HDR (Life Sciences) 2008 University of Paris-XI (Orsay), FRANCE
Molecular and functional characterization of genes involved in early embryonic development in vertebrates.
Gene expression regulation at the transcriptional, post-transcriptional, translational and post-translational levels play key roles in the total amount of proteins required for cellular activities during embryonic development and in tissue homeostasis of adult organisms. To illustrate this experimentally our research activities focus on (i) the function and molecular mechanisms of the RNA-binding protein, XSeb4R, (Souopgui et al., 2008; Bentaya et al., 2012), (ii) the molecular en functional characterization of some XSeb4R targets, including members of zinc finger protein ZIC gene family (Houtmeyers et al., 2013) using cell lines, mouse and frog as model systems, and (iii) developmental toxicity using the Frog Embryo Teratogenesis Assay Xenopus (FETAX) test. Our ultimate goal is to understand how unregulated gene expression leads to diseases and genetic malformations in human. This step is crucial to define appropriate measures and treatments.
Mechanisms underlying the process of epithelial-to-mesenchymal transition in morphogenesis and metastasis.
Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cell layers lose polarity and cell-cell contacts, and undergo a dramatic remodeling of the cytoskeleton, converting adherent epithelial cells into individual migratory cells that can evade the extracellular matrix. EMTs are vital for morphogenesis, wound healing, tissue regeneration, organ fibrosis, and conversion of early tumors into invasive malignancies. Initially appreciated by embryologists, EMT is attracting increasing attention from oncologists. In many tumor types, EMT subgroups have been found that have a poor prognosis and are particularly resistant to therapy. In fact, genes that play key roles in embryonic development are frequently found to be culprits in cancer, and conversely, oncogenic genes are regularly reported as important factors in embryogenesis. EMT is therefore at the crossroads of multiple cellular processes but the molecular mechanisms underlying its genesis and regulation are less understood. Our work aims specifically at screening and characterizing biomarkers that could regulate early embryonic patterning in Xenopus and serve as “molecular signatures” in several aspect of tumour genesis including screen, diagnostic, pronostic and therapy.
RESEARCH AND COOPERATION:
Strengthening the Onchocerciasis Elimination Program in Cameroon (PRD-CUD 2013-2018 grant).
Despite almost 25 years of disease control, onchocerciasis remains a major concern for several endemic countries. An estimated 18 million people suffer from this parasitic disease, with approximately 270 000 cases of blindness. The majority of infections occur in sub-Saharan Africa with Cameroon habouring 6-7 million infected persons. The worm O. volvulus, the causative agent of this disease, lives in the human body for up to 14 years, producing daily thousands of microfilariae which evade the body and the eyes. Microfilariae live for 12-18 months and although live nematodes appear to cause minimal inflamation, their death results in inflammation, causing different forms of skin symptoms and blindness. Ivermectin is the only effective drug but is not a macrofilaricide. Patients must therefore be treated for about 15 years continuously, with hope of no reinfection, rendering this treatment very costly. Transmitted by blackflies, which breed in rivers and streams, the prevalence of infection and disease in a community is related to the proximity to riverine breeding sites of the vector. The fertile riverine areas as well as many other river/stream-related activities are frequently abandoned for fear of the disease, thereby creating serious economic problems. We want to better understand the epidemiology of its clinical expression, to isolate and characterize new candidate genes with macrofilaricidal drug target potentials, and also design sensitive parasite diagnostic tools capable of certifying the elimination of the disease in treated areas.