Yandım, Cihangir

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https://hdl.handle.net/20.500.14365/7118
Name Variants
Yandim, Ci̇hangi̇r
Yandim, C.
Yandim, Cihangir
Yandım, Ci̇hangi̇r
Yandım, C.
Job Title
Email Address
cihangir.yandim@ieu.edu.tr
Main Affiliation
05.08. Genetics and Bioengineering
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Current Staff
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0000-0002-2050-6186
Scopus Author ID
36474168400
Turkish CoHE Profile ID
394B75BF1833E66F
Google Scholar ID
MYlNBPoAAAAJ
WoS Researcher ID
AAA-2250-2021
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Cihangir_Yandim.jpg (10.08 KB)

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Documents

21

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502

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Documents

22

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482

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Scholarly Output

24

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16

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7

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WoS Citation Count

119

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122

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6

WoS Citations per Publication

4.96

Scopus Citations per Publication

5.08

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11

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7

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Journal of Biosciences2
Turkısh Journal of Bıology2
Computatıonal Bıology And Chemıstry1
Gene1
International Journal of Biological Macromolecules1
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Now showing 1 - 10 of 24
  • Thumbnail Image
    Article
    Citation - WoS: 3
    Citation - Scopus: 3
    Identification of Ppa1 Inhibitor Candidates for Potential Repurposing in Cancer Medicine
    (Wiley, 2023-09-21) Menteş, Muratcan; Yandım, Cihangir
    Inorganic pyrophosphatase 1 (PPA1) is pivotal to cellular metabolism as it facilitates the hydrolysis of PPi-a by-product of various metabolic processes that influence cell growth and differentiation. Overexpression of PPA1 enzyme has been linked to diminished patient survival and was shown to influence tumor cell dynamics, thereby positioning it as a potential therapy target for a variety of cancers including colorectal cancer, diffuse large B-cell lymphoma, and lung adenocarcinoma. Despite this therapeutic promise, there are no known inhibitors of PPA1 as of today. In this study, we searched for potential PPA1 inhibitors using a molecular docking screen of 30 470 compounds with a history of clinical trials and/or US Food and Drug Administration approval. We specifically targeted the active pocket that coincides with the established catalytic domain. Our screen identified promising hits, which we further subjected to ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering. Subsequent molecular dynamics (MD) analyses were conducted on devazepide, quinotolast, and tarazepide-the three substances that successfully navigated all filters. MD analyses reinforced the stability of the protein-ligand complexes and confirmed ligand binding, as substantiated by our root mean square deviation, radius of gyration and secondary structures of proteins analyses. Furthermore, Molecular Mechanics Poisson-Boltzmann Surface Area calculations post-MD identified devazepide and quinotolast as showing higher binding affinities; being supported by principal component analysis, free energy landscape, and dynamic cross-correlation matrix results. Overall, our study reveals devazepide and quinotolast as potential candidates for PPA1 inhibition which could be considered for repurposing studies that need further experimental validation. These results not only reveal a potential for clinical repurposing for PPA1 inhibition but they also offer valuable insights into the development of future compounds for targeting the crucial PPA1 enzyme.
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    Article
    Comparisons Between Young, Aged, and Alzheimer's Brains Reveal Specific Expression Patterns for a Subset of Transposons and Satellite Repeats
    (Indian Acad Sciences, 2025-10-25) Turan, Elif; Celtik, Busranur; Daglar, Gokce; Kaya, Ilayda; Tufekci, Mert; Yandim, Cihangir
