Chromatin Biology, Topoisomerases and Cancer
I received my PhD from the University of Bologna, Italy. During my PhD training with Prof. Capranico, I became fascinated by the mechanism of topoisomerases in regulating the topology of DNA during transcription and replication, a truly fundamental processes in life. As a postdoctoral fellow, I joined the laboratory of Dr. Levens at the National Institutes of Health (NIH). During my postdoctoral training I developed a variety of new protocols for next generation sequencing that opened new horizons for the study of DNA topology. Specifically, I discovered a new mechanism that synchronizes the activity of topoisomerase 1 with the state of RNA polymerase. In 2016, I became Assistant Professor–Group Leader and Wallenberg Academy Fellow at the Karolinska Institute, Department of Cell and Molecular Biology, Stockholm (Sweden). My research program aims to define the still unknown mechanisms of topoisomerase regulation that sustain the proliferation of cancer cells. My long-term goal is to target the regulation of topoisomerases to halt cancer progression.
Mechanism and targeting of topoisomerase regulation
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.
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.
EMBO workshop “DNA Topology in genomic transactions” https://meetings.embo.org/event/21-dna-topology
Cell and Molecular Biology seminar series
Medical Program courses
"The healthy human" https://education.ki.se/course-syllabus/2LK000
"The epigenome: a platform for the integration of metabolic and signaling pathways in development and on the path to diseases" https://kiwas.ki.se/katalog/katalog/kurs/2414;jsessionid=a508b4a11f840c784347074883e5
"Cell cycle, cancer and anti-cancer targets" https://kiwas.ki.se/katalog/katalog/kurs/3115;jsessionid=3028485594cd40c9bb38f4515a0e
2010 - 2017 Postdoctoral Fellow with Dr. Levens, National Institutes of Health (NIH, USA)
2007 - 2010 PhD in Cellular, Molecular and Industrial Biology, with Prof. Capranico, University of Bologna (Italy)
Academic honours, awards and prizes
2021 Cancerfonden-Project Grant
2021 Vetenskapsrådet-Project Grant (MH)
2018 Cancerfonden-Project Grant
2018 KID Funding
2018 KI Fonder
2016 Wallenberg Academy Fellow in Medicine
2016 KI Faculty Funded Position as Assistant Professor
2016 Vetenskapsrådet-Starting Grant (MH)
2016 VINNOVA Marie Sklodowska-Curie Fellowship
2012 FARE (Fellows Award for Research Excellence), NIH (USA)