Patrick Charnay

Patrick Charnay (born February 3, 1954) is a French biologist, researcher. Serving as an Emeritus research director for Inserm, he works and teaches in molecular genetics and development biology at the École normale supérieure (ENS) in Paris.

Biography

Charnay is a former student of the École Polytechnique (1973 school year). Upon graduation, he turned towards fundamental biology and embarked on a science thesis in Pierre Tiollais' laboratory at the Institut Pasteur. He devoted himself particularly to the research of the cloning and sequencing of the hepatitis B virus genome, as well as to the synthesis of the surface antigen in the bacterium. His research findings paved the way for the development of a safe and effective vaccine against the disease. Charnay was recruited by Inserm in 1980. After obtaining his PhD in 1981, he did a postdoctoral fellowship in Tom Maniatis' laboratory at Harvard University (Cambridge, USA), where he studied the molecular basis for the regulation of globin gene expression. In 1984, he joined the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany) as a group leader and focused on the study of transcription factors that played a decisive role in establishing the nervous system during development. Since 1989, he has been working in the Biology Department of the ENS, where he continues to study genes that play an important role in the development of the nervous system or its function and regulation. At ENS, Patrick Charnay was Director of an Inserm Unit (1993-2005), Director of the Biology Department (2000-2001 and 2016-2017) and Professor of Biology (2013-2018). He also taught at the École Polytechnique (1997-2010).[1]

Charnay has been a member of EMBO since 1995, of the Academia Europaea since 1998 and of the French Academy of Sciences since 2004.[2][3][4] During his career, he has participated in (or chaired) numerous scientific committees.

Scientific contributions

Charnay has spent most of his career focusing on the genetic regulatory mechanisms that control the development and function of the central and peripheral nervous system of vertebrates. Main scientific contributions:

  •    Cloning and sequencing of the hepatitis B virus genome and production of surface antigen (HBs) in the bacterium.[5][6][7]
  •    Basis for regulating the expression of human alpha- and beta-globin genes.[8][9]
  •    Discovery of a family of vertebrate genes encoding zinc finger transcription factors, one of which, Krox20, is expressed in two alternate territories of a segmented embryonic structure, the hindbrain or rhombencephalon, which forms medulla oblongata, pons, and cerebellum.[10][11]
  •    Deciphering the structural bases for discrimination between nucleotides of DNA by zinc fingers.[12]
  •    Discovery of members of the Eph family of tyrosine kinase receptors involved in the segmentation of the rhombencephalon.[13]
  •    Essential role of Krox20 in the rhombencephalon segmentation process and in particular in specifying segment identity, through the control of the expression of different Hox genes.[14][15][16]
  •    Decisive involvement of Krox20 in controlling the formation and maintenance of peripheral myelin.[17][18]
  •    Role of Krox20 in the rhythmogenic neural networks of the pons[19]
  •    Role of the Krox24/Egr-1 gene in pituitary and ovarian functions.[20]
  •    Involvement of the Krox24 gene in the development of late LTP and long-term memory consolidation.[21]
  •    Role of boundary capsule cells as a barrier between the central and peripheral nervous system and as a progenitor of neural and glial cells of the peripheral nervous system.[22][23][24]
  •    Deciphering the genetic network governing the expression of Krox20 and its involvement in the segmentation of the rhombencephalon.[25][26][27][28][29]
  •    Development of a mouse model reproducing all aspects of Neurofibromatosis type I.[30]

Awards and honours
  •    1988: Paris Prize of the French National League against Cancer.
  •    1995: Member of the European Molecular Biology Organisation (EMBO)
  •    1998: Member of Academia Europaea[31]
  •    2004: Member of the French Academy of Sciences[2]
  •    2005: Knight in the Order of Academic Palms

