November 2015 Name : WILLEMS

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Accueil Internet / Members

Willems Luc, Ir, PhDTeam leader Email - +32 4 366 93 65GIGA-CancerLaboratory of Cellular and Molecular EpigeneticsPublications

Mes sites web :http://www.giga.ulg.ac.be/cme

First name : Lucas Born : in Tienen (Belgium) on october 26, 1961 Residence : 76 rue du Scadeau, B5190 St Martin, BELGIUM Tel : private: 32-(0)81-633532 lab: 32-(0)81-622157 and 32-(0)4-3662978 fax: 32-(0)81-613888 mobile: 0476-592688 e-mail luc.willems@ulg.ac.be Married to : SMEESTERS Rita Children : Marie (11-1-1988) and Estelle (8-4-1991) Studies : - Faculty of Agronomy, Gembloux (1979-1984) Engeneer (Ingénieur) in agronomy. - Faculty of Agronomy, Gembloux (1984-1988) PhD (Docteur) in agronomy. - Faculty of Agronomy, Gembloux (1988-1995) "Agrégé de l'Enseignement supérieur". Career : - Aspirant (Research Assistant) of the "Fonds National de la Recherche Scientifique" (1984-1988) - Military obligations : (1988-1989). - Chargé de Recherches (Senior Research Assistant) of the "Fonds National de la Recherche Scientifique" (1988-1991). - Chercheur qualifié (Research Associate) of the "Fonds National de la Recherche Scientifique" (1991-1995). - Maître de conférences of the "Université de Liège" (1993-1996).

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- Maître de Recherches (Senior Research Associate) of the "Fonds National de la Recherche Scientifique" (1995-1999). - Directeur de Recherches (Research Director) of the "Fonds National de la Recherche Scientifique" (1999-present) - Invited professor of the "Facultés universitaires Notre-Dame de la Paix, FUNDP, Namur-Belgium" (1998-2010) - Professor of molecular biology at Gembloux Agro Bio-Tech - University of Liège (1996-present) Field of research : - The role of viruses in cancer - Translational research in cancer Scientific distinctions : - Lauréat du "Concours des Bourses de Voyages du Ministère de la Communauté Française" 1988. - Prix de la Fondation Cancérologique Saint-Michel 1989. - Prix Léon et Henry Frédérick 1995. - Prix de la Fondation Bekales 1996. - Prix Glaxo-SmithKline 2001-2003. - Prix Pfizer 2004. - HTLV Retrovirology Award 2011. Teaching - Molecular Biology (BIOL2015-3, 3 credits, BAC3) - Applied molecular biology (BIOL2024-3, 3 credits, MASTER 1) - Genetic modifications of animal cells (CHIB0007-1, 1 credit, postgraduation level) Editorial Board and evaluation committee - President of the SVS6 genomics evaluation committee of the French Research Agency (ANR)

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- President of the Epigenetics and Cancer committee of INSERM - Member of the editorial board of "The Journal of Virology" - Member of the editorial board of "Retrovirology” - Member of the editorial board of "Journal of Cancer Sciences" - Member of the cancerology evaluation committee of the Flanders Research Fundation (FWO) until 2014 - Reviewer of the AERES (Agence d'évaluation de la recherche et de l'enseignement, France) until 2010 - Reviewer of the IARC (Associazione Italiana per la Ricerca sul Cancro) Membership to societies - International Retrovirology Association (IRVA) - American Association of Cancerology (AACR) - American Association of Microbiology (ASM) - Belgian Society for Microbiology - Belgian Society of Biochemistry and Molecular Biology - European Lung Cancer Working Group - European Organisation for Research and Treatment of Cancer (EORTC) - Member of the Royal Academy of Medicine of Belgium Supervision of PhD theses 1995 - ADAM Emmanuelle - Régulation de l'expression du virus de la leucémie bovine 1998 - GATOT Jean-Stéphane - Rôle de l'enveloppe du virus de la leucémie bovine 1999 - DEQUIEDT Franck - Rôle de l'apoptose au cours de l'infection par le virus de la leucémie bovine 2001 - TWIZERE Jean-Claude - Transformation cellulaire par les oncoprotéines virales Tax. Rôle in vivo de la phosphorylation et identification d’un partenaire protéique, la tristétraproline. 2001 - MEREZAK Charafa - Mécanismes moléculaires impliqués dans la répression de l’expression du virus de la leucémie bovine. 2001 - LEFEBVRE Laurent - Analyse fonctionnelle de la protéine G4 du virus de la leucémie bovine. 2004 - DEBACQ Christophe - Dynamique cellulaire chez les animaux infectés par les rétrovirus BLV et HTLV-1. 2004 - COLLETE Delphine - Etude du protéome de cellules tumorales associées à une infection par le virus de la leucémie bovine. 2005 - SANCHEZ ALCARAZ Maria-Teresa - Primo-infection, sélection immune et voies apoptotiques associées au virus de la leucémie bovine. 2006 - ACHACHI Amine - Impact des amino-bisphosphonates et de l'acide valproïque sur la physiologie des lymphocytes B issus de moutons infectés par le virus de la leucémie bovine. 2007 - FLORINS Arnaud - Homéostasie du comportement lymphocytaire périphérique au cours de la leucémogenèse induite par le virus de la leucémie bovine. 2007 - GILLET Nicolas - Utilisation d’inhibiteurs d’histones désacétylases dans le cadre du traitement de leucémies. 2008 - BOXUS Mathieu : Interactions des protéines Tax des virus T-lymphotropes humains avec des facteurs cellulaires: leur rôle dans le mécanisme de transformation.

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2008 - VANDERMEERS Fabian - Etude de l’activité anti-cancéreuse des inhibiteurs de désacétylases chez des patients atteints de mésothéliome pleural. 2009 - DEFOICHE Julien : Evaluation de l’état d’activation cellulaire in vivo par mesure du taux de renouvellement de l’ARN ribosomique chez les patients atteints de leucémie lymphoïde chronique. 2011 – HUBAUX Roland : Epigenetic Therapy of Lung Cancers : Anti-tumoral effect of valproate on small cell lung cancer. 2013 - COSTA Chrisostome: The role of TGFa in mesothelioma chemotherapy. 2013 - SHIVA SHANKAR TV: The role of epigenetics in angiogenesis. 2014 – DE BROGNIEZ Alix : Study of the role of N-glycosylation sites in the pathogenesis induced by bovine leukemia virus. Promoter of undergraduate theses (since 2010) Stéphanie Raulier 2010 Alexandre Carpentier 2011 Pierre-Yves Barez 2011 Thibaut Mazy 2011 Anne Lorant 2012 Grégory Lafalize 2013 Bernard Staumont 2013 Aurélie Vréven 2014 Collavino Sabrina 2014 Sarra Ait Djebbara 2014 Yasmine Ouldamer 2014 Manon Genva 2015 David De Ridder 2015 Julie Kostek 2015 Team composition Ongoing PhD theses : Pierre-Yves Barez, Alexandre Carpentier, Malik Hamaidia, Miklos Laczik, Sathya Reddy, Florent Porquet, Bernard Staumont Post-docs : Alix de Brogniez, Hélène Gazon, Nicolas Gillet, Pradeep Chauhan, Ludovic Donth, Srikanth Perike Technicians : Jean-Rocq Jacques and Nathalie Renotte Undergraduate students : Bartimée Galvan Laboratories http://www.giga.ulg.ac.be/cms/c_18569/fr/giga-cancer-laboratoires

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- Molecular and Cellular Biology lab of Gemboux Agro-Bio Tech : avenue Maréchal Juin13, 5030 Gembloux - Belgium Tel: 32-(0)-81-622157 or -2152 (JR Jacques) - Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liège (ULg) : Allée de l'Hôpital 1 (B34), 4000 Sart-Tilman Liège - Belgium Tel: 32-(0)-4-3669365 or -4925 (N. Renotte)

