Molecular carcinogenesis studies aim to dissect the molecular aspects of cancer initiation and progression and use this information to develop more effective treatments and prevention strategies. Today, molecular mechanisms associated with different cancers are partly being deciphered by functional genomics strategies, leading to translational research-supported novel discoveries of potential therapeutic stratifications designed to counteract or actually reverse such mechanisms. As a molecular carcinogenesis and functional genomics laboratory, we adapt traditional molecular cancer biology and classical biochemical approaches to next generation technologies (e.g. genome engineering and high-throughput functional screening platforms) and aim to implement an ideal research environment for identification and development of targeted cancer therapies. Our ambition is to advance knowledge on carcinogenesis mechanisms and explore drug targets for cancer.
Overall goal is to pursue a research program that utilizes functional genomics approaches and state-of-the-art tools for the understanding and the unraveling of cellular and molecular underpinnings of carcinogenesis and develops effective strategies for the discovery of cancer vulnerabilities, and hence potential future cancer drug targets. In this context, we are interested in the following research themes: (i) understanding why and how non-small cell lung cancer (NSCLC) cells become resistant to targeted therapies, (ii) mapping out cancer cell essential genes and dependencies across cancer types using functional genomics screens, (iii) understanding and mining of the molecular mechanisms of cancer cell senescence and identifying novel druggable cellular targets in senescence-resistance.
In order to do so, our lab is adopting the most comprehensive tools and relevant models for the examination of biological pathways and disease pathobiology.
We undertake a wide range of research efforts focused on the following major areas of investigation: (1) identification and characterization of the mechanisms driving cancer; (2) druggable target identification and validation against such mechanisms. The close proximity to basic and translational research for interdisciplinary collaboration is invaluable in the selection and validation of novel cancer drug discovery targets. Our lab is at the center of characterization of cancer-specific vulnerabilities using high-throughput data combined with information on genomic abnormalities in order to increase research opportunities and support improved treatment of such diseases.
Ece Cakiroglu, Serif Senturk. Genomics and Functional Genomics of Malignant Pleural Mesothelioma. International Journal of Molecular Sciences. 2020 September ; 21 (17) : E6342. doi:10.3390/ijms21176342.
Soheil Akbari, Nur Arslan, Şerif Şentürk, Esra Erdal. Next-Generation Liver Medicine Using Organoid Models. Frontiers in Cell and Developmental Biology-Stem Cell Research. 2019 December ; 7 : 345. doi:10.3389/fcell.2019.00345.
Aysim Gunes, Ezgi Bagirsakci, Evin Iscan, Gulcin Cakan-Akdogan, Umut Aykutlu, Serif Senturk, Gunes Ozhan, Esra Erdal, Deniz Nart, Funda Yilmaz Barbet, Nese Atabey. Thioredoxin interacting protein promotes invasion in hepatocellular carcinoma. Oncotarget. 2018 ; 9 (96) : 36849-36866. doi:10.18632/oncotarget.26402.
Senturk S, Shirole NH, Nowak DG, Corbo V, Pal D, Vaughan A, Tuveson DA, Trotman LC, Kinney JB, Sordella R. Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization. Nature communications. 2017 February ; 8 : 14370. doi:10.1038/ncomms14370.
Shirole NH, Pal D, Kastenhuber ER, Senturk S, Boroda J, Pisterzi P, Miller M, Munoz G, Anderluh M, Ladanyi M, Lowe SW, Sordella R. TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions. eLife. 2016 October ; 5 : e17929. doi:10.7554/eLife.25532.
Nowak DG, Cho H, Herzka T, Watrud K, DeMarco DV, Wang VM, Senturk S, Fellmann C, Ding D, Beinortas T, Kleinman D, Chen M, Sordella R, Wilkinson JE, Castillo-Martin M, Cordon-Cardo C, Robinson BD, Trotman LC. MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2.. Cancer discovery. 2015 June ; 5 (6) : 636-51. doi:10.1158/2159-8290.CD-14-1113.
Senturk S, Yao Z, Camiolo M, Stiles B, Rathod T, Walsh AM, Nemajerova A, Lazzara MJ, Altorki NK, Krainer A, Moll UM, Lowe SW, Cartegni L, Sordella R. p53Ψ is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state.. Proceedings of the National Academy of Sciences of the United States of America. 2014 August ; 111 (32) : E3287-96. doi:10.1073/pnas.1321640111.
Mender I, Senturk S, Ozgunes N, Akcali KC, Kletsas D, Gryaznov S, Can A, Shay JW, Dikmen ZG. Imetelstat (a telomerase antagonist) exerts off‑target effects on the cytoskeleton.. International journal of oncology. 2013 May ; 42 (5) : 1709-15. doi:10.3892/ijo.2013.1865.
Sucularli C, Senturk S, Ozturk M, Konu O. Dose- and time-dependent expression patterns of zebrafish orthologs of selected E2F target genes in response to serum starvation/replenishment.. Molecular biology reports. 2011 August ; 38 (6) : 4111-23. doi:10.1007/s11033-010-0531-2.
Buontempo F, Ersahin T, Missiroli S, Senturk S, Etro D, Ozturk M, Capitani S, Cetin-Atalay R, Neri ML. Inhibition of Akt signaling in hepatoma cells induces apoptotic cell death independent of Akt activation status.. Investigational new drugs. 2011 December ; 29 (6) : 1303-13. doi:10.1007/s10637-010-9486-3.
Mumcuoglu M, Bagislar S, Yuzugullu H, Alotaibi H, Senturk S, Telkoparan P, Gur-Dedeoglu B, Cingoz B, Bozkurt B, Tazebay UH, Yulug IG, Akcali KC, Ozturk M. The ability to generate senescent progeny as a mechanism underlying breast cancer cell heterogeneity.. PloS one. 2010 June ; 5 (6) : e11288. doi:10.1371/journal.pone.0011288.
Senturk S, Mumcuoglu M, Gursoy-Yuzugullu O, Cingoz B, Akcali KC, Ozturk M. Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth.. Hepatology (Baltimore, Md.). 2010 September ; 52 (3) : 966-74. doi:10.1002/hep.23769.
Yuzugullu H, Benhaj K, Ozturk N, Senturk S, Celik E, Toylu A, Tasdemir N, Yilmaz M, Erdal E, Akcali KC, Atabey N, Ozturk M. Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells.. Molecular cancer. 2009 October ; 8 : 90. doi:10.1186/1476-4598-8-90.
Ozturk M, Arslan-Ergul A, Bagislar S, Senturk S, Yuzugullu H. Senescence and immortality in hepatocellular carcinoma.. Cancer letters. 2009 December ; 286 (1) : 103-13. doi:10.1016/j.canlet.2008.10.048.
Ozturk N, Erdal E, Mumcuoglu M, Akcali KC, Yalcin O, Senturk S, Arslan-Ergul A, Gur B, Yulug I, Cetin-Atalay R, Yakicier C, Yagci T, Tez M, Ozturk M. Reprogramming of replicative senescence in hepatocellular carcinoma-derived cells.. Proceedings of the National Academy of Sciences of the United States of America. 2006 February ; 103 (7) : 2178-83. doi:10.1073/pnas.0510877103.
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Inducible CRISPR-based Genome Editing for the Characterization of Cancer Genes (2018). Genome Editing and Engineering: From TALENs, ZFNs and CRISPRs to Molecular Surgery. Cambridge University Press.
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