Madalena Tarsounas Ph.D.
- Cancer and Haematology
- Cell and Molecular Biology
- Sophie Badie, Scientific Officer
- Eliana Tacconi, CR-UK PhD Student
- Dr Cecilia Folio Zabala, CR-UK Postdoctoral Fellow
- Dr Pawel Zawadzki, CR-UK Postdoctoral Fellow
Former Group Members
- Burcu Yigit, currently in Dr C Terhorst's lab, Medical Center of Harvard Medical School, Boston
- Kerstin Klare, currently in Prof Andrea Musacchio's lab, Max Plank Institute, Dortmund, Germany
- Maria Thanasoula, currently in Prof Andrea Musacchio's lab, Max Planck Institute, Dortmund, Germany
- Ana Rita Carlos, currently in Miguel Soares' Lab, Gulbenkian Institute, Lisbon, Portugal
- Dr Jose Escandell Planells, currently in Miguel Ferreira's Lab, Gulbenkian Institute, Lisbon, Portugal
- Dr Natsuko Suwaki, currently at GlaxoSmithKline, London, UK
- Thanasoula M, Escandell J, and Tarsounas M (2012) ATM/ATR checkpoint activation downregulates CDC25C to prevent mitotic entry with uncapped telomeres. EMBO J , 31:3398-3410.
- Badie S, Escandell JM, Bouwman P, Carlos AR, Thanasoula M, Gallardo MM, Suram A, Jaco I, Benitez J, Herbig U, Blasco MA, Jonkers J, and Tarsounas M (2010) BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping Nat Struct Mol Biol. , 17:1461-69.
- Bouwman* P, Aly* A, Escandell* J M, Pieterse M, Bartkova J, van d e, Hiddingh S, Thanasoula M, Kulkarni A, Yang Q, Haffty B G, Tommiska J, Blomqvist C, Drapkin R, Adams D J, Nevanlinna H, Bartek J, Tarsounas* M, Ganesan* S, and Jonkers* J (2010) 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers (*equal contribution and equal corresponding author) Nat Struct Mol Biol, 17(6):688-695.
- Martinez P, Thanasoula M, Carlos A R, Gomez G, Tejera A, Schoeftner S, Dominguez O, Pisano D G, Tarsounas M, and Blasco M A (2010) Mammalian Rap1 controls telomere function and gene expression through binding to telomeric and extratelomeric sites Nat Cell Biol, 12(8):768-780.
- Tejera* A M, Stagno d´Alcontres* M, Thanasoula M, Martinez P, Liao C, Tarsounas M, and Blasco M A (2010) TPP1 is required for TERT recruitment, telomere elongation and normal skin development in mice Developmental Cell, 18(5):775-789.
|Tel||+44 (0)1865 617319|
Genome instability is a hallmark of human tumours. DNA mutations and genome rearrangements are in almost all cases responsible for the aberrant proliferation and metastatic behaviour of cancer cells. Work in Dr. Madalena Tarsounas’ laboratory aims to understand the causes of genome instability and the cellular mechanisms responding to it. This will not only enhance possibilities of cancer prevention, but also the development of treatment modalities that exploit the DNA damage tolerance of cancer cells.
Telomeres are structures at chromosome ends, consisting of repetitive DNA sequences and associated proteins. They protect chromosome ends from degradation and fusion, both of which cause genome instability similar to unrepaired DNA double-strand breaks. Telomere dysfunction is often associated with the onset of tumorigenesis. The work in Dr. Tarsounas laboratory investigates how factors involved in DNA repair by homologous recombination contribute to the establishment of protective telomeric structures and how they facilitate the successful completion of telomere replication. An important aspect of this work is understanding the DNA damage response emanating from unprotected or damaged telomeres. These studies are extended to analyse how components of the shelterin telomeric complex contribute to telomere protection and tumour suppression.
Another major line of investigation in Dr. Tarsounas laboratory is the action of homologous recombination proteins at sites of ionizing radiation-induced DNA damage. A group of five essential homologous recombination factors, the RAD51 paralogs, is currently under investigation. These form complexes with each other to promote DNA double strand break repair, however their mechanism of action is still poorly understood. Previous work in the Tarsounas laboratory has shown that a key role of at least two of the RAD51 paralogs, RAD51C and XRCC3, is to mediate the generation of a DNA damage signal at break sites, required for the appropriate cellular response to damage. The study of the role of RAD51C/XRCC3 at break sites will help our understanding how DNA damage sites are efficiently recognised, possibly by remodelling the chromatin landscape surrounding DNA breaks. This work will also investigate how the other RAD51 paralog family members function at DNA breaks, both in the early steps of initiating homologous recombination reactions, as well as during subsequent steps that complete the repair process.
Sources of Funding
- Cancer Research UK
- The Royal Society
- EMBO Young Investigator
Nov 2011 Senior Group Leader, The CR-UK/MRC Gray Institute for Radiation, Oncology and Biology, University of Oxford
Dec. 2005 Group Leader, The CR-UK/MRC Gray Institute for Radiation, Oncology and Biology, University of Oxford
1999-2005 Postdoctoral Fellow, Cancer Research UK , Clare Hall Laboratories
Awards Training and Qualifications
- 2010 EMBO Young Investigator Award
- 2010 University Research Lecturership, University of Oxford
- 2003- 2005 Post Doctoral Fellowship, Breast Cancer Campaign
- 2001- 2003 Post Doctoral Fellowship, Cancer Research UK
- 1999- 2001 Post Doctoral Fellowship, European Molecular Biology Organization (EMBO)
- 1999 Ph.D., York University, Toronto, Canada
- 1995 M.Sc., York University, Toronto, Canada