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Sponsors

- “Fonds National de la Recherche Scientifique” (FNRS) : 3.4582.04 (2006-2009) 89,000 euros ; 3.4531.07 (2007-2012) 120,000 euros ; FC66850 (2010-2012) 15,000 euros ; 3.4519.10 (2010-2013) : 72,800 euros ; 3.4549.10 (2010) 48,400 euros; 1.5135.11 (2011) 78,500 euros; 3.4549.12 (2012-2015) 80,000 euros; 3.4528.12 (2012-2015) 60,000 euros; J0028.13 (2013-2014) 30,000 euros; T0060.14 (2014-2018) 360,000 euros

- Télévie: 7.4523.05 (2005-2007) 40,000 euros; 7.4588.07 (2007-2009) 25,000 euros; 7.4533.06 (2006-2008) 12,000 euros; 7.4588.06 (2006-2008) 10,000 euros; 7.4587.07 (2007-2009) 30,000 euros; 7.4535.06 (2006-2008) 20.000 euros; 7.4578.08 (2008-2010) 10,000 euros; 7.4514.10 (2010-2012) : 15,000 euros ; 7.4539.11 (10,000 euros); 7.4540.11 (10,000 euros); 7.4542.11 (2011-2013) 20,000 euros; - Belgian Foundation against Cancer: 280,000 euros (2009-2012) and 70,000 euros (2011-2014); - Sixth Research Framework Programme of the European Union (project INCA LSHC-CT-2005-018704) (2006-2010): 397,499 euros - “Neoangio” excellence program (2009-2010) : 283,000 euros - “Partenariat Public Privé” PPP INCA of the “Direction générale des Technologies, de la Recherche et de l'Énergie / DG06” of the Walloon government (2009-2013) : 320,000 euros

- “Action de Recherche Concertée Glyvir” of the “Communauté française de Belgique” (2008-2013) : 377,570 euros

- “Plan Cancer” of the “Service Public Fédéral” Bordet ULB (2009-2010): 278,532 euros; UCL (2009-2010): 116,060 euros

- Centre anticancéreux 2009 (7.000 euros), 2010 (7500 euros) 2012 (7500 euros)

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- GxABT Plan stratégique SYNBIOFOR (2011-2012) : 44,000 euros ; Agriculture is life (2013-2017) 45,000 ; - ULg Fonds Spéciaux pour la Recherche (2011-2013) : 79,983 euros; 21,867 euros; 38,807 euros - UAP VII (Belspo) (2012-2016): 500,000 euros

- Belgian Foundation against Cancer (2013-2014): 200,000 euros

Invited oral presentations (as from 2007) - Keystone meeting on Viruses and Human Cancer (Big Sky Montana, USA): Mechanisms of BLV Persistence and Leukemogenesis. March 2015 - Institute of Human Virology meeting. Vaccination against deltaretroviruses: the BLV paradigm (Baltimore, USA, September 15, 2014) - Activation of transcription and stimulation of DNA replication as cancer treatments (Kyoto, Japan, March 3, 2014) - EpiNantes. Modulation of epigenetics improves cancer therapy (Nantes, France, October 15, 2013) - Global virus Network. A recombinant attenuated vaccine that efficiently and persistently protects against bovine leukemia virus in herds: implications for GVN (Moscow, Russia, September 12, 2013) - 15th International Conference on Human Retrovirology: HTLV and related retroviruses. Montreal 26-30 June 2013 - Viruses, genes and cancer: How the DNA damage response directs the fate of HTLV-1 expressing cells (Venice, Italy, October 25, 2012) - Fond Léon Fredericq: Mesothelioma (Liège, Belgium, October 11, 2012) - Académie Royale de Médecine de Belgique (Brussels, Belgium): Transformation by deltaretroviruses: mechanisms and therapies. May 2012 - 11° journée scientifique du CRI. Epigénétique et maladies inflammatoires (Institut Pasteur Paris, France). May 2012 - Advanced seminars in Cancer Biology (Karolinska Instituted, Stockholm, Sweden; 8-11-11): Inhibition of histone deacetylases and cell cycle checkpoints as anticancer strategies. - X Congresso Argentino de Virologia (Buenos Aires, Argentina, September 2011): Novel antiretroviral therapies for BLV and HTLV. - XXV Symposium of the International Association for Comparative Research on Leukemia and related diseases (University of Tokyo, Japan): Novel antiretroviral therapies for BLV and HTLV. September 2011 - Collège Belgique. Virus et leucémies : nouvelles perspectives thérapeutiques. Namur (Belgium) December 9, 2010. - Collège Belgique. La recherche translationnelle apporte de nouvelles perspectives de traitement du mésothéliome malin de la plèvre et du cancer du poumon. Brussels (Belgium), December 1, 2010. - Viruses, genes and cancer. Venise (Italy) September 29 –October 1, 2010 - HTLV European Research Network meeting. Lyon (France) May 28-30, 2010 - 24e Journées franco-belges de Pharmacochimie. Brussels, May 20, 2010

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- The XXIV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. Columbus (USA) October 14-17, 2009 - 14th International Conference on Human Retrovirology: HTLV and related retroviruses. Salvador (Brazil) July 1-6, 2009 - Infection in Cancer EU workshop. Sesimbra (Portugal) March 10-16, 2009 - Les Vingt et Unièmes Entretiens du Centre Jacques Cartier. Montreal (Canada) October 3-5, 2008 - 7th International Foamy Virus Conference. Heidelberg (Germany) July 24-26, 2008 - Infection in Cancer EU workshop. Sesimbra (Portugal) 3-7 March, 2008 - Workshop on Modeling and identification of distributed parameter systems for cell population dynamics. Leuven (Belgium) March 12-14, 2008 - Lymphocyte kinetics in health and disease. London (UK) May 19-20, 2008 - Journée Francophones de Virologie. Paris (France) March 27-28, 2008 - HTLV European Research Network meeting. Brugge (Belgium) June 1-3, 2008 (organizer) - Simpósio Internacional sobre HTLV no Brasil. Rio de Janeiro (Brazil) June 26-28, 2008 - Third European Congress of Virology. Nurnberg (Germany) September 2-5, 2007 (chairman) - Retroviral pathogenesis meeting. Vienna (Austria) September 26, 2007 - Infection in Cancer EU workshop. Sesimbra (Portugal) March 11-14, 2007 - 13th International Conference on Human Retrovirology: HTLV and related retroviruses. Hakone (Japan) May 20-26, 2007

