Researcher: Önder, Tuğba Bağcı
Name Variants
Önder, Tuğba Bağcı
Email Address
Birth Date
52 results
Search Results
Now showing 1 - 10 of 52
Publication Metadata only Editorial expression of concern: generation of TRAIL-resistant cell line models reveals distinct adaptive mechanisms for acquired resistance and re-sensitization(Springer Nature, 2024) Esai Selvan, Myvizhi; Bhere, Deepak; Shah, Khalid.; Cingöz, Ahmet; Özyerli, Ezgi; Gümüş, Zeynep Hülya; Solaroğlu, İhsan; Önder, Tuğba Bağcı; Morova, Tunç; Şeker-Polat, Fidan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of Medicine;Editorial Expression of Concern to: Oncogenehttps://doi.org/10.1038/s41388-021-01697-6, published online 25 March 2021 The Editors-in-Chief would like to alert the readers that concerns have been raised regarding some of the figures presented in this article [1]. Specifically: The DR5 abd H3 western blot images in Fig. 4A and F (top) appear to overlap; In Fig. 6B, the red channels of MSC-GFP A172-S and A172-R appear highly similar; In Fig. 6E, the representative panels from mouse bioluminescence images from two different time points (d3/A172-R/GFP and d7/A172-R/TRAIL) appear highly similar. The DR5 abd H3 western blot images in Fig. 4A and F (top) appear to overlap; In Fig. 6B, the red channels of MSC-GFP A172-S and A172-R appear highly similar; In Fig. 6E, the representative panels from mouse bioluminescence images from two different time points (d3/A172-R/GFP and d7/A172-R/TRAIL) appear highly similar. The authors have provided the raw data pertaining to Figs. 4A, 4F and 6B and stated that the errors in the panels in question occurred during manuscript preparation inadvertently. The conclusions of these figures remain unchanged. However, the original images for Fig. 6E are no longer available. Readers are therefore advised to interpret these results with caution. All authors agree to this Editorial Expression of Concern. © Springer Nature Limited 2024.Publication Open Access ACE2-decorated virus-like particles effectively block SARS-CoV-2 infection(Dove Medical Press Ltd, 2024) Supramaniam, Aroon; Idris, Adi; Bayraktar, Canan; Kayabölen, Alişan; Odabaş, Arda; Durgun, Ayşegül; Kök, İpek; Sevinç, Kenan; Önder, Tuğba Bağcı; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of MedicinePurpose: Over the past three years, extensive research has been dedicated to understanding and combating COVID-19. Targeting the interaction between the SARS-CoV-2 Spike protein and the ACE2 receptor has emerged as a promising therapeutic strategy against SARS-CoV-2. This study aimed to develop ACE2-coated virus-like particles (ACE2-VLPs), which can be utilized to prevent viral entry into host cells and efficiently neutralize the virus. Methods: Virus-like particles were generated through the utilization of a packaging plasmid in conjunction with a plasmid containing the ACE2 envelope sequence. Subsequently, ACE2-VLPs and ACE2-EVs were purified via ultracentrifugation. The quantification of VLPs was validated through multiple methods, including Nanosight 3000, TEM imaging, and Western blot analysis. Various packaging systems were explored to optimize the ACE2-VLP configuration for enhanced neutralization capabilities. The evaluation of neutralization effectiveness was conducted using pseudoviruses bearing different spike protein variants. Furthermore, the study assessed the neutralization potential against the Omicron BA.1 variant in Vero E6 cells. Results: ACE2-VLPs showed a high neutralization capacity even at low doses and demonstrated superior efficacy in in vitro pseudoviral assays compared to extracellular vesicles carrying ACE2. ACE2-VLPs remained stable under various environmental temperatures and effectively blocked all tested variants of concern in vitro. Notably, they exhibited significant neutralization against Omicron BA.1 variant in Vero E6 cells. Given their superior efficacy compared to extracellular vesicles and proven success against live virus, ACE2-VLPs stand out as crucial candidates for treating SARS-CoV-2 infections. Conclusion: This novel therapeutic approach of coating VLPs with receptor particles provides a proof-of-concept for designing effective neutralization strategies for other viral diseases in the future.Publication Metadata only New trends in cell death: overview of the International Society of Cell Death (ICDS) annual meeting in Johannesburg South Africa (May 19-22, 2023)(BMC, 2024) Cronje, Marianne J.; Gadiyar, Varsha; Chipuk, Jerry Edward; Krysko, Dmitri; Birge, Raymond B.; Lockshin, Richard A.; Zakeri, Zahra; Önder, Tuğba Bağcı; School of MedicinePublication Metadata only Exploiting epigenetic targets to overcome taxane resistance in prostate cancer(Springernature, 2024) Department of Molecular Biology and Genetics; Department of Molecular Biology and Genetics; Cevatemre, Buse; Bulut, İpek; Dedeoğlu, Beyza; Işıklar, Arda; Syed, Hamzah; Bayram, Özlem Yedier; Önder, Tuğba Bağcı; Ayhan, Ceyda