Marianne Farnebo's Group
Our mission – understanding and combating cancer through RNA
The integrity of DNA is constantly threatened by numerous intrinsic and environmental sources of damage, which must be repaired accurately to maintain normal cellular functions and prevent diseases, such as cancer and neurodegeneration. Our laboratory is investigating how cells repair their DNA and what factors that contribute to this essential process. We are in particular interested in the function and regulation of non-coding RNA in connection with DNA repair, which may pave the way for novel anti-cancer therapies based on restoring or blocking specific RNAs.
How do we reach our goal?
To build a strong and creative research team, our laboratory brings together talented people from universities around the world. We combine recent techniques with our local deep knowledge in cell biology and in close collaboration with oncologists and pathologists we create the best possible team for every research task. Together we play part in developing our next breakthrough ideas.
Exploring the involvement of RNA and associated proteins in DNA repair and genome stability
Large-scale screens and whole-genome sequencing have provided a wealth of information concerning the factors and cellular processes that contributes to the maintenance of genomic integrity and thereby help prevent human diseases. Such investigations have led to the surprising identification of RNA-binding proteins, as well as RNA itself, as regulators of DNA repair and revealed that these factors are often mutated in disorders associated with genomic instability, such as cancer. Our research focus lies on uncovering the underlying mechanism(s) of non-coding RNA and associated proteins in the repair of DNA double-strand breaks. This could open new avenues for RNA-based approaches for the treatment of cancer.
Targeting non-coding RNAs as a novel method to control DNA repair and treatment response
We are also extending our findings to the cells of patients and murine models, providing more comprehensive understanding of RNA-coupled DNA repair in vivo and the potential role of these functions in protection against tumor growth. Our goal is to open new therapeutic possibilities based on RNA.
The research in our laboratory is/was funded/supported by:
- Center for innovative medicin (CIMED)
- The Swedish Cancer Society (Cancerfonden)
- The Swedish Research Council (Vetenskapsrådet)
- The Strategic Research Program in Cancer (StratCan)
- The Cancer Society of Stockholm (Cancerföreningen)
- Karolinska Institute's Breast Cancer Theme Center (BRECT)
- Karolinska Institutet
- Swedish Society for Medical Research (SSMF)
- Hagelen Foundation
- Wenner-Gren Foundation
Control of protein synthesis through mRNA pseudouridylation by dyskerin.
Pederiva C, Trevisan DM, Peirasmaki D, Chen S, Savage SA, Larsson O, Ule J, Baranello L, Agostini F, Farnebo M
Sci Adv 2023 Jul;9(30):eadg1805
Small Cajal body-associated RNA 2 (scaRNA2) regulates DNA repair pathway choice by inhibiting DNA-PK.
Bergstrand S, O'Brien EM, Coucoravas C, Hrossova D, Peirasmaki D, Schmidli S, Dhanjal S, Pederiva C, Siggens L, Mortusewicz O, O'Rourke JJ, Farnebo M
Nat Commun 2022 Feb;13(1):1015
Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome.
Bergstrand S, Böhm S, Malmgren H, Norberg A, Sundin M, Nordgren A, Farnebo M
Cell Death Dis 2020 04;11(4):238
Neutralization of the Positive Charges on Histone Tails by RNA Promotes an Open Chromatin Structure.
Dueva R, Akopyan K, Pederiva C, Trevisan D, Dhanjal S, Lindqvist A, Farnebo M
Cell Chem Biol 2019 Oct;26(10):1436-1449.e5
Phosphorylation of the Cajal body protein WRAP53β by ATM promotes its involvement in the DNA damage response.
Coucoravas C, Dhanjal S, Henriksson S, Böhm S, Farnebo M
RNA Biol 2017 06;14(6):804-813
Splicing controls the ubiquitin response during DNA double-strand break repair.
Pederiva C, Böhm S, Julner A, Farnebo M
Cell Death Differ 2016 10;23(10):1648-57