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REVIEW ARTICLES -1. Bovine leukemia virus : a versatile agent with various pathogenic effects in various animal species. A. Burny, C. Bruck, Y. Cleuter, D. Couez, J. Deschamps, J. Ghysdael, D. Ggregoire, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle and L. Willems (1985) Rev. de l'Institut Pasteur de Lyon, 18: 75-87. -2. Oncogène et traitement du cancer. A. Burny, Y. Cleuter, D. Couez, D. Gregoire, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke et L. Willems (1985) Rev. Med. Brux., 6: 261-264. -3. Bovine leukemia virus, a distinguished member of the human T-lymphotropic virus family. A. Burny, C. Bruck, Y. Cleuter, D. Couez, J. Deschamps, J. Ghysdael, D. Gregoire, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle and L. Willems (1985) Retroviruses in human lymphoma/leukemia. M. Miwa and al. (eds). Japan Sci. Soc. Press. (Tokyo) / VNU Science Press (Utrecht), p 219-227. -4. Bovine leukemia virus, a versatile agent with various effects in various animal species. A. Burny, C. Bruck, Y. Cleuter, D. Couez, J. Deschamps, J. Ghysdael, D. Gregoire, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle and L. Willems (1985) Cancer Res. (suppl.), 45: 4578-4582. -5. Bovine leukemia virus, a distinguished member of the human T-Lymphotropic virus family. A. Burny, C. Bruck, Y. Cleuter, D. Couez, J. Deschamps, J. Ghysdael, D. Gregoire, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle and L. Willems (1985) Retroviruses and human pathology. Humana Press Clifton (New Jersey), p 203-216. -6. Bovine leukemia virus as an inducer of bovine leukemia. A. Burny, C. Cleuter, Y. Cleuter, D.Couez, D. Gregoire, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle and L. Willems (1986) Animal models of retroviruses infection and their relationship to AIDS. Lois Ann Salzman (ed). Academic Press (New York), p 107-119. -7. La leucémie bovine : système modèle de leucémogénisation par un rétrovirus. A. Burny, Y. Cleuter, C. Dandoy, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke et L. Willems (1986) An. Méd. Vét., 130: 287-294. -8. Leukemogenesis by bovine leukemia virus (BLV) and human T-cell lymphotropic viruses : facts and hypothesis. A. Burny, Y. Cleuter, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke and L. Willems (1986) Cancer letters (suppl.), 30: 34-37. -9. Use of bovine leukemia virus proviral DNA probes for the analysis of BLV-induced leukemogenesis. R. Kettmann, L. Willems, C. Bruck, D. Gegonne, A. Van Den Broeke and A. Burny (1987) Monoclonal and DNA probes in diagnosis and preventive medecine. Gallo, Della Porta and Albertini (eds). Raven Press (New York), p 219-225. -10. Leukemogenesis by bovine leukemia virus (BLV). A. Burny, Y. Cleuter, C. Dandoy, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Tartar, A. Van Den Broeke and L.

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Willems (1987) Viruses and human cancer. Gallo, Haseltine, Klein, zur Hausen. Alan R. (eds). Liss Press (New York), p 345-353. -11. Transactivation : un phénomène biologique fondamental impliqué dans la carcinogenèse. A. Burny, Y. Cleuter, R. Kettmann, M. Mammerickx, A. Van Den Broeke, L. Willems et R. Thomas (1987) Bulletin et mémoires de l'Académie Royale de Médecine de Belgique, 142: 357-363. -12. Leukemogenesis by transactivating retroviruses : bovine leukemia virus as a model system. A. Burny, Y. Cleuter, C. Dandoy, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke and L. Willems (1987) Concepts and theories in carcinogenesis. Maskens, Ebbesen and Burny (eds). Excerpta Medica (Amsterdam, New York, Oxford), p 77-85. -13. Bovine leukemia: facts and hypothesis derived from the study of an infectious cancer. A. Burny, Y. Cleuter, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke, L. Willems and R. Thomas (1987) Cancer Surveys, 6: 139-159. -14. Etude de la région X du virus de la leucémie bovine. L. Willems (1988) Mémoire présenté en vue de l'obtention du grade de Docteur en Sciences agronomiques. Faculté des Sciences agronomiques de Gembloux, pp 154. -15. Bovine leukaemia: facts and hypotheses derived from the study of an infectious cancer. A. Burny, Y. Cleuter, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke, L. Willems and R. Thomas (1988). Vet Microbiol. 17:197-218. -16. Bovine leukaemia : facts and hypothesis derived from the study of an infectious cancer. A. Burny, Y. Cleuter, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke, L. Willems and R. Thomas (1988) Advances in veterinary science and comparative medecine, 32: 149-169. -17. Leukemogenesis by transacting retroviruses : bovine leukemia virus as a model system. A. Burny, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke and L. Willems (1988) Modern trends in virology. H. Bauer, H. Klenk and C. Scholtissek (eds). Springer Verlag Press (Berlin, Heidelberg), p 135-141. -18. Les techniques de clonage, le transfert de gènes et la régulation de l' expression chez les animaux domestiques. A. Burny, M. Chaput, V. Claes, R. Kettmann, D. Portetelle, R. Renaville et L. Willems (1989) Biotechnologie en selection animale. IRSIA. -19. Bovine leukemia : facts and hypothesis derived from the study of an infectious cancer. A. Burny, Y. Cleuter, R. Kettmann, M. Mammerickx, G. Marbaix, D. Portetelle, A. Van Den Broeke, L. Willems and R. Thomas (1990) Retroviruses biology and human disease. R. Gallo and F. Wong-Staal (eds). Dekker Press (New-York, Basel), p 9-32. -20. Leukemie van runderen: model van leukemie veroorzaakt door een retrovirus. L. Willems, A. Burny en R. Kettmann (1991) Kanker, 3: 96-97.

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-21. Leukaemia Viruses. A. Burny and L. Willems (1991) Encyclopedia of Immunology. I. Roitt and P. Delves (eds) Academic Press (New York), p 971-973. -22. Bovine Leukemia Virus. R. Kettmann, A. Burny, I. Callebaut, L. Droogmans, M. Mammerickx, L. Willems and D. Portetelle (1994) The Retroviridae.J. A. Levy (ed). Plenum Press (New York), 3: 39-81. -23. Bovine Leukemia Virus: biology and mode of transformation. A. Burny, L. Willems, I. Callebaut, E. Adam, I. Cludts, F. Dequiedt, L. Droogmans, C. Grimonpont, P. Kerkhofs, M. Mammerickx, D. Portetelle, A. Van Den Broeke and R. Kettmann (1994) Viruses and Cancer. A. Minson, J. Neil and M. McRae (eds). Cambridge University Press (London), p 213-234. -24. Le virus de la leucémie bovine: modèle de transformation par un rétrovirus transactivant. L. Willems (1994) Mémoire présenté en vue de l'obtention du grade d'Agrégé de l'Enseignement supérieur. Faculté des Sciences agronomiques de Gembloux, pp81. -25. Leukaemia Viruses. A. Burny, F. Bex, F. Dequiedt, E. Adam, JS. Gatot, P. Kerkhofs, R. Kettmann, D. Portetelle, A. Van Den Broeke and L. Willems (1998) Encyclopedia of Immunology, Second Edition. I. Roitt and P. Delves (eds). Academic Press (New York), p 1562-1565. -26. Bovine Leukemia virus as a model for Human T-cell leukemia virus. L. Willems, A. Burny, O. Dangoisse, D. Collete, F. Dequiedt, JS. Gatot, P. Kerkhofs, L. Lefebvre, C. Merezak, D. Portetelle, JC. Twizere and R. Kettmann (1999) Current Topics in Virology, 1: 139-167. -27. Genetic determinants of bovine leukemia virus pathogenesis. L. Willems, A. Burny, D. Collete, O. Dangoisse, F. Dequiedt, JS. Gatot, P. Kerkhofs, L. Lefebvre, C. Merezak, T. Peremans, JC. Twizere and R. Kettmann (2000) AIDS Research and Human Retroviruses, 16: 1787-1795. -28. Le BLV: un modèle d'étude pour les leucémies humaines. L. Willems (2004) Bulletin et mémoires de l'Académie Royale de Médecine de Belgique, 159: 473-478. -29. Le virus de la leucémie bovine et l'homéostasie du compartiment lymphocytaire périphérique. A. Florins, R. Kettmann et L. Willems (2007) Biotechnol. BASE 11: 69-78. -30. Homologies entre les deux rétrovirus BLV et HTLV-1 et développement d’une nouvelle approche thérapeutique basée sur la levée de la latence virale. N. Gillet, R. Kettmann et L. Willems (2007) BASE 11: 151–157. -31. Les chémokines et leurs récepteurs : rôle dans les infections virales et dans les pathologies cancéreuses. C. Burteau, L. Willems et R. Kettmann (2007) Biotechnol. BASE 11: 141–150. -32. Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human. N. Gillet, A. Florins, M. Boxus, C. Burteau, A. Nigro, F.

