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Laura Baranello's group

Topoisomerases, chromatin biology and cancer

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.

DNA Topoisomerases Scheme

Group Members

Laura Baranello Group leader, Assistant Professor
Donald Cameron Postdoc
Vladislav Kuzin PhD student
Rashid Mehmood Postdoc
Marta Trullols Master student
Anika Wiegard Postdoc

Research support

  • Wallenberg Foundation (Wallenberg Academy Fellow)
  • Vetenskapsrådet (Starting Grant)
  • Karolinska Institutet
  • KID grant
  • VINNOVA (VINNMER Marie Curie Incoming)
  • Cancerfonden

Collaborations

Our research is performed with a number of national and international collaborators:

Dr. Camilla Sjogren, Karolinska Institutet

Dr. David Levens, National Institutes of Health, USA

Dr. Craig Thomas, National Institutes of Health

Selected Publications

28237796

27058666

25056547

24398527

24755522