Açılan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of Medicine; College of EngineeringThe development of taxane resistance remains a major challenge for castration resistant prostate cancer (CR-PCa), despite the effectiveness of taxanes in prolonging patient survival. To uncover novel targets, we performed an epigenetic drug screen on taxane (docetaxel and cabazitaxel) resistant CR-PCa cells. We identified BRPF reader proteins, along with several epigenetic groups (CBP/p300, Menin-MLL, PRMT5 and SIRT1) that act as targets effectively reversing the resistance mediated by ABCB1. Targeting BRPFs specifically resulted in the resensitization of resistant cells, while no such effect was observed on the sensitive compartment. These cells were successfully arrested at the G2/M phase of cell cycle and underwent apoptosis upon BRPF inhibition, confirming the restoration of taxane susceptibility. Pharmacological inhibition of BRPFs reduced ABCB1 activity, indicating that BRPFs may be involved in an efflux-related mechanism. Indeed, ChIP-qPCR analysis confirmed binding of BRPF1 to the ABCB1 promoter suggesting direct regulation of the ABCB1 gene at the transcriptional level. RNA-seq analysis revealed that BRPF1 knockdown affects the genes enriched in mTORC1 and UPR signaling pathways, revealing potential mechanisms underlying its functional impact, which is further supported by the enhancement of taxane response through the combined inhibition of ABCB1 and mTOR pathways, providing evidence for the involvement of multiple BRPF1-regulated pathways. Beyond clinical attributes (Gleason score, tumor stage, therapy outcome, recurrence), metastatic PCa databases further supported the significance of BRPF1 in taxane resistance, as evidenced by its upregulation in taxane-exposed PCa patients.Publication Metadata only CRISPRa-mediated induction of apoptosis in therapy-resistant glioblastoma cells via derepression of pro-apoptotic genes(Amer Assoc Cancer Research, 2022) Yılmaz, Ebru; Kayabölen, Alişan; Atalar, Semra Cemre; Ulukan, Bürge; Zeybel, Müjdat; Önder, Tuğba Bağcı; Graduate School of Health Sciences; School of MedicinePublication Metadata only Investigation of ionizing radiation response in new resistance models of glioblastoma.(Amer Assoc Cancer Research, 2021) N/A; N/A; Değirmenci, Nareg Pınarbaşı; Önder, Tuğba Bağcı; Sur, İlknur Erdem; Selek, Uğur; PhD Student; Faculty Member; Faculty Member; 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; School of Medicine; School of Medicine; N/A; 184359; N/A; 27211N/APublication Metadata only Epigenetic modifications of androgen receptor signaling in castration resistant prostate cancer (CRPC)(Elsevier Sci Ltd, 2014) Saraç, Hilal; Toparlak, Ömer Duhan; Kaplan, Anıl; Ebrahimi, Ayyub A.; Önder, Tuğba Bağcı; Önder, Tamer Tevfik; Lack, Nathan Alan; PhD Student; Other; Undergraduate Student; Researcher; Faculty Member; Faculty Member; Faculty Member; Graduate School of Sciences and Engineering; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; N/A; N/A; N/A; 381072; 184359; 42946; 120842Introduction: Prostate cancer is one of the most common forms of cancer in Turkish and European men. For those patients with late-stage prostate cancer, androgen depletion therapy is current standard treatment. While initially successful, almost all patients eventually develop resistance against this treatment. Once the cancer reaches this advanced, progressive form, it is termed castration resistant prostate cancer (CRPC). Whereas the progression mechanisms of CRPC are poorly understood, it has been shown that in CRPC patients, the androgen receptor (AR) is still active despite undetectable androgen levels. Since AR signaling is important in the progression and growth of prostate cancer, understanding how AR mediated signaling occurs in CRPC is critical to more efficient treatment of this recurrent disease. Material and Methods: There are several possible causes for this conversion from androgen-sensitive to androgen-independent prostate cancer. Previous work has demonstrated that epigenetic modifiers such as EZH2 and LSD1 can mediate the sensitization of androgen receptor in CRPC. However, only a small subset of epigenetic modifiers has been characterized. To better understand the role of histone modification on CRPC, we conducted a large scale shRNA screen of epigenetic modifying enzymes to identify those genes that prevent androgen-independent growth. Results and Discussion: From this screen several hit genes have been found that cause a reversion of androgen-independent to androgen-dependent prostate cancer. The shRNA knock-down of these hit genes was confirmed by western blot and qRT-PCR. We are currently characterizing how these epigenetic modifiers affect androgen-receptor mediated signalling. Conclusion: These results will offer new insight into the role of epigenetic modifiers in nuclear receptor signalling.Publication Metadata only Directing chemiluminescent dioxetanes to