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Vandermeers, H. Balon, A. Bouzar, J. Defoiche, A. Burny, M. Reichert, R. Kettmann and L. Willems (2007) Retrovirology, 4: 18. -33. Dynamique cellulaire de la pathogenèse induite par le virus de la leucémie bovine. A. Florins, N. Gillet, M. Boxus, O. Verlaeten, A. Nigro, F. Vandermeers, C. Burteau, H. Balon, A. Bouzar, J. Defoiche, A. Burny, R. Kettmann et L. Willems (2007) Virologie, 11: 447-455. -34. The HTLV-1 Tax interactome. M. Boxus, JC. Twizere, S. Legros, JF. Dewulf, R. Kettmann and L. Willems (2008) Retrovirology, 5: 76. -35. How HTLV-1 may subvert miRNAs for persistence and transformation. A.B. Bouzar and L. Willems (2008) Retrovirology, 5: 101. -36. Involvement of epigenetic modifications in cancers: development of new therapeutic approaches. F. Vandermeers, R. Kettmann and Luc Willems (2008) BASE 12(2), 211-218. -37. Gene activation therapy: from the BLV model to HAM/TSP patients. A. Lezin, S. Olindo, G. Belrose, A. Signaté, R. Césaire, D. Smadja, D. Macallan, B. Asquith, C. Bangham, A. Bouzar, N. Gillet, J. Defoiche, A. Florins, O. Verlaeten, A. Burny and L. Willems (2009) Frontiers in Bioscience, S1: 205-215. -38. Reduced expression of cell cycle-associated genes in B lymphocytes purified from the peripheral blood of early-stage B chronic lymphocytic leukaemia (B-CLL) patients. J. Defoiche, A. Bouzar, D. Macallan and L. Willems (2009) British Journal of Haematology, 145: 426-428. -39. The 14th International Conference on Human Retrovirology: HTLV and related retroviruses. L. Willems (2009) Retrovirology, 6: 77. -40. Mechanisms of HTLV-1 persistence and transformation. M. Boxus and L. Willems (2009) British Journal of Cancer 101:1497-501.

-41. Facilitating studies of cell proliferation in chronic lymphocytic leukemia. D. Macallan, J. Defoiche and L. Willems (2010). Leukemia Research, 34:e273-4.

-42. In vivo ribosomal RNA turnover is down-regulated in leukaemic cells in chronic lymphocytic leukaemia. J. Defoiche, Y. Zhang, L. Lagneaux, L. Willems and D. Macallan (2010) British Journal of Haematology 151:192-195.

-43. Preventive and therapeutic strategies for bovine leukemia virus: lessons for HTLV. S. Rodriguez, A. Florins, N. Gillet, A. de Brogniez, M-T. Sánchez-Alcaraz, M. Boxus, F. Boulanger, G. Gutiérrez, K. Trono, I. Alvarez, L. Vagnoni and L. Willems (2011) Viruses 3: 1210-1248.

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-44. How the DNA damage response determines the fate of HTLV-1 Tax-expressing cells. M. Boxus and L. Willems (2012) Retrovirology 9:2.

-45. Transformation by deltaretroviruses: mechanisms and therapies. L. Willems (2012) Proceedings of the Belgian Royal Academies of Medicine 1: 157-165.

-46. WIP1 deficiency inhibits HTLV-1 Tax oncogenesis: novel therapeutic prospects for treatment of ATL? N. Gillet, A. Carpentier, P-Y. Barez and L. Willems (2012) Retrovirology 9:115.

-47. The role of epigenetics in malignant pleural mesothelioma. F. Vandermeers, S. Neelature Sriramareddy, C. Costa, R. Hubaux, J-P Cosse and L. Willems (2013) Lung Cancer 81: 311-318

-48. Epigenetic modulators mitigate angiogenesis through a complex transcriptomic network. T.V. Shiva Shankar and L. Willems (2014) Vascular pharmacology 60: 57-66

-49. Vaccination against δ-Retroviruses: the bovine leukemia virus paradigm. G. Gutiérrez, S. Rodríguez, A. de Brogniez, N. Gillet, R. Golime, A. Burny, J-P Jaworski, I. Alvarez, L. Vagnoni, K. Trono and L. Willems (2014) Viruses 6: 2416-2427

-50. Modes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and Persistence. A. Carpentier, PY. Barez †, M. Hamaidia, H. Gazon, A. de Brogniez, S. Perike, N. Gillet and L. Willems (2015) Viruses 7: 3603-3624

-51. APOBEC3 interference during replication of viral genomes. L. Willems and N. Gillet (2015) Viruses 7: 2999-3018

-52. Structural characterization, technological functionality and physiological aspects of fungal β-D-glucans: a review. C. Borchani, F. Fonteyn, G. Jamin, J. Destain, L. Willems, P. Paquot, C. Blecker, P. Thonart, (2015) Critical Reviews in Food Science & Nutrition, in press

-53. Improvement of malignant pleural mesothelioma immunotherapy by epigenetic modulators. M. Hamaidia, B. Staumont, B. Duysinx, R. Louis and L. Willems (2016) Current Topics in Medicinal Chemistry 16: 7, in press

-54. From Valeriana officinalis to cancer therapy: the success of a bio-sourced compound. M. Hamaidia, P-Y. Barez, A. Carpentier, S. Lebecque, K. Miazek, Aman Paul, S. Reddy, B. Staumont, S. Danthine, M. Deleu, M. Frederich, E. De Pauw, P. Delaplace, F. Delvigne, D. Goffin, M. Ongena, B. Duysinx, R. Louis, J-P. Cosse and Luc Willems. BASE, in press

-55. Recent advances in BLV research. P-Y. Barez, A. De Brogniez, A. Carpentier, H. Gazon, N. Gillet, G. Gutiérrez, M. Hamaidia, J-R. Jacques, S. Perike, S. Neelature Sriramareddy, N. Renotte, B. Staumont, M. Reichert, K. Trono, L. Willems. Viruses, in press

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PAPERS IN INTERNATIONAL PERIODICALS

-1. The 3' region of bovine leukemia virus genome encodes a transactivator protein. C. Rosen, J. Sodroski, L. Willems, R. Kettmann, K. Campbell, R. Zaya, A. Burny and W. Haseltine (1986) Embo J., 5: 2585-2589. -2. Identification of the bovine leukemia virus transactivating protein (p34). L. Willems, R. Kettmann, D. Portetelle and A. Burny (1987) Haematology and blood transfusion. Modern trends in human leukemia VII. Neth, Gallo, Greaves and Kabisch (eds). Springer Verlag Berlin Heidelberg, 31: 482-487. -3. Expression of a cDNA clone corresponding to the long open reading frame (XBL-1) of the bovine leukemia virus. L. Willems, C. Bruck, D. Portetelle, A. Burny and R. Kettmann (1987) Virology, 160: 55-59. -4. Expression of the pX products of the bovine leukemia virus. L. Willems, G. Chen, R. Kettmann and A. Burny (1987) Cancer Letters (suppl.), 36: 7. -5. The bovine leukemia virus p34 is a transactivator protein. L. Willems, A. Gegonne, G. Chen, A. Burny, R. Kettmann and J. Ghysdael (1987) Embo J., 6: 3385-3389. -6. Expression in bacteria of beta-galactosidase fusion proteins carrying antigenic determinants of the two X gene products of bovine leukemia virus. L. Willems, G. Chen, A. Burny and R. Kettmann (1988) Leukemia, 2: 1-5. -7. Structural and functional characterization of mutants of the bovine leukemia virus transactivator protein p34. L. Willems, G. Chen, D. Portetelle, R. Mamoun, A. Burny and R. Kettmann (1989) Virology, 171: 615-618. -8. Synthesis of functional bovine leukemia p34tax protein by recombinant baculoviruses. G. Chen, L. Willems, D. Portetelle, K. Willard-Gallo, A. Burny, D. Gheysen and R. Kettmann (1989) Virology, 173: 343-347. -9. Expression of the bovine leukemia virus transactivator protein by a recombinant vaccinia virus. L. Willems, C. Letellier, M. Gonze, R. Martin, R. Kettmann, A. Burny and G. Meulemans (1989) Vet. Imm. Immunopath., 22: 201-211. -10. Cooperation between Bovine Leukemia Virus transactivator protein and Ha-ras oncogene product in cellular transformation. L. Willems, H. Heremans, G. Chen, D. Portetelle, A. Billiau, A. Burny and R. Kettmann (1990) Embo J., 9: 1577-1581. -11. The amino acid (157-197) peptide segment of Bovine Leukemia Virus p34tax encompass a leucine-rich globally neutral activation domain. L. Willems, A. Burny and R. Kettmann (1991) Oncogene, 6: 159-163.

