Forschung

Research Profile

DNA damage is a well-recognised causal factor of gene dysfunction in cancers and age-related diseases. Exposed to reactive endogenous metabolites and environmental toxicants, DNA of all living cells continuously suffers chemical alterations. Dozens of structurally different modifications ("DNA lesions") have been identified to date; however, repair and other responses to DNA damage have been satisfactorily characterised for just a few. Our group specialises in the assessment of repair and functional consequences of structurally defined DNA lesions.

We exploit synthetic nucleotide derivatives that exactly correspond to biologically highly relevant DNA modifications induced by food carcinogens, drugs, environmental toxicants and endogenous cellular mechanisms. We have developed procedure for efficient incorporation of such synthetic DNA lesions into functional reporter gene elements. To understand the lesion-specific repair mechanisms and harmful consequences of individual lesions, we deliver these gene constructs to host cells in which defined components of DNA repair or DNA damage response pathways are impaired by pre-existing genetic defects (cells derived from patients) or have been artificially compromised (by genetic tools or inhibitors). On the long run, the knowledge of molecular and cellular mechanisms underlying the outcomes of lesion-specific responses to DNA damage shall help to characterise hazards of exposure to specific genotoxic agents and identify molecular susceptibility markers as well as potential targets for personalised therapeutic interventions (for instance, cytotoxic treatments of tumours). Current projects follow three major directions

  • Fundamental mechanisms of DNA repair - nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR)
  • Epigenetic and regulatory functions of DNA base modifications - dynamics of DNA modifications and transcriptional responses in the context of functional gene promoters.
  • DNA damage as causal factor of disease - roles of DNA adducts arising from exogenous genotoxic exposures (environment, lifestile, diet, medications) in the aetiology of human diseases associated with hereditary DNA repair defects (Xeroderma pigmentosum, Cockayne syndrome and several other neurological and degenerative diseases)

Current Projects

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Grafik: European Commission

Equipment Grant/Geräteausstattung für Forschungsvorhaben "Gezielte Erfassung von Einzelmutationen mittels Zellsortierung".

Gefördert seit 2022; Thüringer Aufbaubank Nr. 2022 FGI 0006; Zweck des Forschungsvorhabens ist die Erforschung von spezifischen Mutationen, die durch strukturell definierte DNA-Veränderungen an bestimmten Nukleotidpositionen der Reporterkonstrukte entstehen. Hierbei wird zur Anreicherung seltener Mutationen Fluoreszenz-basierte Zellsortierung angesetzt.

Research grant " Assessment of functional overlaps between human DNA repair pathways for 8-oxoguanine ". Funded since 2021; DFG project number 449772894
Abstract (DFG GEPRIS)Externer Link

Research grant "Cellular repair and toxicity determinants of the major oxidative DNA lesion thymine glycol". Funded since 2019; DFG project number 406568501
Abstract (DFG GEPRIS)Externer Link

Research grant "Effect of position and clustering of the oxidative DNA base lesion 7,8-dihydro-8-oxoguanine on gene expression and repair in mammalian cells". Funded since 2010 (extended in 2013 and 2017); DFG project number 157391409
Abstract (DFG GEPRIS)Externer Link

Completed Projects

Academic exchange grant "Synthesis and analysis of repair of thymine oxidation products in DNA". Funded 2020 - 2022; DAAD Ref. No. 57547141

Completed DFG-Projects: https://gepris.dfg.de/gepris/person/157391391Externer Link

Publikationen

Hier finden Sie eine Übersicht zu den PublikationenExterner Link