Şerif Şentürk Laboratory

 

Şerif Şentürk serif.senturk@deu.edu.tr
Members
Ayça Zeybek Kuyucu, Post-doc
Ece Çakıroğlu, PhD Student
Yağmur Toktay, MSc Student
Asli Kurden Pekmezci, MSc Student
Bahar Bingöl, Technician

 

OVERVIEW

Translational research is an interdisciplinary branch of the biomedical field which aims to facilitate the application of fundamental discoveries of basic science into medical practices in order to enhance human health and well-being. Translational research implements a “bench-to-bedside” vision, harnessing the knowledge of basic science and preclinical studies with the ultimate goal to develop promising novel therapeutics and treatment options that can be used clinically and are able to be commercialized. Today, molecular alterations associated with different diseases are being deciphered by basic research studies, leading to translational research-supported discovery of new therapeutic agents designed to counteract or actually reverse such alterations. As a centre of excellence laboratory for basic and translational cancer research, we aim to provide an ideal environment with state-of-the-art platforms for target discovery and the development of targeted therapies for the treatment of cancer. Our ambition is to advance knowledge and innovation with the future goal to deliver preclinical drug candidate molecules for progression into the clinic.

RESEARCH INTERESTS

Our lab is aiming to establish a translational research niche fostered by biological discovery activities of basic research. In this context, we are interested in three linked, broad and long-term themes: (i) identifying and validating novel “druggable” cellular targets across cancer types, (ii) discovering and developing innovative biological drugs (mainly, but not limited to, therapeutic monoclonal antibodies, mAbs) against such targets in the field of oncology by focusing on anti-proliferative and immunotherapy mechanisms and (iii) developing and producing “biosimilar” and “bio better” versions of already approved original biological medicines. In order to do so, our lab is interested in developing the most comprehensive and relevant models for the examination of biological pathways and disease pathobiology.

  1. Future drug targets are expected to emerge from high-throughput functional genomics screening technologies supported by genetic engineering tools and analysis approaches that identify the mechanisms regulating biological processes. Therefore, our lab is interested in utilizing RNAi and CRISPR/Cas9 technology in-vitro and in vivo as the “discovery engine” of genome-wide screening libraries to uncover cancer-specific vulnerabilities. Here, we are going to perform pooled screens using lentivirus-based mechanisms for sgRNA delivery and Cas9 expression as well as shRNA expression.
  2. Conventional production of monoclonal antibodies involves in vitro and in vivo procedures. Here, potentially druggable molecule identification will be followed by immunogen production and mouse immunization, hence mAb development in antibody-producing B cells. These B lymphocytes will then be fused with myeloma fusion partners to generate immortalized hybrid somatic cells, a hybridoma cell line capable of producing high-quality antibodies. Systematic screening and characterization of therapeutic mAbs-secreting hybridomas will be performed for their capability to block the activity of target molecules/pathways and hence the proliferation of cancer cells. Candidate molecules will be humanized by the replacement of mouse constant and V framework regions for human sequences and expression of these constructs in mammalian cell cultures.
  3. Biologics are today’s most important therapeutic agents and valuable life-saving medicines with profound impact on many medical fields primarily oncology, but also cardiology, neurology, immunology and others. They are manufactured in and extracted from genetically engineered living systems through the use of biotechnology, such as recombinant DNA technology, controlled gene expression, or antibody technologies. A similar biologic or biosimilar drug, much like generic drugs, is a less costly version of an originator biological product. Yet, biosimilars meet extremely high standards for quality, safety, efficacy, and comparability or similarity to the reference biologic and can only be manufactured when the original product’s patent expires. In this context, our lab is interested in developing biosimilar versions of original biologics which is a robust process that requires science-based and data-intensive steps in order to ensure that there is no clinically meaningful difference between the biosimilar and the reference product.

RESEARCH HIGHLIGHTS

We undertake a wide range of significant research fields 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 expertise 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.

