furthermore, PM can modulate epithelial plasticity and airway remodeling, which play central roles in asthma and COPD. This review focuses on the effects of PM on airway injury and epithelial plasticity, and the underlying mechanisms involving mucociliary activity, epithelial barrier function, airway inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial transition, and airway remodeling.Publication Metadata only The role of reactive nitrogen species as biomarkers of disease severity in COVID-19(European Respiratory Society (ERS), 2022) Akyil, F. Tokgoz; Altin, S.; N/A; N/A; N/A; N/A; Department of Molecular Biology and Genetics; N/A; N/A; Department of Molecular Biology and Genetics; Konyalılar, Nur; Kayalar, Özgecan; Mortazavi, Deniz; Rajabi, Hadi; Korkunç, Seval Kübra; Erkan, Selim; Gönenli, Mehmet Gökhan; Bayram, Hasan; PhD Student; Researcher; PhD Student; PhD Student; Master Student; Other; Other; Teaching Faculty; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; N/A; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; N/A; N/A; School of Medicine; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; 350445; 4890N/APublication Metadata only Genetic variability and clinical spectrum of limb-girdle muscular dystrophy in a cohort of Turkish patients(Springernature, 2020) Avcı, Seymen; N/A; N/A; N/A; N/A; N/A; N/A; Mortazavi, Deniz; Vanlı-Yavuz, Ebru Nur; Börklü Yücel, Esra; Eraslan, Serpil; Oflazer, Piraye; Kayserili, Hülya; PhD Student; Doctor; Other; Researcher; Faculty Member; Faculty Member; School of Medicine / Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine / Koç University HospitGraduate School of Health Sciences; N/A; School of Medicine; School of Medicine; N/A; 251177; N/A; N/A; N/A; 7945N/APublication Open Access Emerging role of exosomes in the pathology of chronic obstructive pulmonary diseases; destructive and therapeutic properties(BioMed Central, 2022) Rahbarghazi, Reza; Rajabi, Hadi; Konyalılar, Nur; Erkan, Sinem; Mortazavi, Deniz; Korkunç, Seval Kübra; Kayalar, Özgecan; Bayram, Hasan; PhD Student; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; 4890Chronic obstructive pulmonary disease (COPD) is known as the third leading cause of human death globally. Enhanced chronic inflammation and pathological remodeling are the main consequences of COPD, leading to decreased life span. Histological and molecular investigations revealed that prominent immune cell infiltration and release of several cytokines contribute to progressive chronic remodeling. Recent investigations have revealed that exosomes belonging to extracellular vesicles are involved in the pathogenesis of COPD. It has been elucidated that exosomes secreted from immune cells are eligible to carry numerous pro-inflammatory factors exacerbating the pathological conditions. Here, in this review article, we have summarized various and reliable information about the negative role of immune cell-derived exosomes in the remodeling of pulmonary tissue and airways destruction in COPD patients.Publication Open Access Epi-miRNAs: regulators of the histone modification machinery in human cancer(Hindawi, 2022) Sohrabi, B.; Mosallaei, M.; Nariman Saleh Fam, Z.; Bastami, M.; Mansoori, Y.; Daraei, A.; Zununi Vahed, S.; Navid, S.; Saadatian, Z.; Jamialahmadi, T.; Teng, Y.; Sahebkar A.; Mortazavi, Deniz; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)Cancer is a leading cause of death and disability worldwide. Epigenetic deregulation is one of the most critical mechanisms in carcinogenesis and can be classified into effects on DNA methylation and histone modification. MicroRNAs are small noncoding RNAs involved in fine-tuning their target genes after transcription. Various microRNAs control the expression of histone modifiers and are involved in a variety of cancers. Therefore, overexpression or downregulation of microRNAs can alter cell fate and cause malignancies. In this review, we discuss the role of microRNAs in regulating the histone modification machinery in various cancers, with a focus on the histone-modifying enzymes such as acetylases, deacetylases, methyltransferases, demethylases, kinases, phosphatases, desumoylases, ubiquitinases, and deubiquitinases. Understanding of microRNA-related aberrations underlying histone modifiers in pathogenesis of different cancers can help identify novel therapeutic targets or early detection approaches that allow better management of patients or monitoring of treatment response.