CV Science

Olivier Saulnier Junior Group Leader

Course and current status

Junior Group Leader
Genomics and Development of Childhood Cancers
Institut Curie, France
2023-present

Postdoctoral fellow in Cancer Genomics
Decoding cellular architecture and exploring developmental features of Medulloblastoma
Dr. Michael D. Taylor - The Hospital for Sick Children, Canada
2019-2023

PhD student in Pediatric Oncology
Deciphering the splicing landscape of Ewing sarcoma
Dr. Olivier Delattre & Dr. Martin Dutertre - INSERM U830, Institut Curie, France
2015-2018

Master student in Bioinformatics
Impact of atopy on risk of glioma: a Mendelian randomization study
Pr. Richard S. Houlston - The Institute of Cancer Research, UK
2013-2014

Apprenticeship in Molecular biology
Molecular characterization of anaplastic oligodendrogliomas
Pr. Jean-Yves Delattre & Pr. Marc Sanson & Dr. Ahmed Idbaih - Institut du Cerveau, France
2012-2013

Research intern in Biotechnology
Transcriptomic perturbation of take-all disease on wheat (Triticum aestivum)
Pr. Philippe Mora - Institut de Recherche pour le Développement, France
2011-2012

Research intern in Biotechnology
Impact of heavy metals on the bacterial diversity of soils in northern France
Dr. Anne Pando - Institut de Recherche pour le Développement, France
2010-2011

Scientific summary

Research interests

My research is focused on decoding the cellular architecture and resolving developmental origins of pediatric cancers.

During my PhD, in the lab of Olivier Delattre, I became an highly-skilled scientist in transcriptional regulation and alternative splicing processes of pediatric bone tumors. We identified a novel function for ERG transcription factors in alternative splicing. In addition, we demonstrated that this novel function is altered in Ewing sarcoma harboring ERG-fusion proteins and that this process participates in tumor plasticity.
Link of the publication in Nucleic Acids Research

On other hand, we also discovered that cancers characterized by oncogenic chimeric transcription factors drive tumor-specific transcription, processing, and translation of silent genomic regions. These results established a new mechanism of transcriptomic regulation, by aberrant transcription factors, that is very important for diagnosis and potentially for therapeutic targeting in these highly aggressive cancers.
Link of the publication in Molecular Cell and the Preview in Molecular Cell. This work led to an international patent

To pursue my long-standing interest in pediatric oncology and transcriptional regulation, I joined the lab of Dr. Michael Taylor, a world leading group in childhood brain cancer research. We have demonstrated that Group 4 medulloblastoma (MB) mutations converge on the CBFA complex. We have found that Group 4 MB is a ball of undifferentiated rhombic lip subventricular zone progenitor cells that persist after birth due to the failure of physiological differentiation pathways coordinated by the CBFA complex. The human specific expansion of the RL suggests MB is a direct consequence of our species evolution.
Link of the publication in Nature and the News & Views in Nature

Additionally, we have extensively described the cellular origins of Group 3 medulloblastoma. Using scRNAseq, we showed that apical Gr3 cells resemble PRTG+ve stem cells in four-week-old human embryonic hindbrain. Transformed PRTG+ve cells in the rhombic-lip were able to form tumors histologically similar to Gr3 MB with poor survival. We demonstrated that PRTG+ve RL-VZ stem cells grow adjacent to an immature vascular plexus composed of CD34+ve endothelial cells. This architecture is maintained in Gr3 MB suggesting a symbiotic neurovascular niche. Next, we showed that targeting PRTG+ve cells in vivo (using diphtheria toxin, mAb or CAR-T) constitute an effective therapy for Gr3 medulloblastoma. Overall, our model suggests that Gr3-MB is initiated during the first-to-second trimester of pregnancy, that Gr3 PRTG+ve stem cells form a symbiotic neurovascular niche to sustain an oncogenic ballet and our anti-PRTG CAR T cells represent an exciting therapeutic opportunity.

Link of the publication in Cell. This work led to an international patent

I'm now leading the Genomics and Development of Childhood Cancers lab at Institut Curie, working on tracing and exploiting the developmental origins of pediatric brain tumors. My lab combines computational biology and genomic approaches to understand how childhood cancers hijack mechanisms of the normal development.

Links

• Lab website: Genomics and Development of Childhood Cancers
• Google Scholar: Scholar profile
• Twitter: @OSaulnier_