Researcher:
Kala, Ezgi Yağmur

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PhD Student

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Ezgi Yağmur

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Kala

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Kala, Ezgi Yağmur

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2020 - 20222

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Researcher Of Publications: search.filters.isAuthorOfPublication.6cccbbde-16b6-4cae-945a-9f25ed99f28c

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    PublicationOpen Access
    EPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform, to identify cancer-specific epigenetic vulnerabilities
    (Nature Portfolio, 2022) Philpott, Martin; Cribbs, Adam P.; Kung, Sonia H.Y; Bayram, Özlem Yedier; Gökbayrak, Bengül; Kayabölen, Alişan; Aksu, Ali Cenk; Cavga, Ayşe Derya; Cingöz, Ahmet; Kala, Ezgi Yağmur; Karabıyık, Göktuğ; Esin, Beril; Morova, Tunç; Uyulur, Fırat; Önder, Tuğba Bağcı; Syed, Hamzah; Lack, Nathan Alan; Önder, Tamer Tevfik; PhD Student; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 184359; 318138; 120842; 42946
    Dysregulation of the epigenome due to alterations in chromatin modifier proteins commonly contribute to malignant transformation. To interrogate the roles of epigenetic modifiers in cancer cells, we generated an epigenome-wide CRISPR-Cas9 knockout library (EPIKOL) that targets a wide-range of epigenetic modifiers and their cofactors. We conducted eight screens in two different cancer types and showed that EPIKOL performs with high efficiency in terms of sgRNA distribution and depletion of essential genes. We discovered novel epigenetic modifiers that regulate triple-negative breast cancer (TNBC) and prostate cancer cell fitness. We confirmed the growth-regulatory functions of individual candidates, including SS18L2 and members of the NSL complex (KANSL2, KANSL3, KAT8) in TNBC cells. Overall, we show that EPIKOL, a focused sgRNA library targeting similar to 800 genes, can reveal epigenetic modifiers that are essential for cancer cell fitness under in vitro and in vivo conditions and enable the identification of novel anti-cancer targets. Due to its comprehensive epigenome-wide targets and relatively high number of sgRNAs per gene, EPIKOL will facilitate studies examining functional roles of epigenetic modifiers in a wide range of contexts, such as screens in primary cells, patient-derived xenografts as well as in vivo models.
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    PublicationOpen Access
    Development of gene editing strategies for human beta-globin (HBB) gene mutations
    (Elsevier, 2020) Yüce, Melek; Alpaslan, Medine Karadağ; Kocabaş, Fatih; Kalkan, Batuhan Mert; Kala, Ezgi Yağmur; PhD Student; Faculty Member; Graduate School of Health Sciences
    Recent developments in gene editing technology have enabled scientists to modify DNA sequence by using engineered endonucleases. These gene editing tools are promising candidates for clinical applications, especially for treatment of inherited disorders like sickle cell disease (SCD). SCD is caused by a point mutation in human beta-globin gene (HBB). Clinical strategies have demonstrated substantial success, however there is not any permanent cure for SCD available. CRISPR/Cas9 platform uses a single endonuclease and a single guide RNA (gRNA) to induce sequence-specific DNA double strand break (DSB). When this accompanies a repair template, it allows repairing the mutated gene. In this study, it was aimed to target HBB gene via CRISPR/Cas9 genome editing tool to introduce nucleotide alterations for efficient genome editing and correction of point mutations causing SCD in human cell line, by Homology Directed Repair (HDR). We have achieved to induce target specific nucleotide changes on HBB gene in the locus of mutation causing SCD. The effect of on-target activity of bone fide standard gRNA and newly developed longer gRNA were examined. It is observed that longer gRNA has higher affinity to target DNA while having the same performance for targeting and Cas9 induced DSBs. HDR mechanism was triggered by co-delivery of donor DNA repair templates in circular plasmid form. In conclusion, we have suggested methodological pipeline for efficient targeting with higher affinity to target DNA and generating desired modifications on HBB gene.