CV Science

Sarah Lambert Dr

Course and current status

EDUCATION

June 2001: PhD Molecular and Cellular Genetics, Université Versailles Saint-Quentin-en-Yvelines.

            Supervisor : Bernard Lopez

            Subject: Role of mammalian Rad51 in homologous recombination

June 2011: Habilitation à Diriger des Recherches, Université Paris-Sud XI, Orsay.

CURRENT POSITION

2020-actual       Deputy Director of the UMR3348 “Genome Integrity, RNA & Cancer »

2015-actual       Senior group leader “DNA Recombination, Replication & Genome Stability”, Institut Curie

PREVIOUS POSITIONS

2009-2015: Junior group leader, CR1-CNRS, Institut Curie-UMR3348, Orsay.

2004-2009: Research scientist CR2-CNRS, team of Pr G. Baldacci, Institut Curie-UMR2027, Orsay.

2001-2004: Post-doctoral fellow, Pr A.M. Carr, Genome Damage and Stability Center, Sussex, UK.

FELLOWSHIPS AND AWARDS

2010-2014: ANR Young investigator program

2016-2019: Label team FRM

2020-2025: Label Team Fondation Ligue

2018-2021: Awards « Prime d’encadrement doctoral et de recherche » CNRS

Scientific summary

My research aims at understanding the spatial and temporal organization of molecular circuits that prevent stressed forks from being converted into pathological DNA structures to avoid mutation inheritance to the progeny. I have worldwide recognition in the field of genome maintenance during DNA replication. During my career, I have proven my ability to develop innovative strategies to address new challenges and to establish collaborations to create synergies leading to major discoveries (32 articles in collaborations out of 60). This is evidenced by several high impact publications that have inspired many researchers in my field. I contributed to the early works establishing functional links between homologous recombination and DNA replication in mammals (EMBO J. 2000, 2001; Oncogene 2001, 2002, 2003). Using synthetic biology approaches in yeast, I was the first to demonstrate that a single dysfunctional fork is sufficient to trigger genome rearrangement (Cell 2005, Gene & Dev 2009) and a specific mutational signature (PLoS Genetics 2012), suggesting that a restarted fork is functionally distinct from a canonical fork. Using molecular assays for in depth analysis of DNA fork structure (Methods Mol Biol 2021), my team was among the first to reveal the importance of single stranded DNA gap, instead of double strand break, to engage the recombination machinery at replication fork (Mol Cell 2010, JCS 2014). I then unraveled how the homologous recombination machinery maintains fork integrity and competence through the mechanism of recombination-dependent replication (Mol Cell 2017, Nature Comm. 2017) and its connection with chromatin remodeling and assembly (PLoS Biology 2014, PLoS Genetics 2019, Life Science Alliance 2019). By taking new research avenues, I discovered that Okazaki fragments are cis-regulators of an RNA binding protein to control replication fork degradation (Mol Cell 2023). Recently, I revealed that the activity of the homologous recombination machinery is spatially segregated in the yeast nucleus by a SUMO-based mechanism and that nuclear pore complexes foster replication restart by two non-overlapping pathways, namely SUMO protease and proteasome (Nature Comm. 2020, BioRxiv 2023). The chair of excellence in biology and health is an opportunity to implement innovative and ambitious approaches to decrypt how genome maintenance during DNA replication is influenced by the nuclear organization, cell identity and environment factors.