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-12. The bovine leukemia virus tax gene contains an enhancer sequence. L. Willems, P-C. Romond, J. Ghysdael, A. Burny and R. Kettmann (1991) Virology, 182: 130-134. -13. Nucleotide sequence of the bovine cyclic-AMP responsive DNA binding protein (CREB2) cDNA. L. Willems, R. Kettmann, G. Chen, D. Portetelle, A. Burny and D. Derse (1991) DNA Sequence, 1: 415-417. -14. A cyclic AMP-responsive DNA binding protein (CREB2) is a cellular transactivator of the bovine leukemia virus long terminal repeat. L. Willems, R. Kettmann, G. Chen, D. Portetelle, A. Burny and D. Derse (1992) Journal of Virology, 66: 766-772. -15. Mutations in the bovine leukemia tax protein can abrogate the LTR-directed transactivating activity without concomitant loss of transforming potential. L. Willems, C. Grimonpont, H. Heremans, N. Rebeyrotte, G. Chen, D. Portetelle, A. Burny and R. Kettmann (1992) Proc. Natl. Acad. Sci. U.S.A., 89: 3957-3961. -16. Fusogenic segments of bovine leukemia virus and simian immunodeficiency virus are interchangeable and mediate fusion by means of oblique insertion in the lipid bilayer of their target cells. V. Voneche, D. Portetelle, R. Kettmann, L. Willems, K. Limbach, E. Paoletti, J-M. Ruysschaert, A. Burny and R. Brasseur (1992) Proc. Natl. Acad. Sci. U.S.A., 89: 3810-3814. -17. In vivo transfection of bovine leukemia provirus into sheep. L. Willems, D. Portetelle, P. Kerkhofs, G. Chen, A. Burny, M. Mammerickx and R. Kettmann (1992) Virology, 189: 775-777. -18. Bovine leukemia virus, an animal model for the study of intrastrain variability. L. Willems, E. Thienpont, P. Kerkhofs, A. Burny, M. Mammerickx and R. Kettmann (1993) Journal of Virology, 67: 1086-1089. -19. In vivo infection of sheep by bovine leukemia virus mutants. L. Willems, R. Kettmann, F. Dequiedt, D. Portetelle, V. Voneche, I. Cornil, P. Kerkhofs, A. Burny and M. Mammerickx (1993) Journal of Virology, 67: 4078-4085. -20. Involvement of the cyclic AMP-responsive element binding protein in bovine leukemia virus expression in vivo. E. Adam, P. Kerkhofs, M. Mammerickx, R. Kettmann, A. Burny, L. Droogmans and L. Willems (1994) Journal of Virology, 68: 5845-5853. -21. Attenuation of bovine leukemia virus by deletion of R3 and G4 open reading frames. L. Willems, P. Kerkhofs, F. Dequiedt, D. Portetelle, M. Mammerickx, A. Burny and R. Kettmann (1994) Proc. Natl. Acad. Sci. U.S.A., 91: 11532-11536. -22. Expression of interleukin 6 receptors and interleukin 6 mRNA by bovine leukaemia virus-induced tumor cells. L. Droogmans, I. Cludts, Y. Cleuter, P. Kerkhofs, E. Adam, L. Willems, R. Kettmann and A. Burny (1994) Cytokine, 6: 641-646. -23. Nucleotide sequence of the ovine p53 tumor-suppressor cDNA and its genomic organization. F. Dequiedt, R. Kettmann, A. Burny and L. Willems (1995) DNA Sequence, 5: 255-259.

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-24. Nucleotide sequence of the bovine p53 tumor-suppressor cDNA. F. Dequiedt, L. Willems, A. Burny and R. Kettmann (1995) DNA Sequence, 5: 261-264. -25. Lack of LTR and env genetic variation during bovine leukemia virus induced leukemogenesis. L. Willems, P. Kerkhofs, A. Burny, M. Mammerickx and R. Kettmann (1995) Virology, 206: 769-772. -26. Rat embryo fibroblasts immortalization by bovine leukemia virus Tax protein. L. Willems, H. Heremans, A. Burny and R. Kettmann (1995) Methods in cell science, 2: 137-140. -27. Mutations of the p53 tumor-suppressor gene are frequently involved during bovine leukemia virus (BLV)-induced leukemogenesis in cattle but not in sheep. F. Dequiedt, R. Kettmann, A. Burny and L. Willems (1995) Virology, 209: 676-683. -28. The YXXL signalling motifs of the bovine leukemia virus transmembrane protein are required for in vivo infection and maintenance of high virus loads. L. Willems, J.S. Gatot, M. Mammerickx, D. Portetelle, A. Burny, P. Kerkhofs and R. Kettmann (1995) Journal of Virology, 69: 4137-4141. -29. Modulation of CD3-γ gene expression after HIV type 1 infection of the WE17/10 cell line is progressive and occurs in concert with decreased production of viral p24 antigen. K. Willard-Gallo, C. Delmelle-Wibaut, I. Segura-Zapata, M. Janssens, L. Willems and R. Kettmann (1996) AIDS Res. and Hum. Retr., 12: 715-725. -30. The CREB, ATF-1 and ATF-2 transcription factors from bovine leukemia virus-infected B lymphocytes activate viral expression. E. Adam, P. Kerkhofs, M. Mammerickx, A. Burny, R. Kettmann and L. Willems (1996) Journal of Virology, 70: 1990-1999. -31. Cellular pathways involved in the ex vivo expression of bovine leukemia virus. P. Kerkhofs, E. Adam, L. Droogmans, D. Portetelle, M. Mammerickx, A. Burny, R. Kettmann and L. Willems (1996) Journal of Virology, 70: 2170-2177. -32. The cloning and sequencing of an ovine c-myc cDNA. V. Kiermer, F. Dequiedt, R. Masengo, Y. Cleuter, D. Briclet, M. Ciesolka, A. Van den Broeke, L. Willems, R. Kettmann, A. Burny and L. Droogmans (1997) DNA Sequence, 7: 235-238. -33. Both wild-type and strongly attenuated bovine leukemia viruses protect peripheral blood mononuclear cells from apoptosis. F. Dequiedt, E. Hanon, P. Kerkhofs, P.P. Pastoret, D. Portetelle, A. Burny, R. Kettmann and L. Willems (1997) Journal of Virology, 71: 630-639. -34. The major homology region of bovine leukemia virus p24gag is required for virus infectivity in vivo. L. Willems, P. Kerkhofs, L. Attenelle, A. Burny, D. Portetelle and R. Kettmann (1997) J. Gen. Virol., 78: 637-640. -35. Bovine herpesvirus-induced apoptosis occurs at the G0/G1 phase of the cell cycle. E. Hanon, S. Hoornaert, F. Dequiedt, A. Vanderplasschen, J. Lyaku, L. Willems and P.P. Pastoret (1997) Virology, 232: 351-358.

