The aim of the laboratory is to decipher the molecular interplay of DNA repair and 3D chromatin organization, and to understand how dysregulation of 3D chromatin organization leads to genome instability and cancer. We develop and apply cutting-edge super-resolution microscopy technology for single molecule imaging in intact cell and tissue samples, with the ambition that our findings may contribute to the development of new clinical treatment strategies.
DNA repair and 3D chromatin organization need to be tightly coordinated to maintain genome stability. Accordingly, disruption of either of these processes predisposes patients to cancer. To enable development of effective anti-cancer treatments and use DNA repair and chromatin organizer proteins as successful biomarkers, it is therefore critical to conclusively determine the relationship between the DNA Damage Response and chromatin organization.
Our laboratory employs cutting-edge super-resolution imaging technologies and multi-omics to unravel how dysregulation of 3D chromatin organization leads to development and progression of cancer and developmental diseases. Our research focuses on understanding the role of chromatin topology in genome stability, the molecular characterization of tumour suppressor genes and the identification of clinical opportunities by exploiting the relationship of 3D chromatin organization and DNA repair.
Our laboratory works in a highly collaborative and interdisciplinary manner at the interface of biology, physics and medical sciences. We continuously develop and apply cutting-edge microscopy and AI-based data analysis approaches for single molecule imaging in the 3D chromatin space of cells and tissues.
We are a new group at UCPH BRIC and are looking for motivated and talented candidates from all of the above-mentioned disciplines.
The role of 3D chromatin topology in genome stability
Molecular mechanisms of SMC complexes in DNA repair
3D chromatin functions of tumour suppressor proteins
- Mitotic DNA synthesis is caused by transcription-replication conflicts in BRCA2-deficient cells. Groelly FJ, Dagg RA, Petropoulos M, Rossetti GG, Prasad B, Panagopoulos A, Paulsen T, Karamichali A, Jones SE, Ochs F, Dionellis VS, Puig Lombardi E, Miossec MJ, Lockstone H, Legube G, Blackford AN, Altmeyer M, Halazonetis TD, Tarsounas M. Mol Cell. 2022 Sep 15;82(18):3382-3397.e7. doi: 10.1016/j.molcel.2022.07.011. Epub 2022 Aug 23. PMID: 36002001
- Replication Labeling Methods for Super-Resolution Imaging of Chromosome Territories and Chromatin Domains. Miron E, Windo J, Ochs F, Schermelleh L. Methods Mol Biol. 2022;2476:111-128. doi: 10.1007/978-1-0716-2221-6_9. PMID: 35635700
- Physiological Tolerance to ssDNA Enables Strand Uncoupling during DNA Replication. Ercilla A, Benada J, Amitash S, Zonderland G, Baldi G, Somyajit K, Ochs F, Costanzo V, Lukas J, Toledo L.Cell Rep. 2020 Feb 18;30(7):2416-2429.e7. doi: 10.1016/j.celrep.2020.01.067. PMID: 32075739
- Stabilization of chromatin topology safeguards genome integrity. Ochs F, Karemore G, Miron E, Brown J, Sedlackova H, Rask MB, Lampe M, Buckle V, Schermelleh L, Lukas J, Lukas C. Nature. 2019 Oct;574(7779):571-574. doi: 10.1038/s41586-019-1659-4. Epub 2019 Oct 23. PMID: 31645724
- Redox-sensitive alteration of replisome architecture safeguards genome integrity. Somyajit K, Gupta R, Sedlackova H, Neelsen KJ, Ochs F, Rask MB, Choudhary C, Lukas J. Science. 2017 Nov 10;358(6364):797-802. doi: 10.1126/science.aao3172. PMID: 29123070
- Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks. Sotiriou SK, Kamileri I, Lugli N, Evangelou K, Da-Ré C, Huber F, Padayachy L, Tardy S, Nicati NL, Barriot S, Ochs F, Lukas C, Lukas J, Gorgoulis VG, Scapozza L, Halazonetis TD. Mol Cell. 2016 Dec 15;64(6):1127-1134. doi: 10.1016/j.molcel.2016.10.038. PMID: 27984746 Free PMC article.
- 53BP1 fosters fidelity of homology-directed DNA repair. Ochs F, Somyajit K, Altmeyer M, Rask MB, Lukas J, Lukas C. Nat Struct Mol Biol. 2016 Aug;23(8):714-21. doi: 10.1038/nsmb.3251. Epub 2016 Jun 27. PMID: 27348077
17 November 2023, on bric.ku.dk
7 June 2023, on bric.ku.dk