Olivier Feron, Principal Investigator

Olivier Feron is honorary FRS-FNRS Research Director and Full Professor at the Faculty of Pharmacy and Biomedical Sciences and at the Faculty of Medicine of UCLouvain where he teaches pharmacology, physiology and pathology. After a PhD in Molecular Pharmacolgy, he was trained at Harvard Medical School and the Brigham and Women’s Hospital à Boston in Boston, USA first as post-doctoral fellow and then as Instructor in Medicine. Back in belgium, he established his own laboratory progressively shifting the focus of his research from cardiovascular diseases to oncology.  Cross-fertilization between these fields was instrumental in the identification by his lab of caveolae as unique signaling platforms  involved in the regulation of endothelial NO synthase activity, angiogenesis and lipoprotein metabolism. This mixed expertise was also key to demonstrate the potential of a variety of vasomodulatory compounds to improve the efficacy of chemo- and radiotherapy.

Among the most recent discoveries of O. Feron's research group are the association between cycling hypoxia and tumor progression, the role of lactate as a key actor of tumor metabolic symbiosis, the metabolic shift from glucose toward glutamine and fatty acids in response to tumor microenvironment acidosis, and the link between polyunsaturated fatty acids, lipid droplets and ferroptosis.

Olivier Feron has obtained several awards including the prix Galien en 2000, the prix Eugène De Somer in 2008, the prix Lambertine Lacroix in 2010, the prix Pfizer in 2011, the prix Tytgat in 2017 and the prix Allard-Janssen in 2021. He is also editor-in-chief of the Journal Frontiers in Pharmacology of Anti-Cancer Drugs and member of the Royal Academy of Medicine since 2009.

Publications

Representative lab publications since 2000 :

Corbet C, Bastien E, Draoui N, Doix B, Mignion L, Jordan BF, Marchand A, Vanherck JC, Chaltin P, Schakman O, Becker HM, Riant O and Feron O. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels tumor growth inhibitory and radiosensitizing effects. Nature Comm 2018.

Corbet C, Feron O. Tumor acidosis : from the passenger to the driver's seat. Nature Rev Cancer 2017, Oct;17(10):577-593.

Corbet C, Pinto A, Martherus R, Santiago de Jesus JP, Polet F, Feron O. Acidosis Drives the Reprogramming of Fatty Acid Metabolism in Cancer Cells through Changes in Mitochondrial and Histone Acetylation. Cell Metabolism 2016, Aug 9;24(2):311-23

Pinto A, Mace Y, Drouet F, Bony E, Boidot R, Draoui N, Lobysheva I, Corbet C, Polet F, Martherus R, Deraedt Q, Rodríguez  J, Lamy C, Schicke O, Delvaux D, Louis C, Kiss R, Kriegsheim AV, Dessy C, Elias B, Quetin-Leclercq J, Riant O, Feron O. ER-specific photosensitizer unravels (1)O2-driven protein oxidation and inhibition of deubiquitinases as a generic mechanism for cancer PDT. Oncogene 2016 Jul; 35(30):3976-85

Corbet C, Ragelle H, Pourcelle V, Vanvarenberg K, Marchand-Brynaert J, Préat V, Feron O.Delivery of siRNA targeting tumor metabolism using non-covalent PEGylated chitosan nanoparticles: Identification of an optimal combination of ligand structure, linker and grafting method. J Control Release. 2016 Feb 10;223:53-63

Corbet C, Draoui N, Polet F, Pinto A, Drozak X, Riant O, Feron O. The SIRT1/HIF-2α axis drives reductive glutamine metabolism under chronic acidosis and alters tumor response to therapy. Cancer Res. 2014 Oct 1;74(19):5507-19.

Draoui N, Schicke O, Seront E, Bouzin C, Sonveaux P, Riant O, Feron O. Antitumor activity of 7-aminocarboxycoumarin derivatives, a new class of potent inhibitors of lactate influx but not efflux. Mol Cancer Ther. 2014 Jun;13(6):1410-8.

Seront E, Boidot R, Bouzin C, Karroum O, Jordan BF, Gallez B, Machiels JP, Feron O. Tumour hypoxia determines the potential of combining mTOR and autophagy  inhibitors to treat mammary tumours. Br J Cancer. 2013 Nov 12;109(10):2597-606.

Seront E, Pinto A, Bouzin C, Bertrand L, Machiels JP, Feron O. PTEN deficiency is associated with reduced sensitivity to mTOR inhibitor in human bladder cancer through the unhampered feedback loop driving PI3K/Akt activation. Br J Cancer. 2013 Sep 17;109(6):1586-92.

Boidot R, Vegran F, Meulle A, Le BA, Dessy C, Sonveaux P, Lizard-Nacol S, Feron O. Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors. Cancer Res 2012;72:939-48.

Seront E, Rottey S, Sautois B, Kerger J, D'Hondt LA, Verschaeve V, Canon JL, Dopchie C, Vandenbulcke JM, Whenham N, Goeminne JC, Clausse M, Verhoeven D, Glorieux P, Branders S, Dupont P, Schoonjans J, Feron O, Machiels JP. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Ann Oncol 2012.

Defresne F, Bouzin C, Grandjean M, Dieu M, Raes M, Hatzopoulos AK, Kupatt C, Feron O. Preconditioned endothelial progenitor cells reduce formation of melanoma metastases through SPARC-driven cell-cell interactions and endocytosis. Cancer Res 2011;71:4748-57.

