Oncology
Team DDC
DNA Damage in Cancer
Often termed as a disease of the genome, cancer is the result of random acquisition of mutations that activate oncogenes and inactivate tumor suppressors. Consequently, cellular processes including cell cycle control, transcription, apoptosis and DNA repair are affected, conferring incremental growth advantages to cells and fomenting tumorigenesis. Advances in next-generation DNA sequencing have recently enabled the detailed characterization of molecular processes leading to such DNA alterations in cancer. It became immediately clear that alterations in DNA repair pathways could predispose cells to accumulating DNA damage. On the other hand, several drugs used in cancer treatment indeed target DNA repair pathways. Although this seems like a paradox in cancer treatment, it also spawns new avenues for therapeutical options through the use of synthetic lethality in cancer cells.
Our group is interested in extending the list of drugs that take advantage of the crosstalk between DNA repair genes and developing educated designs of targeted therapies for individual tumor types. We combine cancer genomics, genetic screening approaches and pre-clinical studies in order to dissect synthetic lethality mechanisms of DNA repair in human cells that can also act together with radio or chemotherapy. To this end, we perform detailed genetic and molecular characterization of DNA repair proteins based on tumor-specific somatic or germline alterations in cancer and apply CRISPR-Cas9 based genetic screens. Together, our research aims to understand the sensitivity or resistance of tumors to various treatment regimens and how inducing defects in DNA repair machinery can be used to selectively target tumors.
- Mentors
- Dr. Frank Zenke
Head Cellular Pharmacology, Translational Innovation Platform Oncology at Merck (Industry mentor) - Dr. Amir Abdollahi
Translational Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Academic mentor)
- Dr. Frank Zenke
- Publications
- Serçin Ö, Reither S, Roidos P, Ballin N, Palikyras S, Baginska A, Rein K, Llamazares M, Halavatyi A, Winter H, Muley T, Jurkowska RZ, Abdollahi A, Zenke FT, Neumann B, Mardin BR (2019):
A solid-phase transfection platform for arrayed CRISPR screens
Molecular Systems Biology 15 (12) - Drainas AP, Lambuta RA, Ivanova I, Serçin Ö, Sarropoulos I, Smith ML, Efthymiopoulos T, Raeder B, Stütz AM, Waszak SM, Mardin BR, Korbel JO (2020):
Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells
Cell Reports 31(1) - Roidos P, Sungalee S, Benfatto S, Serçin Ö, Stütz AM, Abdollahi A, Mauer J, Zenke FT, Korbel JO, Mardin BR (2020):
A scalable CRISPR/CAS9-based fluorescent reporter assay to study DNA double-strand break repair choice
Nature Communications 11, 4077 (2020) - Dejure F, Butzer J, Lindemann RK, Mardin BR (2020):
Exploiting the metabolic dependencies of the broad amino acid transporter SLC6A14
Oncotarget. 2020; 11: 4490-4503
- Serçin Ö, Reither S, Roidos P, Ballin N, Palikyras S, Baginska A, Rein K, Llamazares M, Halavatyi A, Winter H, Muley T, Jurkowska RZ, Abdollahi A, Zenke FT, Neumann B, Mardin BR (2019):
Our Team Members
Dr. Balca R. Mardin
Group Leader
- Short Bio
- 2012–2016: Postdoc with Dr. Jan O. Korbel, European Molecular Biology Laboratories (EMBL), Heidelberg, Germany
- 2013–2015: Marie Curie IEF fellowship for postdoctoral work
- 2008–2012: PhD with Prof. Elmar Schiebel (ZMBH), Ruprecht Karls University Heidelberg, Germany
- 2005–2007: Master of Science in Molecular and Cellular Biology Program, Ruprecht-Karls-University, Heidelberg, Germany
- Contact
Dr. Salvatore Benfatto
Postdoctoral Researcher
- Short Bio
- 2016-2018: Postdoc with Prof. Massimo Delledonne, Functional Genomics Lab, University of Verona, Italy
- 2014: Visiting scientist at the Biocomputing Lab of Prof. Anna Tramontano, University “Sapienza” of Rome, Italy
- 2013–2016: PhD with Prof. Giuseppe Teti, University of Messina, Italy
- 2009-2012: Master of Science in Biology, University of Messina, Italy
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Dr. Francesca R. Dejure
Postdoctoral Researcher
- Short Bio
- 2011-2017: PhD student with Prof. Dr. Martin Eilers, University of WĂĽrzburg, Germany, Research topic: Role of the transcription factor MYC as a metabolic-stress sensor in cancer
- 2011-2014: Doctoral Scholarship of the Graduate School of Life Science (GSLS), University of WĂĽrzburg, Germany
- 2008-2010: Master of Science in Medical Biotechnologies and Molecular Medicine, University of Bari, Italy
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Dr. Özdemirhan Serçin
Postdoctoral Researcher
- Short Bio
- 2012–2015: Postdoctoral research fellow in the laboratory of Prof. Dr. Cedric Blanpain, IRIBHM, Université Libre de Bruxelles, Belgium
- 2006–2011: PhD Student and research assistant in the laboratory of Prof. Dr. Aziz Sancar, Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, NC, USA
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Dr. Alexandra VĂtor
Postdoctoral Researcher
Izlem Su Akan
Research Assistant
Nadja Ballin
Research Associate
Ramya Lakshmana Iyer
Research Assistant
- Short Bio
- 2018-2020: Internship at the Division of Cancer Epigenomics.
- 2017-2020: Master of Science in Molecular Bioscience major Cancer Biology from Ruprecht-Karl’s-Universität Heidelberg.
- 2012-2016: Bachelor of Engineering in Biotechnology, M.S Ramaiah Institute of Technology, Bangalore, India.
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