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-36. Lack of mutations in the WAF1/CIP gene during bovine leukemia virus-induced leukemogenesis. F. Dequiedt, L. Willems, P. Kerkhofs, A. Burny and R. Kettmann (1997) Vett. Imm. Imm., 59: 311-322. -37. Phosphorylation of bovine leukemia virus Tax protein is required for in vitro transformation but not for transactivation. L. Willems, C. Grimonpont, P. Kerkhofs, C. Capiau, D. Gheysen, K. Conrath, R. Roussef, R. Mamoun, D. Portetelle, A. Burny, E. Adam, L. Lefebvre, J-C. Twizere, H. Heremans and R. Kettmann (1998) Oncogene, 16: 2165-2176. -38. In vitro and in vivo oncogenic potential of bovine leukemia virus G4 protein. P. Kerkhofs, H. Heremans, A. Burny, R. Kettmann and L. Willems (1998) Journal of Virology, 72: 2554-2559. -39. Conservative mutations in the immunosuppressive region of the bovine leukemia virus transmembrane protein affect fusion but not infectivity in vivo. JS. Gatot, I. Callebaut, JP. Mornon, D. Portetelle, A. Burny, P. Kerkhofs, R. Kettmann and L. Willems (1998) The Journal of Biological Chemistry, 273: 12870-12880. -40. Bovine Leukemia Virus -induced persistent lymphocytosis in cattle does not correlate with increased ex vivo survival of B lymphocytes. F. Dequiedt, G. Cantor, V. Hamilton, S. Pritchard, W. Davis, P. Kerkhofs, A. Burny, R. Kettmann and L. Willems (1999) Journal of Virology, 73: 1127-1137. -41. Long-term protection against bovine leukemia virus replication in cattle and in sheep. P. Kerkhofs, JS. Gatot, K. Knapen, M. Mammerickx, A. Burny, D. Portetelle, L. Willems and R. Kettmann (2000) Journal of General Virology, 81: 957-963. -42. Protective effects of a live attenuated bovine leukemia virus vaccine with deletion in the R3 and G4 genes. M. Reichert, G. Cantor, L. Willems and R. Kettmann (2000) Journal of General Virology, 81: 965-969. -43. A multipotential β-1,6-N-acetylglucosaminyl-transferase is encoded by Bovine Herpesvirus type 4. A. Vanderplasschen, N. Markine-Goriaynoff, P. Lomonte, M. Suzuki, N. Hiraoka, JC. Yeh, F. Bureau, L. Willems, E. Thiry, M. Fukuda and PP. Pastoret (2000) Proc. Natl. Acad. Sci. U.S.A., 97: 5756-5761. -44. Discordance between bovine leukemia virus Tax immortalization in vitro and oncogenicity in vivo. JC. Twizere, P. Kerkhofs, A. Burny, D. Portetelle, R. Kettmann and L. Willems (2000) Journal of Virology, 74: 9895-9902. -45. CD5 is dissociated from the B-cell receptor in B cells from bovine leukemia virus-infected, persistently lymphocytotic cattle: consequences to B-cell receptor-mediated apoptosis. G. Cantor, S. Pritchard, F. Dequiedt, L. Willems, R. Kettmann and W. Davis (2001) Journal of Virology, 75: 1689-1696. -46. Suboptimal enhancer sequences are required for efficient bovine leukemia virus propagation in vivo: implications for viral latency. C. Merezak, C. Pierreux, E. Adam, F. Lemaigre, G.G.

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Rousseau, C. Calomme, C. van Lint, D. Christophe, P. Kerkhofs, A. Burny, R. Kettmann and L. Willems (2001) Journal of Virology, 75: 6977-6988. -47. Role of the proline-rich motif of bovine leukemia virus transmembrane protein gp30 in viral load and pathogenicity in sheep. M. Reichert, A. Winnicka, L. Willems, R. Kettmann and G. Cantor (2001) Journal of Virology, 75: 8082-8089. -48. Oncoviral BLV G4 and HTLV-1 p13II proteins interact with farnesyl pyrophosphate synthetase. L. Lefebvre, A. Vanderplasschen, V. Ciminale, H. Heremans, O. Dangoisse, JC. Jauniaux, JF. Toussaint, V. Zelnik, A. Burny, R. Kettmann and L. Willems (2001) Journal of Virology, 76: 1400-1414. -49. Inhibition of histone deacetylase induces bovine leukemia virus expression in vitro and in vivo. C. Merezak, M. Reichert, C. van Lint, P. Kerkhofs, D. Portetelle, L. Willems and R. Kettmann (2002) Journal of Virology, 76: 5034-5042. -50. Increased cell proliferation - but not reduced cell death - induces lymphocytosis in Bovine Leukemia Virus-infected sheep. C. Debacq, B. Asquith, P. Kerkhofs, D. Portetelle, A. Burny, R. Kettmann and L. Willems (2002) Proc. Natl. Acad. Sci. U.S.A., 99: 10048-10053. -51. Subcellular localization of the BLV R3 and G4 accessory proteins. L. Lefebvre, V. Ciminale, A. Vanderplasschen, D. d'Agostino, A. Burny, L. Willems and R. Kettmann (2002) Journal of Virology, 76: 7843-7854. -52. Bovine leukemia virus SU protein interacts with zinc, and mutations within two interacting regions affect viral fusion and infectivity differently in vivo. JS. Gatot, I. Callebaut, C. van Lint, D. Demonte, P. Kerkhofs, D. Portetelle, A. Burny, L. Willems and R. Kettmann (2002) Journal of Virology, 76: 7956-7967. -53. Lymphocyte kinetics, the interpretation of labelling data. B. Asquith, C. Debacq, D. Macallan, L. Willems and C. Bangham (2002) Trends in Immunology, 23: 596-601. -54. Reduced cell turnover in bovine leukemia virus-infected, persistently lymphocytotic cattle. C. Debacq, B. Asquith, M. Reichert, A. Burny, R. Kettmann and L. Willems (2003) Journal of Virology, 77: 13073-13083. -55. Interaction of retroviral tax oncoproteins with tristetraprolin and regulation of TNF-α expression. JC. Twizere, V. Kruys, L. Lefèbvre, A. Vanderplasschen, D. Collete, C. Debacq, WI S. Lai, JC. Jauniaux, L. Bernstein, OJ. Semmes, A. Burny, PJ. Blackshear, R. Kettmann and L. Willems (2003) The Journal of the National Cancer Institute, 95: 1846-1859. -56. Investigation of the Susceptibility of Human Cell Lines to Bovine Herpesvirus 4 Infection: Demonstration that Human Cells Can Support a Nonpermissive Persistent Infection Which Protects Them against Tumor Necrosis Factor Alpha-Induced Apoptosis. L. Gillet, F. Minner, B. Detry, F. Farnir, L. Willems, M. Lambot, E. Thiry, P-P. Pastoret, F. Schynts and A. Vanderplasschen (2004) Journal of Virology, 78: 2336-2347.