    Recent studies have highlighted the involvement of repeat-derived transcripts in the pathological transcriptome of Alzheimer's disease (AD). However, it remains unclear whether these transcripts arise as a consequence of aging or are directly associated with AD pathology. Particularly, the specific contribution of satellite repeats to this phenomenon has not been systematically investigated. In this study, we profiled the non-coding expression patterns of all repetitive DNA elements - including satellites - across healthy young, healthy aged, and aged AD brain samples. Comparative transcriptome analysis revealed only a single differentially expressed repeat between aged and young brains. In contrast, AD brains exhibited significant expression changes in eight specific repeat elements relative to their healthy aged counterparts. Among these AD-specific repeats, the satellite repeat HSATII showed the highest fold change and a modest increase in histone acetylation levels, suggesting potential regulatory or feedback mechanisms in AD pathology. Weighted Gene Co-Expression Network Analysis (WGCNA) identified modules of co-expressed genes and repeats, revealing a network moderately correlated with the AD phenotype and indicating complex interactions between repeats and genes during disease onset. Collectively, our comprehensive analysis of repeat expression in post-mortem human AD brains demonstrates alterations in transposon and satellite repeat expression patterns that are distinct from age-related changes
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    Article
    Comparisons Between Young, Aged, and Alzheimer's Brains Reveal Specific Expression Patterns for a Subset of Transposons and Satellite Repeats
    (Indian ACAD Sciences, 2025-10-25) Turan, E.; Çeltik, B.; Dağlar, G.; Kaya, İ.; Tu Fekçi, M.; Yandim, C.; Tufekci, Mert
    Recent studies have highlighted the involvement of repeat-derived transcripts in the pathological transcriptome of Alzheimer's disease (AD). However, it remains unclear whether these transcripts arise as a consequence of aging or are directly associated with AD pathology. Particularly, the specific contribution of satellite repeats to this phenomenon has not been systematically investigated. In this study, we profiled the non-coding expression patterns of all repetitive DNA elements - including satellites - across healthy young, healthy aged, and aged AD brain samples. Comparative transcriptome analysis revealed only a single differentially expressed repeat between aged and young brains. In contrast, AD brains exhibited significant expression changes in eight specific repeat elements relative to their healthy aged counterparts. Among these AD-specific repeats, the satellite repeat HSATII showed the highest fold change and a modest increase in histone acetylation levels, suggesting potential regulatory or feedback mechanisms in AD pathology. Weighted Gene Co-Expression Network Analysis (WGCNA) identified modules of co-expressed genes and repeats, revealing a network moderately correlated with the AD phenotype and indicating complex interactions between repeats and genes during disease onset. Collectively, our comprehensive analysis of repeat expression in post-mortem human AD brains demonstrates alterations in transposon and satellite repeat expression patterns that are distinct from agerelated changes. This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
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    Master Thesis
    Computational Design of Nanobodies Targeting the Neoantigens of Oncogenic Kras G12 Mutations
    (2024) Menteş, Muratcan; Yandım, Cihangir
    Pankreatik duktal adenokarsinom (PDAC), kötü prognozu ve sınırlı tedavi seçenekleri ile en ölümcül kanserlerden biri olmaya devam etmektedir. KRAS mutasyonları, özellikle G12 sıcak nokta kalıntısındaki mutasyonlar, PDAC'deki en yaygın ve en erken gerçekleşen olaylar arasında yer almaktadır. Bu nedenle, KRAS tarafından oluşturulan neoantijenler, antikorlar kullanılarak tanı ve tedavi için potansiyel hedefler olarak önerilmiştir. Ancak, antikorlar büyük makromoleküllerdir ve PDAC'nın yoğun ve nabız atan mikroçevresinin oluşturduğu zorluklarla karşı karşıya kalmaktadırlar. Bu çalışma, antikorların çok daha küçük karşılıkları olan nanobody'lerin hesaplamalı tasarımını amaçlamaktadır. Bu makromoleküller, KRAS G12 neoantijenlerini hedefleme ve daha önce belirtilen zorlukların üstesinden gelme potansiyeline sahip olabilirler. Nanobody'lerin tasarımı için, KRAS neoantijenlerine bağlandığı bilinen T-Hücre Reseptörleri ve antikorlardan alınan tamamlayıcı-belirleyici bölgeler, stabil bir nanobody iskeletine yerleştirildikten sonra, bu belirleyici bölgelerin eklenmesiyle oluşturulan nanobody'lerin 3 boyutlu yapıları oluşturulmuş ve KRAS G12 peptit-HLA (İnsan