Lab members:

Senturk lab is currently seeking highly motivated graduate students, postdoctoral fellows, and specialists. If you are interested, please contact us by email serif.senturk@deu.edu.tr

Education/Research Experience
November 2015 – present Assistant Professor
Dokuz Eylul University, Izmir Biomedicine and Genome Institute (iBG-izmir), Izmir, TURKEY.
2010 – 2015 Postdoctoral fellow
Cancer Center, Signal Transduction Laboratory
Cold Spring Harbor Laboratory, New York, USA.
2003 – 2010 Combined PhD. in Molecular Biology and Genetics
Bilkent University, Ankara, TURKEY.
1998 – 2003 BSc. in Molecular Biology and Genetics
Bogazici University, Istanbul, TURKEY.
PUBLICATIONS (selected)
Full list and citations: Google Scholar: Serif Senturk
• 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 8, 14370
• 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 5:e17929, 2016
• Senturk S, Shirole N, Nowak DG, Corbo V, Vaughan A, Tuveson DA, Trotman LC, Kepecs A, Stegmeier F, Sordella R. A rapid and tunable method to temporally control Cas9 expression enables identification of essential genes and interrogation of functional gene interactions in vitro and in vivo. bioRxiv http://dx.doi.org/10.1101/023366
• Nowak DG, Cho H, Herzka T, Watrud K, DeMarco DV, Wang VM, Senturk S, Fellmann C, Ding D, Beinortas T, Kleinamn D, Chen M, Sordella R, Wilkinson JE, Castillo-Martin M, Cordon-Cardo C, Robinson BD and Trotman LC. Myc drives Pten/p53-deficient proliferation and metastasis due to Il6-secretion and Akt-suppression via Phlpp2. Cancer Discovery, CD-14-1113 (Epub), 2015
• 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. PNAS, 111(32): E3287-96, 2014
• 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, 42: 1709-1715, 2013
• Buentempo F, Ersahin T, Missiroli S, Senturk S, Etro D, Ozturk M, Capitani S, Cetin-Atalay R, Neri LM. Inhibition of Akt signaling in hepatoma cells induces apoptotic cell death independent of Akt activation status. Investigational New Drugs, 29(6): 1303-13, 2011
• 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, 38(6): 4111-23, 2011
• Senturk S, Mumcuoglu M, Gursoy-Yuzugullu O, Cingoz B, Akcali KC, Ozturk M. Transforming Growth Factor-Beta Induces Senescence Arrest in Hepatocellular Carcinoma Cells and Inhibits Tumor Growth. Hepatology, 52(3): 966-74, 2010
• Mumcuoglu M, Bagislar S, Yuzugullu H, Alotaibi H, Senturk S, Telkoparan P, Gur-Dedeoglu B, Cingoz B, Bozkurt B, Tazebay U, Yulug IG, Akcali KC, Ozturk M. The ability to generate senescent progeny as a mechanism underlying breast cancer cell heterogeneity. PLoS ONE 5(6) e11288, 2010
• Yuzugullu H, Benhaj K, Ozturk N, Senturk S, Celik E, Toylu A, Tasdemir N, Yilmaz M, Erdal E, Akcali KC, Atabey N, and Ozturk M. Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells. Molecular Cancer, 8(1): 90, 2009
• Ozturk M, Arslan-Ergul A, Bagislar S, Senturk S, Yuzugullu H. Senescence and Immortality in Hepatocellular Carcinoma. Cancer Letters, 286(1): 103-113, 2009
• 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, and Ozturk M. Reprogramming of replicative senescence in hepatocellular carcinoma-derived cells. PNAS, 103: 2178-2183, 2006
PATENTS
• Methods and Compositions for Inhibiting Growth and Epithelial to Mesenchymal Transition (EMT) in Cancer Cells. WO2015200725 A1, Application number: PCT/US2015/037830