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Anne Dejean-Assémat

Anne Dejean-Assémat (born 6 January, 1957) is a French molecular biologist working on the mechanisms leading to the development of human cancers. Professor at the Pasteur Institute and Research Director at Inserm, she heads the laboratory of Nuclear Organization and Oncogenesis[1] at the Pasteur Institute.

Anne Dejean-Assémat
Born (1957-01-06) 6 January 1957 (age 67)
Cholet, France
EducationPierre-and-Marie-Curie University
Employer(s)Pasteur Institute, INSERM
Known forHuman cancers, Molecular Biology
AwardsMember of the French Academy of Sciences, Grand Prix INSERM, Sjöberg Prize
Websitehttps://research.pasteur.fr/en/team/nuclear-organization-and-oncogenesis/

Biography

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Anne Dejean-Assémat was educated at the Pierre and Marie Curie University in Paris, graduating with a Master of Science degree in Genetics in 1980. She then earned her PhD in Pierre Tiollais' laboratory at the Pasteur Institute in 1988. During her thesis, she investigated the role of integrated hepatitis B virus sequences in the development of  hepatocellular carcinoma.[2] She was appointed head of a Pasteur Institute/Inserm laboratory in 2003. Member of EMBO, of the French Academy of Sciences and of the American Academy of Arts and Sciences, she has received the Gagna and Van Heck Prize, 2003, the Prize L'Oréal-Unesco for Women in Science, 2010, the Grand Prix Inserm, 2014 and the Sjöberg Prize, 2018.

Scientific contributions

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A cancer molecular biologist, Anne Dejean-Assémat has contributed several pioneering concepts in the areas of nuclear receptors and human cancers. She discovered that genes encoding the receptors for retinoic acid  (RAR), the active derivative of vitamin A, are mutated in liver cancer and in a rare type of leukemia and deciphered the molecular and cellular bases for the cure of this leukemia, opening up unique perspectives for new differentiation and targeted cancer therapy leads.[citation needed]


She first found such a mutation in a hepatitis B virus-associated liver tumor, demonstrating that this virus, by inserting its genome into that of the hepatic cell, can disrupt neighbouring human genes and directly trigger the development of liver cancer.[3] This discovery led Dejean-Assémat's team to clone the RARb gene and identify the first responsive element to retinoic acid.[4][5] Together with Hugues de Thé, she then discovered the PML-RARa oncoprotein as the genetic defect responsible for acute promyelocytic leukemia (APL) and elucidated its oncogenic properties.[6][7]


Dejean-Assémat's further work led to the characterization of the mechanisms underlying the cure of APL by retinoic acid  and arsenic, a treatment developed in China and that remains the most efficient oncogene-targeted therapy  described so far.[8] She showed that therapeutic doses of retinoic acid can correct the deficient molecular response in the leukemic cells.[7] She also demonstrated that a particular organelle, the PML Nuclear Body, is disrupted in these cells, and that both retinoic acid  and arsenic are able to correct this cellular defect.[9] She then showed that arsenic induces the post-translational modification of PML-RARa by the small SUMO protein as well as the degradation of the oncoprotein.[10]

Dejean-Assémat's laboratory next contributed to the emergence of the SUMO field by unveiling an as yet unanticipated function for this pathway as a major epigenetic determinant of gene expression regulation, with a key role in the repression of  innate immunity[11] and the maintenance of cell identity.[12] Her work opened up exciting new avenues in regenerative medicine and cancer treatment through pharmacological modulation of sumoylation levels.

3 articles published in Anne Dejean-Assémat's laboratory have been retracted pointing to instances of image manipulation.[13] In 2019, the Pasteur Institute, CNRS and Inserm launched a joint investigation into research misconduct. The conclusion indicates that one staff scientist of the laboratory, who left the Institut Pasteur in April 2021, had engaged in fraudulent practice.[14]

Memberships and awards

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Anne Dejean-Assémat has held several scientific advisory positions and served in the Scientific Council and as a president of the Genetics, Development and Cancer committee at  Inserm (2008–2012). She received the  Mergier-Bourdeix Prize of the French Academy of Sciences (1997), the Rosen Prize from the Medical Research Foundation (1998), the Mitjaville Prize of the National Academy of Medicine (1999), the Hamdan Award for Medical Research Excellence - Therapy in Leukemia in 2000,[15] the Gagna and Van Heck Prize (2003), the Léopold Griffuel Prize from Association de recherche en cancérologie (ARC), (2010),  the Prize L'Oréal-Unesco for Women in Science,[16] (2010), the Duquesne Prize of la Ligue Nationale Contre le Cancer, (2014), the Grand Prix Inserm[17] (2014) and the Sjöberg Prize of the Royal Swedish Academy of Science[18] (2018). She was awarded two Advanced Grants from the European Research Council  (ERC), in 2011 and 2018. She was appointed Officer in the Ordre national du Mérite, (2012) and in the ordre national de la Légion d'honneur,[19] (2016).

Anne Dejean-Assémat is a member of the European Molecular Biology Organisation (EMBO) (1995), the French Academy of Science, (2004), the Academia Europaea (2005), the European Academy of Cancer Sciences, (2011) and the American Academy of Arts and Sciences (2020).

