Investigations of the Alternative Lengthening of Telomeres (ALT) in Cancer Cells: Unlimited proliferation is one of several crucial hallmarks of cancer cells. In order to ensure immortalization, cancer cells need to avoid apoptosis due to aging. Therefore, the telomere shortening during every cell cycle has to be counteracted by active lengthening of the telomeres. Telomeres are repetitive DNA sequences at the ends of linear chromosomes and function as a protective cap to shelter them from degradation and ambiguous DNA-repair mechanisms. In most cancer types telomerase, a reverse transcriptase is activated which progressively extends the telomeres. However in up to 15% of all cancer types a telomerase-independent, so-called alternative lengthening of telomeres (ALT) pathway has been detected. ALT is characterized by heterogeneous telomere length, accumulation of extrachromosomal repeats (ECTRs), telomeric sister chromatid exchanges (T-SCEs) and colocalizations of promyelocytic leukemia (PML) nuclear bodies and telomeres (ALT-associated PML bodies (APBs)). A mechanism including DNA repair is assumed, but the actual mechanism still remains indistinct.
In order to investigate whether the formation of APBs is sufficient for the development of an ALT phenotype the effect of artificially induced formation of APBs on telomere length and heterogeneity will be analyzed by C-circle assay and our automated screening platform. This will eventually lead to follow-up experiments regarding the influence of telomere-associated factors and the recruitment of DNA damage response proteins.
Another focus of my PhD thesis is the Development of the TelNet database. TelNet is a manually curated database that provides a comprehensive compilation of human and yeast genes that are involved in telomere biology.
since 09/2012 PhD student on the "Investigations of the Alternative Lengthening of Telomeres in Cancer Cells." in the Research Group of PD Dr. Karsten Rippe Genome Organization & Function at the German Cancer Research Center (DKFZ) and BioQuant, Heidelberg
05/2012 Diploma in chemistry, Karlsruhe Institute of Technology
11/2011 - 05/2012 Diploma thesis "Surface functionalization of gold nanoparticles with peptoidic transporters." in the group of Prof. Dr. S. Bräse, Department of Organic Chemistry, Karlsruhe Institute of Technology
08/2009 Internship project "Material comparisons of cocaine samples by GC / FID" and optimization of a method for use as part of a SOP at the Forensic Institute at the State Criminal Investigation Department Stuttgart
10/2007 – 05/2012 Studies of Chemistry, Karlsruhe Institute of Technology
- Scholarship of the German National Academic Foundation (Studienstiftung des deutschen Volkes), 2013-2016
- Stipend of the Helmholtz International Graduate School for Cancer Research, 2012-2015
- Scholarship of the German National Academic Foundation (Studienstiftung des deutschen Volkes), 2008-2012
Publications and preprints
- Sieverling L, Chen Hong, Koser SD, Ginsbach P, Kleinheinz K, Hutter B, Braun DM, Cortes-Ciriano I, Xi R, Kabbe R, Park PJ, Eils R, Schlesner M, Rippe K, Jones DTW, Brors B & Feuerbach L (2017). Genomic footprints of activated telomere maintenance mechanisms in cancer. biorxiv 157560. doi: 10.1101/157560
- Braun DM, Chung I, Kepper N & Rippe K (2017). TelNet - a database for human and yeast genes involved in telomere maintenance. biorxiv 130153. doi: 10.1101/130153
- Deeg KI, Chung I, Poos AM, Braun DM, Korshunov A, Oswald M, Kepper, N, Bender S, Castel D, Lichter P, Grill J, Pfister SM, König R, Jones DT & Rippe K (2017). Dissecting telomere maintenance mechanisms in pediatric glioblastoma. biorxiv 129106. doi: 10.1101/129106
- Dominik K. Kölmel, Birgit Rudat, Delia M. Braun, Christin Bednarek, Ute Schepers and Stefan Bräse,Org. Biomol. Chem. 2013, 11, 3954-3962, Rhodamine F: a novel class of fluorous ponytailed dyes for bioconjugation.
DKFZ & BioQuant Center
Division of Chromatin Networks
Im Neuenheimer Feld 267-BQ24
BioQuant room 622a
Fax: +49 6221 54 51487