Molecular regulations of (lymph)angiogenic factors in vascular pathologies.
The lymphatic system plays a major role in physiology. It collects fluid, fat and immune cells and transport them back to the circulation through the subclavarian vein. In pathology, a dysfunction of the lymphatic system induces lymphedema, a debilitating condition due to the fat and fluid accumulation in the arm or in the leg. More recently, the lymphatic system has been associated to the cardiac function. It plays a role in preventing and reducing cardiac post-ischemic edema. Then, the lymphatic system is a major actor in solid tumor dissemination as it provides routes for tumor cell to metastasize. Altogether, these pathologies are associated with stressed conditions including hypoxia and increased temperature (heat shock) leading to major modification of gene expression. During stress, we observe an inhibition of the overall translation except for certain mRNAs that contain an internal ribosome entry site (IRES) in their 5’ untranslated region.
Our group is studying the molecular regulations of (lymph) angiogenic growth factors, mainly at the translational level in those pathologies. Our main objectives are to:
- Study the translational regulations of (lymph)angiogenic factors during stress: role of IRES and of their trans-acting factors (ITAFs).
- Develop multicistronic IRES-based therapeutic lentivectors for combined gene therapy of ischemic heart disease as well as other vascular pathologies such as leg ischemia and lymphedema.
- Determine the role of the lymphatic system in myocardial infarction.
- Identify molecular and metabolic mechanisms involved in lymphatic dysfunction in lymphedema.
- Study the relationship between lymphatic system and adipose tissue in cancer associated cachexia.
Expected impact on health
To identify new biomarkers and molecular targets for the improvement of diagnosis and treatment of vascular pathologies.
To develop a clinical assay of combined gene therapy of ischemic heart disease.
Cooperations / Partnerships
- Lilly pharmaceutical, New York, USA
- European network REFBIO
- Inca-GSO-Ligue- ARC-AFM
- Foundation Health Cancer Toulouse
Lymphatic, gene expression, translation, RNA, (lymp)angiogenesis, growth factors, cardiac ischemia, lymphedema, cachexia.
Dermolipectomy tissue collection from patients who develop lymphedema.
Viral vectors, animal models, primary culture of endothelial cells, fluidigm.