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Subject of the thesis

Identification of biomarkers for preeclampsia: Cellular, animal models, and proteomic studies

Published on 1 March 2017



Abstract
Pre-eclampsia (PE) is the most threatening pathology of human pregnancy. To date, there is no biomarker to predict its occurrence. PE development is thought to be due to a failure in the invasion of trophoblastic cells known to establish the fetomaternal circulation. Also, an overexpression in the transcriptional factor STOX1 has been reported to be associated to PE development. We recently demonstrated that EG-VEGF, an angiogenic factor secreted by the placenta is increased in PE and that EG-VEGF overexpression in gravid mice causes PE development. These results suggest that EG-VEGF, alone or in combination with other placenta-secreted proteins, can be used as a potential marker to predict the occurrence of PE. The objective of the proposed project is to characterize the role of EG-VEGF in PE. Four approaches will be used; 1) A quantitative multiplex proteomic analysis of candidates biomarker in sera (n = 150 pregnant women) collected from the recently developed clinical trial in collaboration with the Grenoble hospital. Correlations between the levels of potential biomarkers of PE, including EG-VEGF and the onset of the pathology later on during pregnancy will be realized; 2) The use of invalidated mice for EG-VEGF (EG-VEGF - / -, mice developed in the laboratory) to better characterize the role of EG-VEGF throughout pregnancy, 3) The use of trophoblastic cells that overexpress STOX1 protein to test the therapeutic effects of EG-VEGF receptor antagonists; 4) The use of STOX1 mouse model, an established PE model to test the therapeutic potential of EG-VEGF receptor antagonists.

Miscellaneous information
• Recommended Master level training.
• The favorite candidate should have a strong interest in cell and molecular biology approaches, both in vitro and in vivo. Strong motivation for clinical applications and technological developments is mandatory.
• Date requested for the start of the thesis: October 01, 2017
• Contact person (Thesis supervisor):
Nadia Alfaidy-Benharouga
Laboratoire Biologie du Cancer et de l'Infection
CEA-Grenoble
17 avenue des Martyrs
38054 Grenoble Cedex 9

More information on the team's web page.