Research Groups
Sylvie Noordermeer Group

DNA damage repair, homologous recombination, BRCA1

LUMC
Kép

Our Focus

Cancer is often caused by mutations in tumour suppressor genes or oncogenes. Moreover, genomic instability is one of the hallmarks of cancer. Both genomic instability and mutations are a consequence of DNA damage inaccurately repaired, underlining the importance of cellular pathways equipped with repairing DNA damage for preventing cancer. My research is directed at studying the cellular pathways repairing DNA double-stranded breaks (DSBs), one of the most cytotoxic types of DNA damage. The cell has at least four different pathways to repair DSBs, varying in their efficiency and fidelity. Our research focusses on understanding how the cell decides which pathway to activate and how this is affecting genome stability. In addition, our lab studies the multifaceted roles of BRCA1, a gene mutated in ~5% of cancers and a key player of DSB repair. Using proteomic, genomic and dedicated cellular assays, we study the regulation and function of the different protein complexes BRCA1 is involved in. 

About Sylvie Noordermeer

My Research

Sylvie Noordermeer obtained her PhD in 2012 at the Radboud University Medical Center in Nijmegen. Her PhD research focussed on the process of ubiquitylation in acute myeloid leukemia (AML). A key finding during her PhD research was that overexpression of BRE – a protein interacting with BRCA1 –has prognostic value in AML and breast cancer. Funded by fellowships by the Canadian Terry Fox foundation and the Dutch Cancer Foundation (KWF), Sylvie continued her career as a postdoctoral fellow in the laboratory of Daniel Durocher in Toronto, Canada (2012-2016) and in the group of Haico van Attikum at the Leiden University Medical Center (2017-2018). During her postdoc, she worked on the molecular determinants of DNA double strand break repair. Key findings included the USP11-mediated regulation of homologous recombination during the cell cycle and the discovery of the Shieldin complex as an active inhibitor of resection during DNA double strand break repair.

In 2019, Sylvie started an independent research group at the Department of Human Genetics at the Leiden University Medical Center. With grants from the Dutch Research Council (NWO), the Dutch cancer foundation (KWF) and Oncode, her group studies BRCA1 protein complex formation and function during DNA double strand break repair. The primary research aims of the group are to better understand the molecular regulation of repair of DNA double stranded breaks and to improve the prediction of cancer onset and therapy response for patients carrying mutations in factors involved in DNA double strand break repair.

Awards
  • 2024: Elected to the EMBO Young Investigator Programme (EMBO YIP)
  • 2020: Research Project Grant, Dutch Cancer Society (KWF)
  • 2019: NWO Vidi Grant
  • 2019: Oncode Young Investigator Grant
  • 2019: C.J. Kok Prize, Leiden University Medical Center (LUMC), for Best Fundamental Scientist
  • 2018: LUMC Zaaijer Fund Grant, supporting female scientists applying for major research grants
  • 2014: KWF Young Investigator Fellowship, Dutch Cancer Society
  • 2012: Excellence in Radiation Research for the 21st Century Fellowship, Terry Fox Foundation and Canadian Institutes of Health Research (CIHR)
Key Publications
  • 2026 | DNA end-resection is stimulated by an interaction between BRCA1 exon 11 and TOPBP1 | Marta San Martín Alonso et al. | bioRxiv (preprint) | View publication
  • 2025 | Profiling BRCA1-BRCT interactions and their functional relevance at amino acid-resolution | Venda Mangkusaputra et al. | Nucleic Acids Research | View publication
  • 2024 | (Single-stranded DNA) gaps in understanding BRCAness | Anne Schreuder et al. | Trends in Genetics | View publication
  • 2024 | EXO1 protects BRCA1-deficient cells against toxic DNA lesions | Bert van de Kooij et al. | Molecular Cell | View publication
  • 2024 | Finding novel vulnerabilities of hypomorphic BRCA1 alleles | Anne Schreuder et al. | bioRxiv (preprint) | View publication
  • 2024 | Mechanism of BRCA1-BARD1 function in DNA end resection and DNA protection | Ilaria Ceppi et al. | Nature | View publication
  • 2019 | PARP Inhibitor Resistance: A Tug-of-War in BRCA-Mutated Cells | Sylvie M. Noordermeer et al. | Trends in Cell Biology | View publication
  • 2018 | The Shieldin complex mediates 53BP1-dependent DNA repair | Sylvie M. Noordermeer et al. | Nature | View publication
  • 2015 | A mechanism for the suppression of homologous recombination in G1 cells | A. Orthwein et al. | Nature | View publication
  • 2014 | Mitosis Inhibits DNA Double-Strand Break Repair to Guard Against Telomere Fusions | A. Orthwein et al. | Science | View publication
  • 2012 | Expression of the BRCA1 complex member BRE predicts disease free survival in breast cancer | Sylvie M. Noordermeer et al. | Breast Cancer Research and Treatment | View publication
  • 2011 | High BRE expression predicts favorable outcome in adult acute myeloid leukemia, in particular among MLL-AF9 positive patients | Sylvie M. Noordermeer et al. | Blood | View publication

Members

Sylvie Noordermeer
Group leader		Ho My Phuc Vo    
PhD student		Roos Kampen    
Technician
Simona V. Antonova    
Post Doc		Timo Wendel    
Postdoc		Venda Mangkusaputra    
PhD researcher