Fanny JaulinCentres régional de lutte contre le cancer (CRLCC) - Inserm / Gustave Roussy / Université Paris-Sud
Mes recherches
I have always been fascinated by cell shape, multicellular architecture and how this relates to tissue function. I did my PhD studies in the lab of Jean-Paul Borg working on protein complexes setting–up apico-basolateral polarity in normal epithelial tissues. As a postdoctoral fellow in New York, I trained in the labs of Geri Kreitzer (Weill Medical College) and Alan Hall (MSKCC) developping 3D cell biology and microscopy-based approaches to decrypt the role of the cytoskeleton in the morphogenesis of epithelial cells.
Now, my lab investigates the morphing of neoplastic tissues and how it affects cancer metastatic spread. We believe that characterizing the oncogenic molecular signaling pathways is not sufficient to understand and target the metastatic cascade. It is essential to integrate the comprehension of tumor architecture, controlling and resulting from tumour cell behavior. Cancers harbor a great degree of heterogeneity, mostly unrepresented in experimental model systems used by the scientific community. This impedes our understanding of neoplastic processes, the identification of common pan-cancer traits and the translation of our findings to the clinic. My team developed “translational cell biology” approaches to investigate the pathological morphing of neoplastic tissue involved in cancer cell dissemination. We monitor prospective systematic unbiased cohorts of live primary cancer explants retrieved from the operating room. The observations made from weeklong imaging of these tumors generate hypothesis that are then tested using a collection of tumour avatars (mainly Patient-Derived Xenografts (PDX) and organoids) representative of tumour heterogeneity. This bidirectional workflow, “from bedside to bench” and conversely, relies on tight collaboration with clinicians. It favors immediate implementation of the findings to the benefits of the patients and identifies common traits of tumour cell organization and behaviors that could not be predicted from experimental models systems.
Mon projet ATIP-Avenir
Epithelia, functional interfaces lining the organs, are essential for body homeostasis. The molecular mechanisms driving epithelial cell morphogenesis, proliferation and migration must be coordinated to ensure epithelial function, regeneration and repair. Alteration of these signaling pathways can lead to tumorigenesis, with >85% of human cancers originating from epithelial cells. Rho family GTPases coordinate many functions in epithelial cells. Thus, we used a siRNA-based screen to investigate the role of ~100 human Rho GTPase effectors in epithelial biology.
1) We identified a new signaling pathway in epithelial cells: the transmembrane receptor plexinA1 controls cell morphogenesis and proliferation. Autocrine activation of PlexinA1 is achieved by two semaphorin ligands that independently regulate morphogenesis and cell cycle progression. The proposed research aims at identifying plexinA1 downstream effectors and characterizing their mode of action in the regulation of cell shape, cytoskeleton, cell cycle, and ploidy control.
2) Unexpectedly, inhibition of ROCK (Rho-dependent kinase) promotes invasive behavior while preserving epithelial architecture. This is reminiscent of a process called collective invasion, reported by histopathologists for more than 30 years and preponderant in many types of cancers, nevertheless under-investigated. We have developed a new in vitro assay for the qualitative and quantitative study of collective invasion. Our goal is to elucidate the signaling pathways, dependent and independent of ROCK, promoting collective invasion. We will also explore the molecular events associated with the generation of 2 distinct cell types in the cohort: leaders and followers and their mode of cooperation.
Using a combination of in vitro and in vivo approaches, We propose to investigate the mechanisms underlying epithelial homeostasis and gain insight in the deregulation associated with tumorigenesis.