CV Science

Olivier Tabary PhD Biomedical engineering

Course and current status

2006 –   Now Principal investigator (CR1) Inserm, CDR St Antoine 

2005 – 2006  Postdoctoral fellow, CDR St Antoine, Paris, France.

Head of unit: Pr. Annick Clément.

2003 – 2005 Postdoctoral fellow, EMBL, Heidelberg, Germany Head of unit: Dr. Carsten Schultz.

2002 – 2003 Postdoctoral fellow, Inserm E213, Hôpital Trousseau,  Paris, France. Head of unit: Pr. Annick Clément.

1998 – 2001 PhD Stutent, Inserm U 514, Champagne-Ardenne University, Reims, France. Head of unit: Dr. Edith Puchelle.

Oct. 1997 – Mars 1998    National Serviceman, Center of Research of health army (CRRSA),  Grenoble, France. Head of unit: Dr. Françis Hérodin

Scientific summary

Background:  Impairment of the activity of the CFTR chloride channel observed in cystic fibrosis (CF) patients is the main cause of the deterioration of lung function. In 2008, the chloride channel ANO1 was identified and proposed as a potential therapeutic target to restore chloride efflux in the lung in CF. Previous works from our laboratory have shown that ANO1 activity and expression were reduced in a CF context by an unknown mechanism (Ruffin et al., 2013).

Aims: The aim of this work is to understand the origin of the reduced expression of ANO1 in CF by studying the role of miRNAs which regulate negatively gene expression.

Methods: We performed bio-informatic approaches to study miRNAs that could target ANO1 and evaluated the expression levels of miRNAs candidates by RT-qPCR in bronchial epithelial cells lines. We performed functionality experiments studying the miRNAs candidates binding to the 3'UTR of ANO1 over-expressing miRNAs, and quantifying the expression of ANO1 in these conditions. We also evaluated cells migration rate and ANO1 chloride activity modulating a miRNA which regulates ANO1.

Results: By bio-informatic studies we have identified different miRNAs as potential regulator of ANO1. We observed that one of these miRNAs is overexpressed in CF cells and a decrease of ANO1 expression and luciferase activity when we overexpress the miRNA in CF and non-CF cells. Furthermore, We observed a decrease of cells migration rate and ANO1 chloride activity when miR-9 is overexpressed.

Conclusions: Our results showed that miR-9 directly regulates ANO1 by pairing to its 3’UTR and that modulate this miRNA allows to change cells migration rate and ANO1 chloride activity. In the context of CF, it would be interesting to increase ANO1 expression and activity, so we are doing tests using “target site blocker” which are antisense oligonucleotides designed to link ANO1 3’UTR by masking miR fixation site.