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-57. Involvement of glutathione as a mechanism of indirect protection against spontaneous ex vivo apoptosis associated with Bovine Leukemia Virus. T. Sanchez Alcaraz, P. Kerkhofs, M. Reichert, R. Kettmann and L. Willems (2004) Journal of Virology, 78: 6181-6189. -58. Suppression of tumor growth and cell proliferation by p13II, a mitochondrial protein of human T cell leukaemia virus type 1. M. Silic-Benussi, I. Cavallari, T. Zorzan, E. Rossi, H. Hiraragi, A. Rosato, K. Horie, D. Saggioro, MD. Lairmore, L. Willems, L. Chieco-Bianchi, DM. d'Agostino and V. Ciminale (2004) Proc. Natl. Acad. Sci. U.S.A., 101: 6629-6634. -59. Reduced proviral loads during primo-infection of sheep by Bovine Leukemia virus attenuated mutants. C. Debacq, MT. Sanchez Alcaraz, F. Mortreux, P. Kerkhofs, R. Kettmann and L. Willems (2004) Retrovirology, 1: 31. -60. Overlapping CRE and E Box Motifs in the Enhancer Sequences of the Bovine Leukemia Virus 5' Long Terminal Repeat Are Critical for Basal and Acetylation-Dependent Transcriptional Activity of the Viral Promoter: Implications for Viral Latency. C. Calomme, A. Dekoninck, S. Nizet, E. Adam, TL. Nguyen, A. Van Den Broeke, L. Willems, R. Kettmann, A. Burny and C. Van Lint (2004) Journal of Virology, 78: 13848-13864. -61. Fate of premalignant clones during the asymptomatic phase preceding lymphoid malignancy. V. Moules, C. Pomier, D. Sibon, AS. Gabet, M. Reichert, P. Kerkhofs, L. Willems, F. Mortreux and E. Wattel (2005) Cancer Res., 65: 1234-43. -62. The homeobox protein MSX2 interacts with tax oncoproteins and represses their transactivation activity. JC. Twizere, L. Lefebvre, D. Collete, C. Debacq, P. Urbain, H. Heremans, JC. Jauniaux, A. Burny, L. Willems and R. Kettmann (2005) J. Biol. Chem., 280: 29804-11. -63. Valproate activates bovine leukemia virus gene expression, triggers apoptosis and induces leukemia/lymphoma regression in vivo. A. Achachi, A. Florins, N. Gillet, C. Debacq, P. Urbain, G. Manfouo Foutsop, F. Vandermeers, A. Jasik, M. Reichert, P. Kerkhofs, L. Lagneaux, A. Burny, R. Kettmann and L. Willems (2005) Proc. Natl. Acad. Sci. U.S.A., 102: 10309-10314. -64. Reduced cell turnover in lymphocytic monkeys infected by human T-lymphotropic virus type 1. C. Debacq, J-M. Héraud, B. Asquith, C. Bangham, F. Merien, V. Moules, F. Mortreux, E. Wattel, A. Burny, R. Kettmann, M. Kazanji and L. Willems (2005) Oncogene, 24: 7514-7523. -65. Quantifying lymphocyte kinetics in vivo using CFSE. B. Asquith, C. Debacq, A. Florins, N. Gillet, T. Sanchez-Alcaraz, A. Mosley and L. Willems (2006) Proceedings of the Royal Society of London, 273: 1165-1171. -66. Peripheral blood B cell death compensates for excessive proliferation in lymphoid tissues and maintains homeostasis in Bovine Leukemia Virus infected sheep. C. Debacq, N. Gillet, B. Asquith, MT. Sanchez-Alcaraz, A. Florins, M. Boxus, I. Schwartz-Cornil, M. Bonneau, G. Jean, P. Kerkhofs, J. Hay, A. Théwis, R. Kettmann and L. Willems (2006) Journal of Virology, 80: 9710-9719.

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-67. Spleen-dependent turnover of CD11b peripheral blood B lymphocytes in BLV-infected sheep. A. Florins, N. Gillet, B. Asquith, C. Debacq, G. Jean, I. Schwartz-Cornil, M. Bonneau, A. Burny, M. Reichert, R. Kettmann and L. Willems (2006) Journal of Virology, 80: 11998-2008. -68. Cell dynamics and immune response to BLV infection: a unifying model. A. Florins, N. Gillet, B. Asquith, M. Boxus, C. Burteau, JC. Twizere, P. Urbain, F. Vandermeers, C. Debacq, MT. Sanchez-Alcaraz, I. Schwartz-Cornil, P. Kerkhofs, G. Jean, A. Théwis, J. Hay, F. Mortreux, E. Wattel, M. Reichert, A. Burny, R. Kettmann, C. Bangham and L. Willems (2007) Frontiers in Bioscience, 12: 1520-31. -69. Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling. JC. Twizere, JY. Springael, M. Boxus, A. Burny, F. Dequiedt, JF. Dewulf, J. Duchateau, D. Portetelle, P. Urbain, C. Van Lint, PL. Green, R. Mahieux, M. Parmentier, L. Willems and R. Kettmann (2007) Blood, 109: 1051-1060. -70. Even BLV attenuated proviruses can be pathogenic in sheep. A. Florins, N. Gillet, M. Boxus, P. Kerkhofs, R. Kettmann and L. Willems (2007) Journal of Virology , 81: 10195-10200. -71. Histone deacetylase mediated transcriptional activation reduces proviral loads in HTLV-1-associated myelopathy/tropical spastic paraparesis patients. A. Lezin, N. Gillet, S. Olindo, N. Grandvaux, O. Verlaeten, M. de Carvalho de Bittencourt, B. Asquith, J. Hiscott, A. Burny, D. Smadja, R. Césaire and L. Willems (2007) Blood, 110: 3722-3728. -72. Valproic acid induces apoptosis in chronic lymphocytic leukemia cells through activation of the death receptor pathway and potentiates TRAIL response. L. Lagneaux, N. Gillet, B. Stamatopoulos, A. Delforge, M. Dejeneffe, M. Massy, N. Meuleman, A. Kentos, P. Martiat, L. Willems and D. Bron (2007) Exp. Hematol., 35: 1527-1537. -73. Early and transient reverse transcription during primary deltaretroviral infection of sheep. C. Pomier, M.T. Sanchez Alcaraz, C. Debacq, A. Lançon, P. Kerkhofs, L. Willems, E. Wattel and F. Mortreux (2008) Retrovirology, 5: 16. -74. Reduction of B cell turnover in chronic lymphocytic leukemia. J. Defoiche, C. Debacq, B. Asquith, Y. Zhang, A. Burny, D. Bron, L. Lagneaux, D. Macallan and L. Willems (2008) British Journal of Haematology, 143: 240-247. -75. Emphasis on cell turnover in two hosts infected by bovine leukemia virus: a rationale for host susceptibility to disease latency and frequency. A. Florins, M. Boxus, F. Vandermeers, O. Verlaeten, A. Bouzar, J. Defoiche, R. Hubaux , A. Burny, R. Kettmann and L. Willems (2008) Vett. Imm. Imm., 125: 1-7. -76. Valproate synergizes with purine nucleoside analogues to induce apoptosis of B-chronic lymphocytic leukaemia cells. A. Baya Bouzar, M. Boxus, J. Defoiche, H. Balon, G. Berchem, D. Macallan, R. Pettengell, F. Willis, A. Burny, L. Lagneaux, D. Bron, B. Chatelain, C. Chatelain and L. Willems (2009) British Journal of Haematology, 144: 41-52.

