CIRM Activity Report 2016 CIRM scientific activity report 01/2016 to 12/2016 Confidential -­‐ 1 CIRM Activity Report 2016 TABLE OF CONTENT 1. Introduction 2. CIRM 1.1. Introduction 2.1. Current composition of the CIRM laboratories 2.2.1. Analysis of Medicines laboratory (LAM) 2.2.2. Analytical Chemistry laboratory (LCA) 2.2.3. ATC-­‐Pharma (ATC) 2.2.4. Clinical Chemistry laboratory 2.2.5. Clinical, Forensic, Environmental and Industrial, Toxicology laboratory 2.2.6. Clinical Microbiology laboratory 2.2.7. Clinical Pharmacology laboratory 2.2.8. Hospital and Clinical Pharmacology Unit 2.2.9. Quality Assurance Unit 2.2.10. Pharmaceutical Chemistry laboratory (LCP) 2.2.11. Pharmaceutical Technology and Biopharmacy laboratory (LTBP) 2.2.12. Pharmacognosy laboratory (LPG) 2.2.13. Tumors and Development Biology laboratory (LBTD) 2.2.14. Biological and Industrial Chemistry laboratory 2.2.15. Oxygen Biochemistry Group 3. Research highlights from the CIRM 3.1. Introduction to the unifying thematics 3.2. Target and lead discovery (removed for confidentiality, only provided to the external advisory board) 3.3. Biopharmaceutics (removed for confidentiality, only provided to the external advisory board) 3.4. Nanomedicine (removed for confidentiality, only provided to the external advisory board) 3.5. Personalized medicine (removed for confidentiality, only provided to the external advisory board) 4. Scientific activities in the CIRM laboratories 4.1. Analysis of Medicines laboratory (LAM) 4.1.1. Main publications 4.1.2. Other publications 4.1.3. Patents 4.1.4. PhD completed 4.1.5. Grants and funds 4.1.6. Participations and invitations to congresses, seminars and research agencies 4.2. Analytical Chemistry laboratory (LCA) 4.2.1. Main publications 4.2.2. Other publications 4.2.3. Patents 4.2.4. PhD completed 4.2.5. Grants and funds 4.2.6. Participations and invitations to congresses, seminars and research agencies 4.3. ATC-­‐Pharma (ATC) 4.3.1. Main publications 4.3.2. Other publications 4.3.3. Patents 4.3.4. PhD completed 4.3.5. Grants and funds 4.3.6. Participations and invitations to congresses, seminars and research agencies 4.4. Clinical Chemistry laboratory 4.4.1. Main publications 4.4.2. Other publications 4.4.3. Patents 4.4.4. PhD completed 4.4.5. Grants and funds 4.4.6. Participations and invitations to congresses, seminars and research agencies 4.5. Clinical, Forensic, Environmental and Industrial, Toxicology laboratory 4.5.1. Main publications 4.5.2. Other publications Confidential -­‐ 2 CIRM Activity Report 2016 4.5.3. Patents 4.5.4. PhD completed 4.5.5. Grants and funds 4.5.6. Participations and invitations to congresses, seminars and research agencies 4.6. Clinical Microbiology laboratory 4.6.1. Main publications 4.6.2. Other publications 4.6.3. Patents 4.6.4. PhD completed 4.6.5. Grants and funds 4.6.6. Participations and invitations to congresses, seminars and research agencies 4.7. Clinical Pharmacology laboratory 4.7.1. Main publications 4.7.2. Other publications 4.7.3. Patents 4.7.4. PhD completed 4.7.5. Grants and funds 4.7.6. Participations and invitations to congresses, seminars and research agencies 4.8. Hospital and Clinical Pharmacology Unit 4.8.1. Main publications 4.8.2. Other publications 4.8.3. Patents 4.8.4. PhD completed 4.8.5. Grants and funds 4.8.6. Participations and invitations to congresses, seminars and research agencies 4.9. Quality Assurance Unit 4.9.1. Main events 4.10. Pharmaceutical Chemistry laboratory (LCP) 4.10.1. Main publications 4.10.2. Other