2000-2004: PhD in Jean-François Arnal's group, Paul Sabatier university, France
2005-2009: Post doctoral fellow in Judy Varner's group at UCSD, California USA
2009-2010: Post doctoral fellow in Anne-Catherine Prats's group, INSERM, France
Since 2010: Research Scientist at the INSERM, France
Hypoxia is a major condition for induction of angiogenesis during tumor development, nevertheless its role in lymphangiogenesis remain unclear. We investigate the role of hypoxia in the translational regulation of lymphangiogenic growth factors VEGF-C and VEGF-D. The majority of cellular stresses such as hypoxia leads to an inhibition of mRNA translation in cell by the classical cap-dependent mechanism. However, several mRNAs are translated by an alternative mechanism mediated by internal ribosome entry sites (IRESs) located in their 5' untranslated regions.
We demonstrate a novel level of regulation of tumor lymphangiogenesis using VEGF-C and -D IRES activation induced by hypoxia.
We also found a strong induction of VEGF-C IRES in both primary tumors and draining lymph nodes in pancreatic adenocarcinoma, demonstrating the necessity to increase knowledge regarding the molecular events occuring behind the invasion of cancer in the lymphatic system.
In further investigations, our purpose is to demonstrate that the process of VEGF-C and -D IRES-dependent translation plays a pivotal role in the hypoxic response in many tumors which lymph nodes are the initial or frequent sites of metastasis, including breast, skin, and pancreatic adenocarcinoma. Then, we will elaborate strategy to isolate lymph early metastatic markers to improve patients management.