lökosit antijeni) komplekslerine karşı bağlanma ilişkileri, moleküler docking ve moleküler dinamik simülasyonları kullanılarak değerlendirilmiştir. Peptit-nanokor etkileşim enerjileri, Moleküler Mekanik Poisson-Boltzmann Yüzey Alanı (MM-PBSA) analizleri ile hesaplanmış ve daha ayrıntılı olarak 'decomposition' analizleri ile incelenmiştir. In silico sonuçlarımız, nanobody-9'un KRAS G12D neoantijenine spesifik bağlanma ilişkisi gösterdiğini ve aynı zamanda wildtype KRAS'tan ortaya çıkabilecek olası peptitler için düşük bağlanma ilişkisini koruduğunu ortaya koymuştur. Burada sunulan bulgular, daha ileri in vitro ve in vivo doğrulama deneylerini gerektirmektedir. Gelecekteki araştırmalar, nanobody-9'un tanısal ve terapötik potansiyelini keşfederek, nihai hedef olarak klinik uygulamalara yönelik ilerlemeyi sağlayabilir.
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    Article
    Citation - WoS: 17
    Citation - Scopus: 18
    Dysregulated Expression of Repetitive Dna in Er+/Her2-breast Cancer
    (Elsevier Science Inc, 2019-11) Yandim, Cihangir; Karakulah, Gokhan
    Limited studies on breast cancer indicated pathogenic changes in the expressions of some repeat elements. A global analysis was much needed within this context to distinguish the most significant repeats from more than a thousand repeat motifs. Utilising a previously presented RNA-seq dataset, we studied expression changes of all repeats in ER+/HER2- human breast tumour samples obtained from 22 patients in comparison to matched normal tissues. Fifty six (56) repeat subtypes including satellites and transposons were found to be differentially expressed and most of them were novel for breast cancer. HERVKC4-int and HERV1_LTRc, whose expressions correlated well with that of the estrogen receptor gene ESR1, were upregulated at the highest level. REP522 and D20S16 satellites were also significantly upregulated along with insignificant increases in the expressions of other satellites including HSATI and BSR/beta. Interestingly, expressions of REP522 and D20S16 correlated with many key breast cancer pathway (e.g. BRCA1, BRCA2, AKT1, MTOR, KRAS) and survival genes; possibly highlighting their importance in the carcinogenesis of breast. Additional differentially expressed elements such as L1P and various MER transposons also exhibited a similar pattern. Finally, our repeat enrichment analysis on the promoters of differentially expressed genes revealed further links between additional repeats and nearby genes. (C) 2019 Elsevier Inc. All rights reserved.
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    Article
    Expressions of the Satellite Repeat Hsat5 and Transposable Elements Are Implicated in Disease Progression and Survival in Glioma
    (Tubitak Scientific & Technological Research Council Turkey, 2024-08-23) Köse, Sıla Naz; Yaraş, Tutku; Bursalı, Ahmet; Oktay, Yavuz; Yandım, Cihangir; Karakulah, Gökhan
    The glioma genome encompasses a complex array of dysregulatory events, presenting a formidable challenge in managing this devastating disease. Despite the widespread distribution of repeat and transposable elements across the human genome, their involvement in glioma's molecular pathology and patient survival remains largely unexplored. In this study, we aimed to characterize the links between the expressions of repeat/transposable elements with disease progression and survival in glioma patients. Hence, we analyzed the expression levels of satellite repeats and transposons along with genes in low-grade glioma (LGG) and high-grade glioma (HGG). Endogenous transposable elements LTR5 and HERV_a-int exhibited higher expression in HGG patients, along with immune response-related genes. Altogether, 16 transposable elements were associated with slower progression of disease in LGG patients. Conversely, 22 transposons and the HSAT5 satellite repeat were linked to a shorter event-free survival in HGG patients. Intriguingly, our weighted gene coexpression network analysis (WGCNA) disclosed that the HSAT5 satellite repeat resided in the same module network with genes implicated in chromosome segregation and nuclear division; potentially hinting at its contribution to disease pathogenesis. Collectively, we report for the first time that repeat and/or transposon expression could be related to disease progression and survival in glioma. The expressions of these elements seem to exert a protective effect during LGG-to-HGG progression, whereas they could have a detrimental impact once HGG is established. The results presented herein could serve as a foundation for further experimental work aimed at elucidating the molecular regulation of glioma genome.
