Over the years, Pouyssegur’s group has combined genetics and molecular biology to study the mechanisms of action of growth factors and has characterized the major signaling pathways controlling cell proliferation. His team has made a substantial contribution to the areas of cell surface glycoproteins, metabolism, intracellular pH regulation, identification of human Na/H exchangers and establish that intracellular pH and MAP kinase (ERKs) signaling are critical for cell cycle entry.
During the last 25 years the group has turned its interest to another essential growth mechanism: how do cells control their nutrient supply? This key process has led him to investigate mechanisms of hypoxia signaling, angiogenesis, nutritional stress and aberrant metabolism in tumours.
Currently Pouyssegur’s group pursues, at a fundamental level, the physiological role for key targets induced by nutritional stress and hypoxia in tumors. The focus is on tumor aberrant glucose metabolism (Warburg effect), glycolysis, autophagy, nutrient import driven by HIF, with an interest in translational research. Numerous anticancer targets disrupted by Zinc Finger Nucleases & CRISPR-Cas9 have been validated in preclinical mouse models, by this team (carbonic anhydrases CA9, CA12, CA2, bicarbonate transporters NBCs, MonoCarboxylate Transporters MCT1, MCT4, their chaperone CD147/Basigin and key amino acid transporters LAT1, ASCT2, xCT, and their chaperones CD98, CD44 …). These targets all share a common participation to the ‘Darwinian’ tumour selection and progression within the hypoxic, acidic and nutrient deprived tumour microenvironment.