Vegran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-kappaB/IL-8 pathway that drives tumor angiogenesis. Cancer Res 2011;71:2550-60.

Defresne F, Bouzin C, Guilbaud C, Dieu M, Delaive E, Michiels C, Raes M, Feron O. Differential influence of anticancer treatments and angiogenesis on the seric titer of autoantibody used as tumor and metastasis biomarker. Neoplasia 2010;12:562-70.

Daneau G, Boidot R, Martinive P, Feron O. Identification of cyclooxygenase-2 as a major actor of the transcriptomic adaptation of endothelial and tumor cells to cyclic hypoxia: effect on angiogenesis and metastases. Clin Cancer Res 2010;16:410-9.

Frerart F, Lobysheva I, Gallez B, Dessy C, Feron O. Vascular caveolin deficiency supports the angiogenic effects of nitrite, a major end product of nitric oxide metabolism in tumors. Mol Cancer Res 2009;7:1056-63.

Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, Kelley MJ, Gallez B, Wahl ML, Dewhirst MW*, Feron O* Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 2008;118:3930-42.

Frerart F, Sonveaux P, Rath G, Smoos A, Meqor A, Charlier N, Jordan BF, Saliez J, Noel A, Dessy C, Gallez B, Feron O. The acidic tumor microenvironment promotes the reconversion of nitrite into nitric oxide: towards a new and safe radiosensitizing strategy. Clin Cancer Res 2008;14:2768-74.

Dewever J, Frerart F, Bouzin C, Baudelet C, Ansiaux R, Sonveaux P, Gallez B, Dessy C, Feron O. Caveolin-1 is critical for the maturation of tumor blood vessels through the regulation of both endothelial tube formation and mural cell recruitment. Am J Pathol 2007;171:1619-28.

Bouzin C, Brouet A, De VJ, Dewever J, Feron O. Effects of vascular endothelial growth factor on the lymphocyte-endothelium interactions: identification of caveolin-1 and nitric oxide as control points of endothelial cell anergy. J Immunol 2007;178:1505-11.

Martinive P, Defresne F, Bouzin C, Saliez J, Lair F, Gregoire V, Michiels C, Dessy C, Feron O. Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia: implications for anticancer therapies. Cancer Res 2006;66:11736-44.

Martinive P, De WJ, Bouzin C, Baudelet C, Sonveaux P, Gregoire V, Gallez B, Feron O. Reversal of temporal and spatial heterogeneities in tumor perfusion identifies the tumor vascular tone as a tunable variable to improve drug delivery. Mol Cancer Ther 2006;5:1620-7.

Sbaa E, Dewever J, Martinive P, Bouzin C, Frerart F, Balligand JL, Dessy C, Feron O. Caveolin plays a central role in endothelial progenitor cell mobilization and homing in SDF-1-driven postischemic vasculogenesis. Circ Res 2006;98:1219-27.

Brouet A, Dewever J, Martinive P, Havaux X, Bouzin C, Sonveaux P, Feron O. Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide. FASEB J 2005;19:602-4.

Sonveaux P, Martinive P, Dewever J, Batova Z, Daneau G, Pelat M, Ghisdal P, Gregoire V, Dessy C, Balligand JL, Feron O. Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. Circ Res 2004;95:154-61.

Kupatt C, Dessy C, Hinkel R, Raake P, Daneau G, Bouzin C, Boekstegers P, Feron O. Heat shock protein 90 transfection reduces ischemia-reperfusion-induced myocardial dysfunction via reciprocal endothelial NO synthase serine 1177 phosphorylation and threonine 495 dephosphorylation. Arterioscler Thromb Vasc Biol 2004;24:1435-41.

Sonveaux P, Dessy C, Martinive P, Havaux X, Jordan BF, Gallez B, Gregoire V, Balligand JL, Feron O. Endothelin-1 is a critical mediator of myogenic tone in tumor arterioles: implications for cancer treatment. Cancer Res 2004;64:3209-14.

Sonveaux P, Brouet A, Havaux X, Gregoire V, Dessy C, Balligand JL, Feron O. Irradiation-induced angiogenesis through the up-regulation of the nitric oxide pathway: implications for tumor radiotherapy. Cancer Res 2003;63:1012-9.

Sonveaux P, Dessy C, Brouet A, Jordan BF, Grégoire V, Gallez B, Balligand JL,  Feron O. Modulation of the tumor vasculature functionality by ionizing radiation  accounts for tumor radiosensitization and promotes gene delivery. FASEB J. 2002 Dec;16(14):1979-81.

Brouet A, Sonveaux P, Dessy C, Moniotte S, Balligand JL, Feron O. Hsp90 and caveolin are key targets for the proangiogenic nitric oxide-mediated effects of statins. Circ Res. 2001 Nov 9;89(10):866-73.

Brouet A, Sonveaux P, Dessy C, Balligand JL, Feron O. Hsp90 ensures the transition from the early Ca2+-dependent to the late phosphorylation-dependent activation of the endothelial nitric-oxide synthase in vascular endothelial growth factor-exposed endothelial cells. J Biol Chem. 2001 Aug 31;276(35):32663-9.

Dessy C, Kelly RA, Balligand JL, Feron O. Dynamin mediates caveolar sequestration of muscarinic cholinergic receptors and alteration in NO signaling. EMBO J. 2000 Aug 15;19(16):4272-80.