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-77. A dose-effect relationship for deltaretrovirus-dependent leukemogenesis in sheep. C. Pomier, M. Sanchez Alcaraz, C. Debacq, A. Lancon, P. Kerkhofs, L. Willems, E. Wattel and F. Mortreux (2009) Retrovirology, 6: 30. -78. Valproate, in combination with pemetrexed and cisplatin, provides additional efficacy to the treatment of malignant mesothelioma. F. Vandermeers, P. Hubert, P. Delvenne, C. Mascaux, B. Grigoriu, A. Burny, A. Scherpereel and L. Willems (2009) Clinical Cancer Research, 15: 2818-2828. -79. Measurement of ribosomal RNA turnover in vivo using deuterium-labeled glucose. J. Defoiche, Y. Zhang, L. Lagneaux, R. Pettengell, L. Willems and D. Macallan (2009) Clinical Chemistry, 55: 1824-1833. -80. Earlier Onset of δ-retrovirus-induced leukemia after splenectomy. A. Florins, M. Reichert, B. Asquith, A. Bouzar, G. Jean, C. François, A. Jasik, A. Burny, R. Kettmann and L. Willems (2009) PLoS One, 4: e6943. -81. Reduced levels of reactive oxygen species correlate with inhibition of apoptosis, rise in thioredoxin expression and increased bovine leukemia virus proviral loads. A. Bouzar, M. Boxus, A. Florins, C. François, M. Reichert and L. Willems (2009) Retrovirology, 6: 102. -82. Preclinical evidences for a beneficial impact of valproate in response of small cell lung cancer to first-line chemotherapy. R. Hubaux, F. Vandermeers, C. Crisanti, V. Kapoor, A. Burny, C. Mascaux, S.M. Albelda and L. Willems (2010) European Journal of Cancer 46: 1724-1734. -83. Valproic acid plus doxorubicin: effective therapy for progressing mesothelioma. A ELCWP phase II study. A. Scherpereel, T. Berghmans, J.J. Lafitte, B. Colinet, M. Richez, Y. Bonduelle, A.P. Meert, X. Dhalluin, N. Leclercq, M. Paesmans, L. Willems, J.P. Sculier (2011) European Respiratory Journal 37:129-135. -84. Opposite effects of valproate on Tax and HBZ expression in HTLV-1 and HAM/TSPT lymphocytes. G. Belrose, A. Gross, S. Olindo, A. Lézin, M. Dueymes, I. Komla-Soukha, D. Smadja, Y. Tanaka, L. Willems, JM. Mesnard, JM. Peloponese and R. Césaire (2011) Blood 118 :2483-2491. -85. Safety of long-term treatment of HAM/TSP patients with valproic acid. S. Olindo, G. Belrose, N. Gillet S. Rodriguez, M. Boxus, O. Verlaeten, B. Asquith, C. Bangham, A. Signaté, D. Smadja, A. Lezin, R. Césaire and L. Willems (2011) Blood 118:6306-6309. -86. Viral expression directs the fate of B cells in BLV-infected sheep. A. Florins, A. de Brogniez, M. Elemans , A-B. Bouzar, C. François, M. Reichert, B. Asquith and L. Willems (2012) Journal of Virology 86:621-4. -87. Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program. M. Boxus, J-C. Twizere, S. Legros, R. Kettmann and L. Willems (2012) Blood 119:151-160.

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-88. Chemoresistance to valproate treatment of bovine leukemia virus-infected sheep; identification of improved HDAC inhibitors. N. Gillet, F. Vandermeers, A. de Brogniez, A. Florins, A. Nigro, C. François, A. Bouzar, O. Verlaeten, J. Wouters, E. Stern, D. Lambert and L. Willems (2012) Pathogens 1:65-82. -89. Acetylation at lysine 346 controls the transforming activity of the HTLV-1 Tax oncoprotein in the Rat-1 fibroblast model. J. Lodewick, C. Sampaio, M. Boxus, A-S Rinaldi, K. Coulonval, L. Willems, P. Roger, F. Bex (2013) Retrovirology 10:75 -90. Identification of microRNA-based signatures for response and survival for non-small cell lung cancer treated with cisplatin-vinorelbine: a ELCWP prospective study. T. Berghmans, L. Ameye, L. Willems, M. Paesmans, C. Mascaux, JJ. Lafitte, AP. Meert, A. Scherpereel, A.B. Cortot, I. CsToth, T. Dernies, L. Toussaint, N. Leclercq and JP. Sculier (2013) Lung Cancer, 81:311-318. -91. Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection. N. Gillet, G. Gutiérrez, S. Rodriguez, A. de Brogniez, N. Renotte, I. Alvarez, K. Trono and L. Willems (2013) PLoS Pathogens, 9(10):e1003687. -92. Rates of CTL killing in chronic viral infection in vivo. M. Elemans, A. Florins, L. Willems and B. Asquith (2014) PLOS Computational Biology 10:e1003534. -93. Prospective validation obtained in a similar group of patients and with similar high throughput biological tests failed to confirm signatures for prediction of response to chemotherapy and survival in advanced NSCLC: a prospective study from the European Lung Cancer Working Party. T. Berghmans, L. Ameye, JJ Lafitte, B. Colinet, A. Cortot, I. CsToth, S. Holbrechts, J. Lecomte, C. Mascaux, AP. Meert, M. Paesmans, M. Richez, A. Scherpereel, C. Tulippe, L. Willems, T. Dernies, N. Leclercq and JP. Sculier (2015) Frontiers in Oncology, in press. -94. Mutation of a single envelope N-linked glycosylation site enhances the pathogenicity of bovine leukemia virus. A. de Brogniez, AB. Bouzar, JR. Jacques, JP. Cosse, N. Gillet, I. Callebaut, M. Reichert and L. Willems (2015) Journal of Virology 89:8945-8956. -95. N-Hydroxy-6-(5-nitro-naphtalimide)-hexanamide inhibits lysine deacetylation, mitigates angiogenesis and reduces tumor growth . T.V. Shiva Shankar, B. Sulka, P. Hubert, R. Hubaux, P. Delvenne, H. Pendeville, Irving Boittiaux, Didier M. Lambert, Johan Wouters, C. Maillard, S. Blacher, A. Noël, I. Struman and L. Willems (2015) Journal of Cancer Sciences, 2:11. -96. Doxorubicin, cyclophosphamide, vindesine with valproic acid for refractory/relapsing SCLC: a phase II study by the European Lung Cancer Working Party. T. Berghmans, JJ. Lafitte, A. Scherpereel, M. Paesmans, L. Ameye, AP. Meert, B ; Colinet, C. Tulippe, R. Hubaux, L. Willems, N. Leclercq, JP. Sculier (2015) European Respiratory Journal Open Research, 1: 00028-2015.

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-97. Valproic acid improves second line regimen of SCLC in preclinical models. R. Hubaux, F. Vandermeers, JP. Cosse, C. Crisanti, V. Kapoor, S. Albelda, C. Mascaux, P. Delvenne, P. Hubert and L. Willems (2015) European Respiratory Journal Open Research, 1: 00028-2015. Summary 55 review papers and 97 research articles over a 31 years career Bibliometrics Total citations: 2446 H index: 32

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PATENTS A LIFE ATTENUATED VACCINE AGAINST BOVINE LEUKEMIA VIRUS: EP13156921.2 - PCT/EP2014/053855 Abstract Although eradicated from Europe, bovine leukemia virus (BLV) is responsible for important economic losses worldwide. There is currently no efficient vaccine that protects against BLV infection. Previous vaccine candidates faced problems of efficacy (i.e. only a fraction of animals were protected), persistence (i.e. rapid decrease of immune protection), cost (e.g. production of purified proteins) or safety (e.g. genetically modified hybrid viruses). In this context, we propose a novel strategy based on the use of a live-attenuated BLV provirus. The rationale behind this strategy relies on the deletion of genes required to induce pathogenesis maintaining integrity of those involved in infectivity. We have identified a BLV deleted provirus that is infectious in cattle but replicates at reduced levels in cows as shown by real-time quantitative PCR. The deletant elicits a strong anti-BLV immune response as indicated by wild-type antibody titers. The deletant does not spread to uninfected sentinels maintained during 3 years in the same herd supporting biosafety of the vaccine. Passive antibodies are transmitted to the newborn calves via the maternal colostrum. This anti-viral passive immunity persists during several months in the calves. However, the BLV deletant does not transmit from cows to calves as demonstrated by nested PCR. Finally, vaccinated animals but not uninfected controls resist challenge by a wild type BLV virus. In conclusion, we have identified a safe BLV deletant with impaired transmissibility that protects efficiently against BLV infection.