Our research
Cancer is a biologically complex disease that causes significant deaths in the human population. Pharmaceuticals that inhibit enzymes called topoisomerases are effective at killing many types of cancer cells. Unfortunately, the body’s healthy cells are also damaged by this treatment. Development of tumor-specific topoisomerase inhibitor-based therapies will require better knowledge of the mechanism of topoisomerase activity.
Topoisomerases are important cellular enzymes; they are involved in processes in which genes are copied, or when DNA is replicated prior to cell division. They unwind the DNA double helix, so that the enzymes that are going to transcribe genes or replicate DNA strands are able to do so.
Although conventionally considered to be constitutively active enzymes, recent evidence show that topoisomerases execute their function through regulatory interactions with partner proteins that modulate their activity to affect the transcriptional outcome. Understanding the mechanism of this regulation might provide a new strategy to affect topoisomerase activity in cancer cells.
Projects
Our ongoing and future investigations are based on these findings. We use a variety of approaches including biochemical assays, next-generation sequencing techniques, genome editing and drug screens to:
- Identify new proteins regulating topoisomerase 1 and topoisomerase 2 activity. Among the potential partners we focus on transcription and chromatin factors.
- Understand the molecular details of how topoisomerases are regulated by their protein partners during transcription.
- Identify drugs targeting the stimulation of topoisomerase activity in cancer cells.
Collaborations
Our research is performed with a number of national and international collaborators:
Dr. Camilla Björkegren, Karolinska Institutet
Dr. David Levens, National Institutes of Health, USA
Dr. Craig Thomas, National Institutes of Health
Dr. Mazza (San Raffaele Hospital/Italy)
Prof. Dr. Hahn (Uni Bochum/Ger)
Prof. Dr. Vindigni (Washington University/USA)
Conference organiser
EMBO workshop “DNA Topology in genomic transactions
Cell and Molecular Biology seminar series
Co-Organizer of Cell and Molecular Biology Departmental Retreat 2023