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    Article
    Citation - WoS: 7
    Citation - Scopus: 8
    Signature Changes in the Expressions of Protein-Coding Genes, Lncrnas, and Repeat Elements in Early and Late Cellular Senescence
    (Tubitak Scientific & Technical Research Council Turkey, 2020-12-14) Karakulah, Gokhan; Yandim, Cihangir
    Replicative cellular senescence is the main cause of aging. It is important to note that early senescence is linked to tissue regeneration, whereas late senescence is known to trigger a chronically inflammatory phenotype. Despite the presence of various genome-wide studies, there is a lack of information on distinguishing early and late senescent phenotypes at the transcriptome level. Particularly, the changes in the noncoding RNA portion of the aging cell have not been fully elucidated. By utilising RNA sequencing data of fibroblasts, hereby, we are not only reporting changes in gene expression profiles and relevant biological processes in the early and late senescent phenotypes but also presenting significant differences in the expressions of many unravelled long noncoding RNAs (lncRNAs) and transcripts arisen from repetitive DNA. Our results indicate that, in addition to previously reported L1 elements, various LTR and DNA transposons, as well as members of the classical satellites including HSAT5 and alpha-satellites (ALR/Alpha), are expressed at higher levels in late senescence. Moreover, we revealed finer links between the expression levels of repeats with the genes located near them and known to be involved in cell cycle and senescence. Noncoding elements reported here provide a new perspective to be explored in further experimental studies.
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    Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Thyroid Hormone T3 Augments the Cytotoxicity of Sorafenib in Huh7 Hepatocellular Carcinoma Cells by Suppressing Akt Expression
    (Wolters Kluwer Medknow Publications, 2023-04-05) Uyulgan, S.; Köse, S.N.; Kıpçak, A.; Başkan, Y.; Dağlar, G.; Karagonlar, Z.F.; Yandım, C.; Kose, Sila Naz; Koese, Sila Naz
    Background and Objectives: Hepatocellular carcinoma (HCC) is a primary cancer that poorly responds to treatment. Molecular cancer studies led to the development of kinase inhibitors, among which sorafenib stands out as a multi-kinase inhibitor approved by FDA for first line use in HCC patients. However, the efficiency of sorafenib was shown to be counteracted by numerous subcellular pathways involving the effector kinase AKT, causing resistance and limiting its survival benefit. On the way of breaking such resistance mechanisms and increase the efficiency of sorafenib, deeper understanding of hepatocellular physiology is essential. Thyroid hormones were shown to be metabolized in liver and inevitably affect the molecular behaviour of hepatocytes. Interestingly, thyroid hormone T3 was also demonstrated to be potentially influential in liver regeneration and treatment with this hormone reportedly led to a decrease in HCC tumor growths. In this study, we aimed to uncover the impact of T3 hormone on the cytotoxic response to sorafenib in HCC in vitro. Materials and Methods: We pre-treated the HCC cell line Huh-7 with T3 prior to sorafenib exposure both in 2D and 3D culture. We checked cell viability with MTT assay in 2D culture and measured the sizes of 3D spheroids with bright-field microscopy followed by a surface analysis with ImageJ. We also performed scratch assay to measure cell migration as well as western blot and qPCR to uncover affected pathways. Results: We observed an additive effect to sorafenib’s cytotoxicity both in 2D and 3D culture. Cell migration assay also confirmed our finding and pointed out a benefit of T3 hormone in HCC cell migration. Western blot experiments showed that T3 exerts its additive effect by suppressing AKT expression upon sorafenib treatment both at protein and gene expression levels. Conclusion: Our results open a promising new avenue in increasing sorafenib’s cytotoxicity where thyroid hormone T3 is utilized to modulate AKT expression to combat resistance, and warrant further studies in the field. © 2024 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow.
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    Master Thesis
    İnsan Meme Epitel Hücrelerindeki Replikatif Yaşlanma Sürecinde Sıcak Mutasyon Bölgelerinin ve Klonal Evrimin Genom Genelinde Belirlenmesi
    (2025) Turan, Elif; Yandım, Cihangir
