Patrice Codogno was trained as a biochemist and cell biologist. He received his PhD at the University Pierre and Marie Curie in Paris (France) in 1984. Patrice Codogno was hired by INSERM in 1985. In 2013 he joined INEM. He is currently research director and heads his lab since 1999. In 2013 he joined INEM to merge his team with Gérard Friedlander’s team. Patrice Codogno is internationally recognized as a leader in the field of autophagy.

Gérard Friedlander was trained as a MD at the University Paris Pierre and Marie Curie and as a PhDH (University Paris-Diderot). Gérard Friedlander is Professor of Physiology at Paris-Descartes Medical School. Since 2014 he is Dean of the Paris-Descartes Medical School. He was the Director of the Research Center “Growth and Signaling” until 2013. Gérard Friedlander is internationally recognized in the field of nephrology and phosphate transport.

Focus

• To study the phosphate-dependent and phosphate-independent functions of phosphate transporters
• To study the molecular aspect of autophagy and its function in stress response
• To translate the basic knowledge into therapeutical avenues

Introduction

Phosphate (Pi) homeostasis occupies a central place in cell metabolism, proliferation, and development, and in bone mineralization. It is based on the coordinated functioning of membrane transporters (the ubiquitous PiT1 and 2, and the epithelial NPTs), of intracellular adaptor proteins, and of endocrine and paracrine modulators. Our aim is to investigate Pi homeostasis at the scale of the cell and of the whole body, in normal and pathological situations.

Autophagy is a lysosomal degradation route for cell constituents that are involved in maintaining the homeostasis of the cytoplasm. In situations of nutritional stress or other stress situations such as mechanical stress this route makes it possible to produce the nutrients required for cell metabolism or to adapt to stress by controling the cytoplasm homeostasis. Autophagy is also cytoprotective with regard to other situations involving stress. In particular, in cancer cells autophagy can be a response to both metabolic stress and to cancer treatments. At the cellular level, autophagy starts with the formation of a vacuole, the autophagosome, the formation of which depends on the presence of ATG (AuTophaGy-related) proteins. Ultimately, the autophagosome fuses with the lysosome.

Research objectives

• Aim 1: Determine at the cellular partners of PiTs and in vivo the phenotype of conditional invaldation of PiT1 (kidney, liver, liver, adipose tissues) (Gerard Friedlander)
• Aim 2: Carry out a molecular dissection of renal Pi loses and investigate the physiological role of Klotho (Dominique Prié)
• Aim 3: Membrane dynamics of autophagosomal compartment (Etienne Morel)
• Aim 4: Interplay between autophagy and the primary cilium: role in mechanical stress integration (Nicolas Dupont et Patrice Codogno)
• Aim 5: Role of autophagy in self-renewal of cancer stem cells and their targeting in breast cancer treatment (Maryam Mehrpour)

5 main publications

• Mai TT*, Hamaï A*, Hienzsch A* et al. - (2017) Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem in press
• Nascembeni et al. - (2017) Local detection of PtdIns3P at autophagosome biogenesis membrane platforms. Autophagy in press
• Forand A et al. - Disruption of the phosphate tarsporter Pit1 in hepatocytes improves glucose metabolism and insulin signaling by modulating the USP7/IRS1 interaction. Cell Rep 16, 2736-48
• Orhon I*, Dupont N* et al. - (2016) Primary cilium-dependent autophagy controls epithelial cell volume in response to fluid flow. Nat Cell Biol 18, 657-67
• Forand et al. - (2013) Blood EKLF1-driven PiT1 expression is critical for mouse erythroid maturation in vivo and in vitro

2017

2016

2015