CV Science

Christophe GROSSET MicroRNAs and genes in adult and pediatric liver cancer

Course and current status

Education

- 1998: PhD. Life and Health Sciences, University of Bordeaux, France.

- 2011: HDR Accreditation to supervise research, University of Bordeaux, France.

 

Professional Experience

- 1998-2000: Postdoctoral fellow. Department of Biochemistry and Molecular Biology, The Texas Houston Medical School, Houston, Texas, USA.

- 2000-2002: Postdoctoral fellow. Laboratoire de Greffe de Moelle, UMR CNRS 5540, University of Bordeaux, France.

- 2002-Today: INSERM Research Scientist, University of Bordeaux, France.

 

Scientific animation

- 2005 -2015: Head of the "microRNA and liver cancer" team (3-6 people).

- 2016-2021: Head of the miRCaDe team (12-18 people).

 

Scientific prizes

- 2014-2017: Prime d’Encadrement et de Recherche

 

Responsibilities, skills and expertise

- Domain of expertise: Liver, cancer, hepatocellular carcinoma, hepatoblastoma, post-transcriptional regulation, RNA-binding proteins, microRNA, molecular and cellular biology, pathway, biomarkers, therapy, RNA seq.

- Major Committee Assignments: 2005-2018

- Master Degree jury Member (10)

- Thesis jury member (8).

- HDR jury members (2)

- 2014-2015, Member of the Bordeaux University Academic and Research committees.

- Journal peer-reviewing: PNAS, Hepatology, Journal of Hepatology, British Journal of Cancer, Carcinogenesis, RNA, Nucleic Acids Research, Genome Biology…

- Member of HEPATOBIO, ILCA, AFEF, SIOPEL, SIOP. 

- Scientific coordinator of three 3-year multicentric projects (INCa PLBIO 2012, INCa TRANSLA 2013, FRM BIOINFO 2013) with biologists, bioinformaticians and/or clinicians.

 

Grants and contracts

INCa, TRANSLA 2013, FRM, BIOINFO 2013, INCa, PLBIO 2012, ANR 2010, ANR JC 2007, Cancéropôle Grand Sud-Ouest, La Ligue Nationale contre le Cancer, the University of Bordeaux Excellence Initiative 2014 and 2016 Post-doctoral fellowship program, charity grants, Fondation Groupama pour la Santé, Région Aquitaine.

 

Supervision and training

2005-2017: 6 post-docs (1 ongoing), 7 PhD theses (1 ongoing), 14 Pre-doctoral Diplomas, 4 Assistant Engineers (1 ongoing).

 

Patents:

1. CF Grosset et all. Use of catenin-beta 1-targeting microRNAs for treating liver cancer. European patent UNIVERSITE DE BORDEAUX-INSERM-UNIVERSITE PARIS SUD - PARIS XI n°B2059PC00; PCT/EP2016/065938; submitted on the 6th of July, 2016.
2. CF Grosset et all. Use of Glypican-3-targeting microRNAs for treating liver cancer. European patent UNIVERSITE DE BORDEAUX-INSERM n° B2058PC00; PCT/EP2016/065933; submitted on the 6th of July, 2016.

Scientific summary

My interest in post-transcriptional controls and their deregulation in tumorigenesis is long-standing (Grosset C et al, Cell 2000; Grosset C et al, JBC, 2004; Sagliocco F et al; Biochem J 2006; Laloo B et al, Mol & Cell Prot 2009; Simon D et al, Hum Mol Genet 2010; Laloo B et al, Biochem Soc Trans 2010).

Since 2006, I am heading an independent research team which is working on the post-transcriptional regulation of genes mediated by microRNAs in two primary cancers of the liver: Hepatocellular Carcinoma (HCC) in adults and Hepatoblastoma (HB) in very young children.

To facilitate the study of post-transcriptional mechanisms in various human cell types including primary cells, we developed an original functional method named FunREG (functional, integrated and quantitative method to measure post-transcriptional regulations) (Laloo B et al, Mol & Cell Prot 2009; Simon D et al, Hum Mol Genet 2010; Laloo B et al, Biochem Soc Trans 2010). This method enables (i) the quantitative measurements of post-transcriptional regulations mediated by either selected 3’UTRs, siRNA or microRNAs, and (ii) the comparison of these regulatory processes in physiologically relevant systems (e.g. cancerous versus primary cells). Applied to the study of liver cancer, FunREG reported for the first time post-transcriptional gene deregulations in HCC cells compared to normal hepatocytes (Laloo B et al, Mol Cell Prot 2009; Maurel M et al, Hepatology, 2013).

Thanks to three-year competitive grants from INCa (PLBIO 2012, TRANSLA 2013) and FRM (BIOINFO 2013), we reported that Glypican-3 and beta-catenin, two factors overexpressed in liver cancer and involved in Wnt/beta-catenin pathway activation, are strongly regulated by multiple microRNAs and the endoribonuclease IRE1-alpha in hepatic cells (Maurel M et al, Hepatology, 2013; Cartier F et al, Oncotarget 2017; Indersie E et al, Hep Comm 2017). Most of these microRNAs act as tumor suppressors and may constitute good candidate for microRNA-based therapies in liver cancer. We are currently validating new targets of the most efficient ones and improving our understanding about their tumor suppressive functions in liver.

This year, we reported a new experimental model of HB in chick embryo and highlighted the advantage of using RNA sequencing to investigate gene expression and reprogramming occurring in vivo in both actively growing tumoral cells and the hosting stroma (Indersie E et al, Oncotarget 2018).

Finally, we reported a 4-gene signature (HSD17B6, ITGA6, TOP2A and VIM ), transferable to the clinic and dividing HB in three groups named C1, C2A and C2B (Hooks KB et al, Hepatology 2018). These groups harbor specific molecular features but C2A is characterized by an increased expression of FANC genes and a specific activation of the Fanconi Anemia pathway. We further showed that bortezomib, a proteasome inhibitor, strongly impairs the proliferation and survival of HB cell lines in vitro, blocks FA pathway associated double-strand DNA repair and significantly impedes HB growth in vivo. In conclusion, HB therapeutic arsenal could include Bortezomib for the treatment of patients with the most aggressive tumors (Hooks KB et al, Hepatology 2018).