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Jacques Pouysségur

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Jacques Pouysségur is a French engineer and researcher. He was born on November 10, 1943, in Toulouse, Haute-Garonne.

He is a research director emeritus of the CNRS.[1] He has conducted research at the Institute for Research on Cancer and Aging, Nice (IRCAN),[2] at the University of Nice Sophia Antipolis.[3] From 2013 to 2021, he also worked in the Department of Medical Biology, Scientific Centre of Monaco (CSM).[4] He has been the head of the Tumor Hypoxia and Metabolism Team and a visiting professor at Kyoto Medical University, Kyoto, Japan, since 2013.[5]

Training and scientific career

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Jacques Pouysségur studied biochemistry engineering from 1962 to 1966 at the Institut national des sciences appliquées de Lyon (INSA Lyon). He completed his 2-years Civil Military Service as Professor of Biochemistry from 1966 to 1968 at the Institute of Agronomy of Algiers (Algeria). He then defended his PhD thesis in 1972 in genetic regulation of E. coli in the lab of François Stoeber, (student of Jacques Monod) at INSA Lyon. He then joined the National Cancer Institute (Dr. Ira Pastan), Bethesda, USA as a postdoctoral researcher between 1974 and 1976. He then joined in 1978 as a CNRS Research Group Leader the Centre de Biochimie University Côte d'Azur, followed by CNRS Institutes (ISBDC, IRCAN)[6] since 1978 and was Director of the ISBDC Institute, Signaling, Development Biology & Cancer, Nice between 1997 and 2007.

Scientific interests and achievements

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After his training in bacterial genetics,[7] Jacques Pouysségur combined genetics and molecular biology to identify the signalling mechanisms of growth factors controlling cell proliferation. This team contributed to the fields of glycoproteins and cell adhesion,[8][9][10] metabolism,[11][12] intracellular pH regulation and molecular identification of the human Na+/H+ exchanger.[13][14] In addition, the team determined that intracellular pH and MAP kinase (ERK1/2) are essential for the activation of mTORC1 and for controlling cell entry into the cell cycle.[15][16][17][18]

Over the past 25 years, the team has turned its interest towards the mechanisms by which cells control nutrient intake. Interest in this process led the team to study the mechanisms of HIF-proline hydroxylase signalling, HIF1 stabilization under hypoxia, angiogenesis, autophagy,[19][20][21] nutritional stress and aberrant tumor metabolism.[22]

The team is pursuing, at a fundamental, translational and pre-clinical level, the physiological role of key targets induced by nutritional stress and tumor hypoxia. The focus is on the metabolism of fermented glucose (Warburg effect) or oxidative glucose in tumours, the import of amino acids under the influence of HIF or oxidative stress. Numerous anti-cancer targets inactivated by Zinc Finger Nucleases and/or CRISPR-Cas9 (carbonic anhydrases CA9, CA12, CA2, bicarbonate carriers NBC, lactate/H+ Symporters MCT1, MCT4, their chaperone CD147/basigine, key amino acid carriers : LAT1, ASCT2, xCT and their chaperones CD98, CD44...) were analyzed on tumor lines (colon, melanoma, breast, pancreas, lung).[23][24][25][26][27][28][29][30][31] These targets, often strongly expressed in aggressive cancers, contribute to "Darwinian" selection within the hypoxic, acidic, denutrient tumor microenvironment leading to metastatic spread. Some of these targets (CA9, MCT, LAT1, ASCT2, xCT), with anticancer potential, are currently under pharmacological development.

Honours and awards

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Prizes

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Source:[32]

  • Savoie Prize (LNCC); 1989,
  • Delahautemaison Nephrology Prize (FRM); 1995,
  • Rosen Oncology Prize (FRM); 1996,
  • Lounsbery Prize of the American and French Academies of Sciences; 1999,
  • Athena and Institut de France Prize; 2001,[33]
  • Leopold Griffuel Cancer Prize (ARC); 2001,
  • Sir Hans Krebs Medal (FEBS); 2002,
  • Carl Cori Reading Award (Roswell Park, US); 2008,

Appointments

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Publications, conferences and citations

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440 articles published in peer-reviewed journals;[39] 515 scientific conferences as guest speaker - Google Scholar citations: 63,091 - h-factor: 137.[40]