References

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  1. ^ Institut Pasteur. "Nuclear Organization and Oncogenesis". research.pasteur.fr/. Archived from the original on 2016-10-11. Retrieved 2016-01-31.
  2. ^ Dejean-Assemat, Anne (1988-01-01). Virus de l'hepatite b et hepatocarcinome : structure et role des sequences virales integrees (thesis thesis). Paris. Archived from the original on 2018-10-08. Retrieved 2019-09-11.
  3. ^ Dejean A, Bougueleret L, Grzeschik KH, Tiollais P (1986). "Hepatitis B virus DNA integration in a sequence homologous to v-erb-A and steroid receptor genes in a hepatocellular carcinoma". Nature. 322 (6074): 70–72. Bibcode:1986Natur.322...70D. doi:10.1038/322070a0. PMID 3014347. S2CID 4355348.
  4. ^ Brand N, Petkovich M, Krust A, Chambon P, de Thé H, Marchio A, Tiollais P, Dejean A (1988). "Identification of a second human retinoic acid receptor". Nature. 332 (6167): 850–853. Bibcode:1986Natur.322...70D. doi:10.1038/322070a0. PMID 3014347. S2CID 4355348.
  5. ^ De Thé H, Del-Mar-Vivanco-Ruiz M, Tiollais P, Stunnenberg H, Dejean A (1990). "Identification of a retinoic acid responsive element in the retinoic acid receptor alpha gene". Nature. 343 (6254): 177–180. doi:10.1038/343177a0. PMID 2153268. S2CID 4314508.
  6. ^ De Thé H, Chomienne C, Lanotte M, Degos L, Dejean A (1990). "The translocation of acute promyelocytic leukemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus". Nature. 347 (6293): 558–561. doi:10.1038/347558a0. PMID 2170850. S2CID 4314933.
  7. ^ a b de Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A (1991). "The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR". Cell. 66 (4): 675–684. doi:10.1016/0092-8674(91)90113-d. PMID 1652369. S2CID 40272758.
  8. ^ Hu J, Liu YF, Wu CF, Xu F, Shen ZX, Zhu YM, Li JM, Tang W, Zhao WL, Wu W, Sun HP, Chen QS, Chen B, Zhou GB, Zelent A, Waxman S, Wang ZY, Chen SJ, Chen Z (2009). "Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia". Proc Natl Acad Sci U S A. 106 (9): 3342–7. Bibcode:2009PNAS..106.3342H. doi:10.1073/pnas.0813280106. PMC 2651325. PMID 19225113.
  9. ^ Weis K, Rambaud S, Lavau C, Jansen J, Carvalho T, Carmo-Fonseca M, Lamond A, Dejean A (1994). "Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells". Cell. 76 (2): 345–356. doi:10.1016/0092-8674(94)90341-7. PMID 8293468. S2CID 36801773.
  10. ^ Müller S, Matunis MJ, Dejean A (1998). "Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus". The EMBO Journal. 17 (1): 61–70. doi:10.1093/emboj/17.1.61. PMC 1170358. PMID 9427741.
  11. ^ Decque A, Joffre O, Magalhaes JG, Cossec JC, Blecher-Gonen R, Seeler JS, Lapaquette P, Silvin A, Joubert PE, Albert ML, Amit I, Amigorena S, Dejean A (2016). "Sumoylation coordinates the repression of inflammatory and anti-viral gene programs during innate sensing". Nat Immunol. 17 (2): 140–149. doi:10.1038/ni.3342. PMID 26657003. S2CID 12081749.
  12. ^ Cossec JC, Theurillat I, Chica C, Búa Aguín S, Gaume X, Andrieux A, Iturbide A, Jouvion G, Li H, Bossis G, Seeler JS, Torres-Padilla ME, Dejean A (November 2018). "SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States". Cell Stem Cell. 23 (5): 742–757. doi:10.1016/j.stem.2018.10.001. PMID 30401455. S2CID 205251863.
  13. ^ "Retraction".
  14. ^ "Scientific integrity communication" (PDF). Institut Pasteur.
  15. ^ "Dr. Anne Dejean - Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences - HMA". www.hmaward.org.ae. Retrieved 2023-04-05.
  16. ^ "Prix L'Oréal-Unesco". Fondation L'Oréal.
  17. ^ Anne Dejean-Assémat, is awarded the Inserm Grand Prix for 2014". Newsroom | Inserm. 2014-11-26. Retrieved 2021-08-27. https://presse.inserm.fr/en/anne-dejean-assemat-is-awarded-the-inserm-grand-prix-for-2014/17041/
  18. ^ 2018's Sjöberg Prize awarded for unique treatment that cures a once fatal cancer". The Royal Swedish Acacdemy of Science. 5 February 2018. Archived from the original on 10 July 2018. https://www.kva.se/en/pressroom/pressmeddelanden/sjobergpriset-2018 Archived 2018-07-10 at the Wayback Machine
  19. ^ "Décret du 13 juillet 2016 portant promotion et nomination" : https://www.legifrance.gouv.fr/jorf/id/JORFTEXT000032891544
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