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Laura Baranello

Principal researcher

Chromatin Biology, Topoisomerases and Cancer

About me

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.   

Research description

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.

 

Conference organiser

EMBO workshop “DNA Topology in genomic transactions” https://meetings.embo.org/event/21-dna-topology

Cell and Molecular Biology seminar series

Teaching portfolio

Medical Program courses

"The healthy human" https://education.ki.se/course-syllabus/2LK000  

PhD courses

"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

Education

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)

2020                EMBO

2019                NBIS

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)