mitochondria: a cationic luminophore enables in vitro and in vivo detection of cancer cells upon enzymatic activation(Elsevier B.V., 2023) Department of Chemistry; N/A; N/A; Department of Chemistry; N/A; N/A; N/A; N/A; N/A; Department of Chemistry; Department of Chemistry; Gündüz, Hande; Acari, Alperen; Çetin, Sultan; Almammadov, Toghrul; Değirmenci, Nareg Pınarbaşı; Dırak, Musa; Cingöz, Ahmet; Kılıç, Eda; Önder, Tuğba Bağcı; Kölemen, Safacan; Researcher; Master Student; PhD Student; Researcher; PhD Student; PhD Student; Researcher; Master Student; Faculty Member; Faculty Member; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; College of Sciences; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; N/A; Graduate School of Sciences and Engineering; School of Medicine; College of Sciences; 224496; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 184359; 272051A mitochondrion targeted and leucine aminopeptidase (LAP) activatable 1,2-dioxatane based chemiluminescent probe (MCL) for detection of LAP activity in living cancer cells and tumor bearing mice was reported. MCL displayed a selective and sensitive turn-on response in aqueous solutions upon reacting with the LAP enzyme. In cell culture studies, a selective luminescence intensity increase was observed in cancer cell lines, suggesting that MCL can differentiate between cancer and normal cells and allows detection of varying endogenous LAP concentrations. Using fluorescence imaging with a commercial Mitotracker dye, MCL was also shown to localize mitochondria in cancer cell lines. Furthermore, MCL was used to image tumors in mice models. MCL marks not only the first ever example of a mitochondria targeted chemiluminescent probe, but also the first ever example of an organelle targeted 1,2-dioxetane derivative. © 2023 Elsevier B.V.Publication Metadata only Assessment of the MRI and behavioral test results in a focal cerebral ischemia-reperfusion model in the rat after separate and combined use of mouse-derived neural progenitor cells, human-derived neural progenitor cells and atorvastatin(Turkish Neurosurgical Soc, 2018) Tanta, Alican; Izgi, Nail; Erdag, Ece; Aras, Yavuz; Genc, Cetin; N/A; Önder, Tuğba Bağcı; Faculty Member; School of Medicine; 184359AIM: To assess the efficacy of Neural progenitor cell (NPC) transplantation in ischemic stroke, and to investigate whether atorvastatin enhances therapeutic potency of NPC after stroke. MATERIAL and METHODS: The focal cerebral ischemia-reperfusion model was performed by transient occlusion of middle cerebral artery. Rats were assigned randomly to receive intracerebral transplantation of mouse NPC alone (mNPC), human NPC alone (hNPC), mouse NPC plus oral atorvastatin (mNPC+A), human NPC plus oral atorvastatin (hNPC+A), oral atorvastatin alone, or intracerebral Dulbecco's Modified Eagle's medium injection (control group). Adhesive removal, rotarod, cylinder tests, and magnetic resonance imaging (MRI) were used for assessment of rats during 4 weeks. After sacrification on 28th day, rats were investigated by immunofluorescent staining. RESULTS: The hNPC and mNPC groups showed significantly improved functional outcome and reduced infarct area ratio compared with the control group. The hNPC group had significantly better performance and lower infarct area ratio than the mNPC group. Addition of atorvastatin to stem cell therapy significantly improved functional outcome, although it did not affect the infarct area ratio on MRI. Anti-inflammatory response in the infarct area was higher in the mNPC group. NPC transplantation significantly reduced the amount of microglia and a significant increase in the amount of astrocytes. CD8a+ T lymphocyte and granzyme B activities were not detected in any of the subjects. CONCLUSION: Both hNPC and mNPC treatments significantly improved functional outcome, and reduced infarct area ratio after stroke. Atorvastatin enhanced the therapeutic potency of NPCs, including neurological improvement.Publication Metadata only A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells(Wiley, 2017) Adiguzel, Zelal; Ozalp-Yaman, Seniz; Celik, Gokalp; Salem, Safia; Cetin, Yuksel; Acilan, Ceyda; N/A; N/A; Önder, Tuğba Bağcı; Şenbabaoğlu, Filiz; Faculty Member; PhD Student; School of Medicine; Graduate School of Health Sciences; 184359; N/AHere, we describe the characteristics of a Pt-blue complex [Pt-4(2-atp)(8)(H2O)(OH)] (2-atp: 2-aminothiophenol) as a prodrug for its DNA-binding properties and its use in cancer therapy. The nature of the interaction between the Pt-blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single- and double-stranded breaks (DBS) on DNA in vitro, but no DSBs in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species (ROS) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST-1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro-apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt-blue complex under study grants premise for further studies.