Hôte : A. Piazza 

 

Hôte : François ROUSSET                                                      

                                            

 

Hôte : Zayna CHAKER                                                                                                                                                                                                                                 

 

Hôte : Bertrand MOLLEREAU

 

90% of all cancers are of epithelial origin. Technically, adenocarcinoma founding event occurs when a tumor cell leaves the epithelial compartment to invade neighboring tissues. This step, called epithelial basal extrusion, is mostly ignored due to its elusiveness. We have developed an in vivo model dedicated to its study in the drosophila equivalent of the prostate: the accessory gland. We have shown that tumor basal extrusion is molecularly controlled by PI3K/Akt and Ras/MAPK pathways via autocrine mechanisms, and relies also on cholesterol metabolism deregulation. Furthermore, our recent work indicates that this step could also be a major actor in resistance to treatment: by reproducing breast/prostate endocrine therapy, we show that repression of sex steroid signaling modifies basal extrusion, leading to the formation a new population of highly proliferative, resistant tumor cells. We are now searching for the molecular mechanisms that are mobilized to adapt a tumor cell to its treatment. Our current work indicates that the non-canonical Notch pathway controls the transdifferentiation of a tumor cell into a resistant tumor cell.
Thus, our work indicates that, in drosophila, basal extrusion is a highly controlled event leading to both tumor formation and tumor resistance. A better understanding of these mechanisms could open new fields of investigation to apprehend epithelial cancer progression.

 

 

Thomas LEPOUTRE (Institut Camille Jordan - Lyon)                             

 

Hôte : Caroline LEROUX & David DURANTEL

 

Due to their physiological and genetic similarities to humans, non-human primates (NHPs), such as rhesus and cynomolgus monkeys, serve as indispensable models for evaluating vaccines and therapeutics, as well as for studying the pathogenesis of human viral infections. However, not all viruses that cause human diseases replicate efficiently or manifest comparable pathologies in macaques. Therefore, understanding virus–host interactions, often referred to as the “arms race,” is critical for the rational development of primate models.
The host range of HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), is extremely narrow, with productive replication occurring only in humans and chimpanzees. For many years, the reason why HIV-1 fails to replicate in macaque cells remained unclear. About two decades ago, several host cellular factors that restrict HIV-1 replication in macaque cells were identified. Among these, tripartite motif-containing protein 5α (TRIM5α) was found to be a major anti-HIV-1 restriction factor in macaque cells. TRIM5α potently inhibits HIV-1 replication after viral entry by blocking uncoating and subsequent reverse transcription.
Subsequent studies clarified the functional domains of viral proteins that interact with these HIV-1 restriction factors and elucidated their molecular mechanisms. These insights facilitated the development of HIV-1 variants capable of replicating in macaque cells, known as macaque-tropic HIV-1. During these studies, we found that specific genetic backgrounds have a strong influence on susceptibility to macaque-tropic HIV-1. This finding has enabled the prediction of viral susceptibility, thereby contributing to the establishment of more accurate and reliable animal models.
Furthermore, our laboratory is actively utilizing animal models for other viruses, including SARS-CoV-2, hepatitis B virus, and Zika virus. In addition to human viral infections, we are also investigating viral diseases in animals.
In this seminar, I will introduce our ongoing collaborative studies on domestic cat hepatitis B virus in partnership with Dr. David Durantel (INSERM), as well as our joint research on retroviruses in sheep and goats with Dr. Jocelyn Turpin and Dr. Caroline Leroux. I will also share some of our latest findings from these projects during today’s seminar.

 

 

Hôte : Daniel BOUYER 

 

Beverly GLOVER (University of Cambridge, UK)                             

         

 

Hôte : Jacques BROCARD