References

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  1. ^ "CNRS". Archived from the original on 2019-02-21. Retrieved 2019-07-29.
  2. ^ "IRCAN". Archived from the original on 2019-02-28. Retrieved 2019-07-29.
  3. ^ "Centre Antoine Lacassagne".
  4. ^ "Centre scientifique de Monaco".
  5. ^ "Université de Kyoto" (in Japanese).
  6. ^ "Profil de recherche".
  7. ^ Pouyssegur, J; Stoeber, F (February 1974). "Genetic Control of the 2-Keto-3-Deoxy-d-Gluconate Metabolism in Escherichia coli K-12: kdg Regulon". Journal of Bacteriology. 117 (2): 641–51. doi:10.1128/JB.117.2.641-651.1974. PMC 285555. PMID 4359651.
  8. ^ Pouysségur J, et al., « Role of cell surface carbohydrates and proteins in cell behavior: studies on the biochemical reversion of an N-acetylglucosamine-deficient fibroblast mutant », Proc Natl Acad Sci., (1977) 74, p. 243-7
  9. ^ Pouysségur J. et al., « Induction of two transformation-sensitive membrane polypeptides in normal fibroblasts by a block in glycoprotein synthesis or glucose deprivation », Cell, (1977) aug;11, p. 941-7
  10. ^ Anderson WB, et al., « Adenylate cyclase in a fibroblast mutant defective in glycolipid and glycoprotein synthesis », Nature, (1978) 275, p. 223-4
  11. ^ Pouysségur J, et al., « Isolation of a Chinese hamster fibroblast mutant defective in hexose transport and aerobic glycolysis: its use to dissect the malignant phenotype », Proc Natl Acad Sci., (1980) may;77, p. 2698-701
  12. ^ Pouysségur J et al., « Relationship between increased aerobic glycolysis and DNA synthesis initiation studied using glycolytic mutant fibroblasts », Nature, (1980) 287, p. 445-7
  13. ^ Pouysségur J et al., « A specific mutation abolishing Na+/H+ antiport activity in hamster fibroblasts precludes growth at neutral and acidic pH », Proc Natl Acad Sci, (1984) 81, p. 4833-7
  14. ^ Sardet C, et al., « Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter », Cell, (1989) 56, p. 271-80
  15. ^ Pouysségur J et al., « Growth factor activation of an amiloride-sensitive Na+/H+ exchange system in quiescent fibroblasts: coupling to ribosomal protein S6 phosphorylation. », Proc Natl Acad Sci, (1982) 79, p. 3935-9
  16. ^ Pagès G, et al., « Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation », Proc Natl Acad Sci., (1993) 90, p. 8319-23
  17. ^ Lavoie JN, et al., « Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway », J Biol Chem., (1996) 271, p. 20608-16
  18. ^ Brunet A., et al., « Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry », EMBO J., (1999) 18, p. 664-74
  19. ^ Berra E., et al., « HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia », EMBO J, (2003) 22, p. 4082-90
  20. ^ Berra E, et al., « The hypoxia-inducible-factor hydroxylases bring fresh air into hypoxia signalling », EMBO Rep, (2006) 7, p. 41-5. Review
  21. ^ Pouysségur et al., « Hypoxia signalling in cancer and approaches to enforce tumour regression », Nature, (2006) 441, p. 437-43
  22. ^ Kroemer G., et al., « Tumor cell metabolism: cancer's Achilles'  », Cancer Cell., (2008) 13, p. 472-82. Review
  23. ^ Chiche J., et al., « Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. », Cancer Res., (2009) 69, p. 358-68
  24. ^ Mazure NM, et al., « Hypoxia-induced autophagy: cell death or cell survival? », Curr Opin Cell Biol., (2010) 22, p. 177-80
  25. ^ Le Floch R., et al., « CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors », Proc Natl Acad Sci, (2011) 108, p. 16663-8
  26. ^ Parks SK, et al., « Disrupting proton dynamics and energy metabolism for cancer therapy », Nature Rev Cancer., (2013) 13, p. 611-23 Review
  27. ^ Marchiq I., et al., « Genetic disruption of lactate/H+ symporters (MCTs) and their subunit CD147/BASIGIN sensitizes glycolytic tumor cells to phenformin », Cancer Res, (2015) 75, p. 171-80
  28. ^ Cormerais Y., et al., « Genetic Disruption of the Multifunctional CD98/LAT1 Complex Demonstrates the Key Role of Essential Amino Acid Transport in the Control of mTORC1 and Tumor Growth. », Cancer Res, (2016) 76, p. 4481-92
  29. ^ Ždralević M., et al., « Double genetic disruption of lactate dehydrogenases A and B is required to ablate the "Warburg effect" restricting tumor growth to oxidative metabolism », J Biol Chem., (2018) 293, p. 15947-15961
  30. ^ Dayer B., et al., « Genetic ablation of the cystine transporter xCT in pancreatic cancer cells inhibits mTORC1, survival and tumor formation: implications for potentiating chemosensitivity by erastin », Cancer Res, (2019) 79, p. 3877-3890
  31. ^ Parks SK., et al., « Lactate and Acidity in the Cancer Microenvironment», Annual Review of Cancer Biology,(2020) 4, p. 141-158
  32. ^ a b "Academia europaea".
  33. ^ "Prix Athena".
  34. ^ "INCa 1".
  35. ^ "INCa 2". 27 November 2007.
  36. ^ "Académie des sciences".
  37. ^ "Canal Académie". 22 June 2008.
  38. ^ "Nomination à l'ordre national du mérite".
  39. ^ "Publications".
  40. ^ "Google Scholar".
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