The research in my group is focused on how NER preserves genome stability. A plethora of endogenously produced and environmental agents continuously damage DNA. Different DNA repair processes, including nucleotide excision repair (NER), collectively remove DNA lesions, which - when not properly repaired - cause cellular malfunction or cell death and drive mutagenesis, respectively leading to aging and cancer.
We use live cell imaging, biochemical, proteomic and genomic tools and model organisms to study the molecular mechanism and regulatory pathways of the versatile NER process. Currently, we mainly study the crosstalk between NER and the chromatin structure, how chromatin remodeling affects genome stability and how the distribution of the different NER sub-pathways is regulated in different tissues.
Within a recent CRISPR-mediated screening we obtained new insights into how the two NER sub-pathways are differentially implicated in removing DNA lesions induced by different commonly used Pt-based chemotherapeutics. We recently identified a novel DNA damage signaling pathway mediated by R-loops and involving non-canonical activation of the ATM DNA damage-signaling kinase. In addition, we found that SWI/SNF-family of chromatin remodelers controls expression of repair/transcription factor TFIIH. We showed that mutations in SWI/SNF, often observed in cancer, affect DDR and genome stability and cellular responses to platinum drugs.