    Replikatif hücresel yaşlanma, yaşlanmanın temel belirteçlerinden biri olup birçok yaşa bağlı hastalığa katkıda bulunmaktadır. Sporadik yaşa bağlı kanserlerin büyük çoğunluğunun epitel dokulardan kaynaklanması nedeniyle, epitel hücre yaşlanması sırasında ortaya çıkan genomik değişikliklerin ve bu değişimlerin klonal yapılara etkisinin anlaşılması büyük önem taşır İnsan meme epitel hücreleri (HMEC), epitel dokularda replikatif yaşlanmanın in vitro incelenmesi için altın standart kabul edilen bir modeldir. Bu tez çalışmasında, replikatif yaşlanmaya ulaşan HMEC hücrelerinin genomik DNA'sında oluşan tüm değişiklikleri, genç ve çoğalmakta olan karşıtlarıyla karşılaştırmalı olarak ortaya koymak amacıyla derin kısa-okuma tüm genom dizileme teknolojisi kullanılmıştır. Tek nükleotid varyasyonları, indeller, yapısal değişiklikler ve kopya sayısı değişimleri gibi yaşa bağlı geniş bir varyasyon yelpazesi tanımlanmış; klonal evrimsel dinamikler ileri düzey biyoinformatik yöntemlerle incelenmiştir. Sonuçlar, replikatif yaşlanmanın doğrusal bir klonal evrim izlediğini ve baskın klonların ardışık olarak ortaya çıkıp mutasyon biriktirdiğini göstermiştir. Mutasyona uğramış genler, morfogenez, hücre iskeleti organizasyonu ve metabolizma ile ilişkili yolaklarda zenginleşmiş olup, belirleyici moleküler değişimlere işaret etmektedir. Perisentromerik bölgeler, telomerik ve subtelomerik bölgelerle birlikte daha önce yeterince tanınmamış genomik sıcak noktalar olarak ortaya çıkmıştır. Mutasyonel imza analizleri, yaşa ve kansere özgü imzaların yaşlı hücrelerde güçlü şekilde zenginleştiğini doğrulamıştır. Birey içi benzerlik gözlenmesine rağmen, mutasyon birikimi aynı zamanda rastlantısal farklılıklar da göstermiş; bu da hem belirleyici hem de stokastik süreçlerin etkili olduğunu ortaya koymuştur. Bu bulgular, replikatif yaşlanmanın genom düzeyindeki yapısını ortaya koymakta ve yaşlanmaya bağlı işlev kaybı ile kanserleşme sürecine olası katkısını aydınlatmaktadır. Gelecek çalışmalarda, çoklu örnekli klonal modelleme ve uzun okuma dizileme ile, tekrar eden bölgelerdeki yapısal değişiklikleri daha net çözümlemek planlanmaktadır.
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    Article
    Citation - WoS: 41
    Citation - Scopus: 41
    Expression Dynamics of Repetitive Dna in Early Human Embryonic Development
    (Bmc, 2019-05-31) Yandim, Cihangir; Karakulah, Gokhan
    Background: The last decade witnessed a number of genome-wide studies on human pre-implantation, which mostly focused on genes and provided only limited information on repeats, excluding the satellites. Considering the fact that repeats constitute a large portion of our genome with reported links to human physiology and disease, a thorough understanding of their spatiotemporal regulation during human embryogenesis will give invaluable clues on chromatin dynamics across time and space. Therefore, we performed a detailed expression analysis of all repetitive DNA elements including the satellites across stages of human pre-implantation and embryonic stem cells. Results: We uncovered stage-specific expressions of more than a thousand repeat elements whose expressions fluctuated with a mild global decrease at the blastocyst stage. Most satellites were highly expressed at the 4-cell level and expressions of ACRO1 and D20S16 specifically peaked at this point. Whereas all members of the SVA elements were highly upregulated at 8-cell and morula stages, other transposons and small RNA repeats exhibited a high level of variation among their specific subtypes. Our repeat enrichment analysis in gene promoters coupled with expression correlations highlighted potential links between repeat expressions and nearby genes, emphasising mostly 8-cell and morula specific genes together with SVA_D, LTR5_Hs and LTR70 transposons. The DNA methylation analysis further complemented the understanding on the mechanistic aspects of the repeatome's regulation per se and revealed critical stages where DNA methylation levels are negatively correlating with repeat expression. Conclusions: Taken together, our study shows that specific expression patterns are not exclusive to genes and longnon-coding RNAs but the repeatome also exhibits an intriguingly dynamic pattern at the global scale. Repeats identified in this study; particularly satellites, which were historically associated with heterochromatin, and those with potential links to nearby gene expression provide valuable insights into the understanding of key events in genomic regulation and warrant further research in epigenetics, genomics and developmental biology.