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Disrupting lactate shuttling and glutamine pathway in melanoma : relevance of metabolic targeting in combination with BRAF or immune checkpoint inhibitors

ABG-87073 Sujet de Thèse
13/08/2019 < 25 K€ brut annuel
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Université Catholique de Louvain, Louvain Drug Research Institute
Brussels - Belgique
Disrupting lactate shuttling and glutamine pathway in melanoma : relevance of metabolic targeting in combination with BRAF or immune checkpoint inhibitors
  • Biologie
  • Biotechnologie
  • Santé, médecine humaine, vétérinaire
imaging tumor metabolism, melanoma, targeted therapies

Description du sujet

The BRAF oncogene has recently emerged as a critical regulator of the Warburg phenotype in melanoma, bringing to the fore the importance of metabolic reprogramming in the pathogenesis and treatment of advanced melanoma. Both lactate shuttling and glutamine dependency have been described to drive the metastatic phenotype of melanoma, and to be significant actors of response/resistance in the treatment of melanome, both in response to BRAF or immune checkpoint inhibition. The goal of the current project is to assess the relevance of targeting (i) the lactate shuttling in melanoma xenografts in the context of resistance to BRAF inhibition, and (ii) the glutamine pathway in the context of response to immunotherapy in melanoma, using in vivo state-of-the-art metabolic imaging techniques, namely dynamic monitoring of metabolic fluxes using hyperpolarized (HP) 13C-MRS (magnetic resonance spectroscopy) as well as steady-state assessment of metabolites using high-resolution 13C-MRS.

Prise de fonction :

01/10/2019

Nature du financement

Contrat doctoral

Précisions sur le financement

2 ans de financement à commencer au 1er octobre 2019, renouvelable une fois

Présentation établissement et labo d'accueil

Université Catholique de Louvain, Louvain Drug Research Institute

The Biomedical Magnetic Resonance Group is conducting pre-clinical research in the field of cancer imaging, and is more specifically studying the tumor micro-environment and tumor metabolism in vitro, and  in vivo in experimental tumor models.
The Biomedical Magnetic Resonance Group holds the NEST (nuclear and electron spin technologies) platform that includes facilities that support cutting edge activities in the field of biomedical magnetic resonance : 11.7T Bruker Biospec system equipped with cryoprobe, Hypersense Hyperpolarizer (Oxford Instruments) for 13C-metabolic studies, A 600MHZ NMR system (Bruker) for in vitro studies, and  4 EPR systems (electron paramagnetic resonance).

Intitulé du doctorat

Doctorat en Sciences Biomédicales et Pharmaceutiques

Pays d'obtention du doctorat

Belgique

Etablissement délivrant le doctorat

UCLouvain

Ecole doctorale

Sciences pharmaceutiques

Profil du candidat


The successful applicant must have the following:
•A Master degree in biomedical sciences, pharmacy, biochemistry or similar field, with a mimum average results of 70% (14/20) for the master degree.
•High motivation, curiosity, and commitment to scientific excellence
•Background in cell biology and molecular biology
•Experience in mammalian cell culture
•Knowledge on cellular signaling cascades and regulation mechanisms, immunology, tumor biology, or in vivo experimentation is an advantage
•Interest in imaging and spectroscopy
•Team player skills and enthusiasm to work in a multi-disciplinary, collaborative environment
•Excellent knowledge of the English language

Date limite de candidature

31/08/2019
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