Nanomedicines for the active targeting of glioblastoma initiating cells

The University of Angers engages in active exchanges with all five continents, was among the first to develop strong links with Eastern Europe, and participates fully in European Union programmes. Furthermore, the School of Pharmacy of Angers has a strong programme of students and research exchange with the Schools of Pharmacy of Nottingham (UK) and Ho Chi Minh Ville (Vietnam). It is also the coordinator of the NanoFar and Nanofar + networks, the European joint doctorate programme in Nanomedicine.
At the Health Department of the University of Angers, the MINT research unit (UMR INSERM U1066/CNRS 6021) is a translational team specializing in the design and evaluation of carriers (micro and nanoparticles) for therapeutic and imaging purposes, in oncology, immunology and infectiologyin oncology and neurodegenerative diseases. The MINT laboratory is the coordinator of the European Research project ‘Niche’ and partner of ‘FormamP’ and ‘Trans-Int’. The MINT laboratory is deeply involved in the development of Nanomedicine and organized in 2014 the 2nd International Conference on “Translational Nanomedicine”. The aim of this scientific meeting was to bring together scientists, medical staff, pharmaceutical industry and regulatory bodies, in order to present and discuss the main barriers for the market access of Nanomedicine.

ABOUT THE PROJECT: Glioblastoma (GBM) continues to be an intractable disease due high rates of tumor recurrences although a classical therapy including surgery, radiotherapy and chemotherapy (Louis, D.N., et al., 2007, Acta Neuropathol, 114, 97-109). Glioblastoma initiating cells (GICs) are tumor subpopulations characterized by high resistance to conventional chemo- and radiotherapy, a capacity to initiate and sustain tumor growth and by an undifferentiated phenotype (Lathia, J.D. et al., 2015, Genes Dev., 29, 12031217); they are considered as the major origin of tumor relapses after therapy, and thus, could be a critical clinical target. GICs are protected from standard therapies by their intrinsic phenotype, and by their niche and location. GICs phenotype is characterized by high expression of multidrug resistance proteins, activation of anti-apoptotic signaling and by a quiescent state (Goffart, N. et al., 2013, Cancers, 5, 1049-1071). Furthermore, GICs are typically protected by the blood-brain-barrier, and even in cases when this barrier would be compromised, their preferential location at hypoxic sites far away from the capillaries imply that exposition to therapies is often negligible.
In this project, we aim to design nanomedicines integrating GIC-specific drugs and carriers capable of overcoming the biopharmaceutical barriers intrinsic to GBM therapy. The student will be expected to work on the design and the characterization of nanoparticles using DLS, TEM, SEM, AFM, XRD. Selected nanomedicines will be tested in a variety of cell models. These will include GIC migration tests and neurosphere models where the capacity to modulate the CXCL12/CXCR4 signaling pathway will be assayed. Finally, the nanomedicines will be tested in vivo for biodistribution, for efficacy and for mechanism of action using mice models.

The selected candidate must have recently received his/her Master of Science in the biomedical, pharmaceutical, biophysical, biochemical fields. He/She must have excellent scientific background, communication skills, team player abilities, strong motivation, result oriented attitude, self-organization. This position is open to all nationalities. The PhD program will be conducted in English and may include secondments in partner laboratories/research centers across Europe.

Your application should include (and be limited to) the following attachments:
– An essay that states your motivation and career goals (maximum 1500 words).
– A research statement.
– Curriculum Vitae (including publications and communications if any).
– Your Master of Science degree and/or official transcripts (in English).