References
  1. "Notice biographique".
  2. "Académie des sciences".
  3. "Canalacadémie".
  4. "Industrie technologique".
  5. Charnay, P., Pourcel, C., Louise, A., Fritsch, A. and Tiollais, P., « Cloning in Escherichia coli and physical structure of hepatitis B virion DNA », Proc. Nat. Acad. Sci. USA, (1979), 76, p. 2222-2226
  6. Galibert, F., Mandart, E., Fitoussi, F., Tiollais, P. and Charnay, P., « Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli », Nature, (1979), 281, p. 646-650
  7. Charnay, P., Gervais, M., Louise, A., Galibert, F. and Tiollais, P., « Biosynthesis of hepatitis B virus surface antigen in Escherichia coli », Nature, (1980), 286, p. 893-895
  8. Charnay, P. and Maniatis, T., « Transcriptional regulation of globin gene expression in the human erythroid cell line K562 », Science, (1983), 220, p. 1281-1283
  9. Charnay, P., Treisman, R., Mellon, P., Chao, M., Axel, R. and Maniatis, T., « Differences in the regulated expression of cloned human alpha globin and beta globin genes introduced into MEL cells: the role of intragenic sequences », Cell, (1984), 38, p. 251-263
  10. Lemaire, P., Revelant, O., Bravo, R. and Charnay, P., « Two genes encoding potential transcription factors with identical DNA-binding domains are activated by growth factors in cultured cells », Proc. Natl. Acad. Sci. USA, (1988), 85, p. 4691-4695
  11. Wilkinson, D., Bhatt, S., Chavrier, P., Bravo, R. and Charnay, P., « Segment-specific expression of a zinc finger gene in the developing nervous system of the mouse », Nature, (1989), 337, p. 461-464
  12. Nardelli, J., Gibson, T.J., Vesque, C. and Charnay, P., « Base sequence discrimination by zinc-finger DNA-binding domains », Nature, (1991), 349, p. 175-178
  13. Gilardi-Hebenstreit, P., Nieto, M.A., Frain, M., Mattéi, M.-G., Chestier, A., Wilkinson, D.G. and Charnay, P., « An Eph-related protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain », Oncogene, (1992), 7, p. 2499-2506
  14. Schneider-Maunoury, S., Topilko, P., Seitanidou, T., Levi, G., Cohen-Tannoudji, M., Pournin, S., Babinet, C. and Charnay, P., « Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain », Cell, (1993), 75, p. 1199-1214
  15. Sham, M.H., Vesque, C., Nonchev, S., Marshall, H., Frain, M., Das Gupta, R., Whiting, J., Wilkinson, D., Charnay, P. and Krumlauf, R., « The zinc finger gene Krox-20 regulates Hox-B2 (Hox-2.8) during hindbrain segmentation », Cell, (1993), 72, p. 183-196
  16. Voiculescu, O., Taillebourg, E., Pujades, C., Kress, C., Buart, S., Charnay, P., and Schneider-Maunoury, S., « Vertebrate hindbrain patterning: Krox-20 couples segmentation and specification of regional identity », Development, (2001), 128, p. 4967-4978
  17. Topilko, P., Schneider-Maunoury, S., Levi, G., Baron-Van Evercooren, A., Ben Younes Chennoufi, A., Seitanidou, T., Babinet, C. and Charnay, P., « Krox-20 controls myelination in the peripheral nervous system », Nature, (1994), 371, p. 796-799
  18. Decker, L., Desmarquet, C., Taillebourg, E., Ghislain, J., Vallat J.-M. and Charnay, P., « Myelin maintenance is a dynamic process requiring constant Krox20 expression », J. Neurosci., (2006), 26, p. 9771-9779
  19. Jacquin, T., Borday, V., Schneider-Maunoury, S., Topilko, P., Ghilini, G., Karo, F., Charnay, P. and Champagnat, J.,« Reorganization of pontine rhythmogenic neural networks in Krox-20 knock-out mice », (1996), 17, p. 747-758
  20. Topilko, P., Schneider-Maunoury, S., Levi, G., Trembleau, A., Gourdji, D., Driancourt, M.A., Rao, C.V. and Charnay, P., « Multiple pituitary and ovarian defects in Krox-24 (NGFIA/Egr-1) targeted mice », Mol. Endocrinol., (1998), 12, p. 107-122.
  21. Jones, M.W., Errington, M.L., French, P., Wills, T., Fine, A., Bliss, T.V.P., Garel, S., Charnay, P., Bozon, B., Laroche, S. and Davis, S., « A requirement for the immediate early gene Zif268 in the expression of late LTP and the consolidation of long-term memories », Nature Neurosci., (2001), 4, p. 289-296
  22. Vermeren, M., Maro, G., Bron, R., McGonnell, I., Charnay, P., Topilko, P. and Cohen, J., « Neural crest boundary cap cells prevent spinal motor neuron emigration at early CNS:PNS interfaces », Neuron, (2003), 37, p. 403-415
  23. Maro, G.S., Vermeren, M., Voiculescu, O., Melton, L., Cohen, J., Charnay, P. and Topilko, P., « Neural crest boundary caps constitute a source of neuronal and glial cells of the PNS », Nature Neurosci., (2004), 7, p. 930-938
  24. Gresset, A., Coulpier, F., Gerschenfeld, G., Jourdon, A., Matesic, G., Richard, L., Vallat, J.-M., Charnay, P. and Topilko, P., « Boundary caps give rise to neurogenic stem cells and terminal glia in the skin », Stem Cell Reports, (2015), 5, p. 278-290
  25. Giudicelli, F., Taillebourg, E., Charnay, P. and Gilardi-Hebenstreit, P., « Cell autonomous and cell non-autonomous roles of Krox-20 in hindbrain patterning », Genes & Dev., (2001), 15, p. 567-580
  26. Chomette, D., Frain, M., Cereghini, S., Charnay, P. and Ghislain, J., « Krox20 hindbrain cis-regulatory landscape: interplay between multiple long-range initiation and autoregulatory elements », Development, (2006), 133, p. 1253-1262
  27. Bouchoucha, Y.X., Reingruber, J., Labalette-Peaucelle, C., Wassef, M.A., Thierion, E., Holcman , D., Gilardi-Hebenstreit, P. and Charnay, P., « Dissection of a positive feedback loop driving cell fate choices in hindbrain patterning », Mol. Syst. Biol., (2013), 9, p. 690 (DOI doi: 10.1038/msb.2013.46)
  28. Thierion, E., Le Men, J., Collombet, S., Hernandez, C., Coulpier, F., Thomas-Chollier, M., Noordermeer, D., Charnay, P. and Gilardi-Hebenstreit, P., « Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements », PLoS Genetics, (2017), 13 (DOI Doi: 10.1371/journal.pone.0170315)
  29. Torbey, P., Thierion, E., Collombet, S., de Cian, A., Desmarquet-Trin-Dinh, C., Dura, M., Concordet, J.-P ., Charnay, P. and Gilardi-Hebenstreit, P., « Cooperation, cis-interactions, versatility and evolutionary plasticity of multiple cis-acting elements underlie krox20 hindbrain regulation », PLoS Genetics, (2018), 14, e1007581
  30. Radomska, K.J., Coulpier, Gresset, A., F., Schmitt, A., Debbiche, A., Lemoine, S., Wolkenstein, P., Vallat, J.M., Charnay P. and Topilko, P., « Cellular origin, tumour progression and pathogenic mechanisms of cutaneous neurofibromas revealed by mice with Nf1 knockout in boundary cap cells », Cancer Discov., (2018), 9, p. 130-147
  31. "Academia europaea".
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