publications 4.10.3. Patents 4.10.4. PhD completed 4.10.5. Grants and funds 4.10.6. Participations and invitations to congresses, seminars and research agencies 4.11. Pharmaceutical Technology and Biopharmacy laboratory (LTBP) 4.11.1. Main publications 4.11.2. Other publications 4.12.3. Patents 4.13.4. PhD completed 4.14.5. Grants and funds 4.15.6. Participations and invitations to congresses, seminars and research agencies 4.12. Pharmacognosy laboratory (LPG) 4.12.1. Main publications 4.12.2. Other publications 4.12.3. Patents 4.12.4. PhD completed 4.12.5. Grants and funds 4.12.6. Participations and invitations to congresses, seminars and research agencies 4.13. Tumors and Development Biology laboratory (LBTD) 4.13.1. Main publications 4.13.2. Other publications 4.13.3. Patents 4.13.4. PhD completed 4.13.5. Grants and funds 4.13.6. Participations and invitations to congresses, seminars and research agencies 4.14. Biological and Industrial Chemistry laboratory 4.14.1. Main publications 4.14.2. Other publications 4.14.3. Patents 4.14.4. PhD completed 4.14.5. Grants and funds 4.14.6. Participations and invitations to congresses, seminars and research agencies 4.15. Oxygen Biochemistry Group Confidential -­‐ 3 CIRM Activity Report 2016 4.15.1. Main publications 4.15.2. Other publications 4.15.3. Patents 4.15.4. PhD completed 4.15.5. Grants and funds 4.16.6. Participations and invitations to congresses, seminars and research agencies 5.
Communications within the CIRM 6.
CIRM technological platforms to support research Confidential -­‐ 4 CIRM Activity Report 2016 1. INTRODUCTION The Center for Interdisciplinary Research on Medicines (CIRM) has been restructured in 2015 due to the reorganization within the University of Liège that leads to separate structures for teaching and research activities. The general objective of the CIRM is to develop and maintain cutting-­‐edge research, fundamental and/or applied in the field of drugs. CIRM members are dealing with both research and teaching, and for some of them, clinical responsibilities. The combination of these three main activities was judged very fruitful and carrying interesting developments for all drug research aspects. The members of the CIRM join their forces to form a multidisciplinary Research Unit where all major aspects of the drug conception are covered. The research activities range from the discovery of new drug targets and the design or identification of lead compounds to their formulation and testing using all modern means of evaluation. The approaches use in vitro (membranes and cells) and in vivo pre-­‐clinical models (small animals), modern analytical tools but also innovative metabolomics and proteomics approaches. Patients-­‐oriented research is focused on the pharmacokinetics, clinical biology, toxicology, microbiology, pharmaceutical care and personalized medicine. Those research activities are undertaken in laboratories under Quality Assurance systems related to their activities (i.e. Active Pharmaceutical Ingredient (API) characterization, drug quality control, clinical trials, clinical biology assays…). The setting up of the CIRM is intended to increase the external visibility of the research activities, and to increase the autonomy to adapt the resources to research priorities and needs. Research excellence conducted at the CIRM must ensure the publications in well-­‐recognized international journals, the training of young researchers, the dissemination of knowledge to the scientific community and must offer expertise for the authorities of public health and/or pharmaceutical, chemical and biotechnologies industries, as well as for clinical perspectives. Confidential -­‐ 5 CIRM Activity Report 2016 2. CIRM 2.1 Introduction Around 240 people are presently working in the CIRM, including 135 researchers. The CIRM members are located on three Campus of the University; two located in Sart-­‐Tilman next to the CHU hospital and one in Gembloux. Fifteen laboratories belong to the CIRM, thirteen from the Faculty of Medicine, one from Veterinary Medicine and one from Gembloux Agro-­‐Biotech. 2.2 Current composition of the CIRM laboratories 2.2.1. Analysis of Medicines laboratory (LAM; 18 people) Head (1) Marianne Fillet Permanent senior scientists (2) Anne-­‐Catherine Servais, Jacques Crommen Post-­‐doctoral Researchers (2) Virginie Houbart, Miranda Kok PhD students (9) Aurore Napp, Alice Demelenne, Elena Farcas, Virginie Betonville, Radu Moldovan, Hanène Oueslati, Yang Huang, Gwenael Nys, Laurent Nyssen Technicians (3) Vincent Hurlet, Naima Boussif, Gael Cobraiville Secretary (1) Berangère Renaville 2.2.2. Analytical Chemistry laboratory (LCA; 21 people) Head (1) Philippe Hubert Permanent senior scientist (2) Robert Lejeune, Eric Ziemons Post-­‐doctoral Researchers (4) Charlotte Debleye, Amandine Dispas, Pierre-­‐Yves Sacré, Cédric Hubert PhD students (8) Lauranne Netchacovitch, Elodie Dumont, Hermane Avohou, Johan Cailletaud, Matthieu Clavaud, Bertyl Andri, Védaste Habyalimana, Nicodème Kalenda Technician (5) Sabah Houari, Sébastien Lhoest, Benoît Dahmen, Mélaine Gerday, Mélanie Heptia Secretary (1) Confidential -­‐ 6 CIRM Activity Report 2016 Florence Bonivert 2.2.3. ATC-­‐Pharma (ATC -­‐ PCA unit; 8 people) Head (1) Patrice Chiap Permanent senior scientist (4) Jean-­‐Claude Van Heugen, Thomas Dubrowski, Isabelle Leroy, Enza Arancio Post-­‐doctoral Researchers (0) / PhD students (0) / Technicians (3) Débora Lacroix, Enza Arancio, Laurence Levert Secretary (0) / 2.2.4. Clinical Chemistry laboratory (45 people) Head (1) : Etienne Cavalier Permanent senior scientist (3) : Romy Gadisseur, Caroline Le Goff, Laurence Lutteri Post-­‐doctoral Researchers (1): Neus Fabregat Cabello PhD students (2): Vincent Castiglione, Laurent Nyssen Technician (35): Marie-­‐Claire Aldenhoff, Mélissa Azzolina, Anne-­‐Catherine Bekaert, Catherine Benveniste, Kevin Blanco Valle, Eric Brevers, Cynthia Caracalla, Ignazia Carlisi, Mélanie Claessens, Grégory Collard, Réginald Demollin, Nunzio Ferrante, Séverine Geboes, Anne-­‐Sophie Gendebien, Adeline Heynen, Stéphanie Heynen, Loreen Huyghebaert, Stéphanie Kovacs, Stéphanie Jacob, Elizabeth Lafontaine, Martine Lastelle, Lorquet Aurore, Pierre Lukas, Giuseppe Musso, Cléo Nix, Stéphanie Peeters, Martine Pesser, Edwina Piazza, Marie-­‐
Louise Querinjean, Olivier Rousselle, Georges Spronck, Aurore Van Michel Dit Valet, Nicole Vangeebergen, Florence Watar, Pascale Watrin. Secretary (3): Fabienne Garro, Estelle Hennuy, Delphine Jeanne 2.2.5. Clinical, Forensic, Environmental and Industrial, Toxicology laboratory (20 people) Head (1) Corinne Charlier Permanent senior scientist (5) Raphaël Denooz, Marine Deville, Nathalie Dubois, Virgnie Mistretta, Catherine Pirard Post-­‐doctoral Researchers (0) PhD students (1) Confidential -­‐ 7 CIRM Activity Report 2016 Patrice Dufour Technician (11) Resmi Agirman, Alexandra Cordonnier, Jessica Deleersnyder, Delphine Delhotte, Nicolas Diet, Vanessa Ettari, Laurence Gerombous, Patricia Lanteir, Vivianne Malherbe, Isabelle Monet, Jennifer Pirotte. