About Hannes Lans
Hannes Lans received his PhD from the Erasmus University, Rotterdam, The Netherlands, in 2005. In 2008, he received a Veni grant from NWO with which he set up C. elegans as in vivo model organism in the lab to study the DNA damage response. Currently, he is an associate professor at the Department of Molecular Genetics, Erasmus MC. His research focuses on the mechanism and regulation of Nucleotide Excision Repair (NER). This major DNA repair pathway removes many types of helix-distorting DNA lesions from the genome and is therefore essential to protect against cancer and aging.
Using mammalian and C. elegans cell biological and genetic tools, we aim to understand the mechanisms that control NER activity. We are particularly interested in the role that chromatin organization plays in regulating access and activity of NER proteins. Furthermore, we study how NER protects against disease, for which we focus on the impact of patient-derived mutations on NER functionality and organization of the DNA damage response in vivo, in the different cell types of multicellular organisms.
For more information, email to w.lans(at)erasmusmc.nl
Field(s) of expertise
Mechanism and Regulation of Nucleotide Excision Repair
Nucleotide Excision Repair (NER) is a major DNA repair pathway that removes many divers helix-distorting lesions from DNA, such as those induced by UV-light and by several cancer therapeutics. We study how the mechanism and activity of NER is regulated within chromatin and in vivo, to understand how NER deficiency leads to disease and how this pathway can be exploited for cancer therapy. For our research, we use a range of cell biological, biochemical and genetic techniques and both mammalian cells as well as C. elegans as model systems.
More information can be found at the Lans Lab
Selected recent publications:
Sabatella M, Thijssen KL, Davó-Martínez C, Vermeulen W, Lans H (2021) Tissue-Specific DNA Repair Activity of ERCC-1/XPF-1. Cell Reports 34:108608
Ribeiro-Silva C, Sabatella M, Helfricht A, Marteijn JA, Theil AF, Vermeulen W, Lans H (2020) Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair. Nature Communications 11:4868
Sabatella M, Pines A, Slyskova J, Vermeulen W, Lans H (2020) ERCC1-XPF targeting to psoralen-DNA crosslinks depends on XPA and FANCD2. Cell Mol Life Sci 77:2005-2016
Lans H, Hoeijmakers JHJ, Vermeulen W, Marteijn JA (2019) The DNA damage response to transcription stress. Nature Reviews Mol Cell Biol 20:766-784
Ribeiro-Silva C, Vermeulen W, Lans H (2019) SWI/SNF: Complex complexes in genome stability and cancer. DNA Repair 77:87-95
Ribeiro-Silva C, Aydin ÖZ, Mesquita-Ribeiro R, Slyskova J, Helfricht A, Marteijn JA, Hoeijmakers JHJ, Lans H, Vermeulen W (2018) DNA damage sensitivity of SWI/SNF-deficient cells depends on TFIIH subunit p62/GTF2H1. Nat Commun 9:4067
Sabatella M, Theil AF, Ribeiro-Silva C, Slyskova J, Thijssen K, Voskamp C, Lans H, Vermeulen W (2018) Repair protein persistence at DNA lesions characterizes XPF defect with Cockayne syndrome features. Nucleic Acids Res 46:9563-9577
Slyskova J, Sabatella M, Ribeiro-Silva C, Stok C, Theil AF, Vermeulen W, Lans H (2018) Base and nucleotide excision repair facilitate resolution of platinum drugs-induced transcription blockage. Nucleic Acids Res 46:9537-9549
Lans H, Vermeulen W (2015) Tissue specific response to DNA damage: C. elegans as role model DNA Repair 32:141-148
Aydin OZ, Vermeulen W, Lans H (2014) ISWI chromatin remodeling complexes in the DNA damage response Cell Cycle 13:3016-3025
Aydin OZ, Marteijn JA, Ribeiro-Silva C, Rodríguez López A, Wijgers N, Smeenk G, van Attikum H, Poot RA, Vermeulen W, Lans H (2014) Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription Nucleic Acids Res. 42:8473-8485
Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH (2014) Understanding nucleotide excision repair and its roles in cancer and ageing Nature Reviews Mol Cell Biol 15:465-81
Hannes Lans teaches in the Nanobiology BSc program of Erasmus University and Delft University, where he is course manager and teacher of Genetics. He also teaches in several courses of the Molecular Medicine MSc program of Erasmus MC, of which he is faculty member.
About our research
Nucleotide Excision Repair
NER is a versatile DNA repair pathway that removes many DNA-helix distorting lesions, including those induced by UV light and several cancer drugs, and plays a central role in the UV-induced DNA damage response (DDR) of eukaryotic organisms. NER is a highly conserved multi-step process that is initiated by two DNA damage-sensing mechanisms:
(1) transcription-coupled NER (TC-NER), which recognizes lesions in the transcribed strand during
(2) global genome NER (GG-NER), which senses lesions located anywhere in the genome;
Both sub-pathways utilize the same machinery to unwind DNA, excise the damage and synthesize new DNA. NER studies provide a paradigm for understanding the impact of DNA damage on human health in relation to cancer and aging. The importance of NER in protecting against disease is illustrated by the severe cancer prone and/or developmental and progeroid symptoms observed in rare NER deficiency syndromes in humans.
We utilize both mammalian cell culture as well as C. elegans to understand how NER functions within a cell and within chromatin, to better understand how NER deficiency leads to disease. Also, we study how NER and other DNA repair pathways protects cells against cancer therapeutics like platinum drugs, to be able to increase therapy effectiveness and alleviate side effects.
For our research, we make use of many diverse genetic, cell biological and biochemical techniques, proteomics as well as confocal imaging, which we use to study the sub-nuclear spatio-temporal behavior of repair and chromatin remodeling proteins in response to damage.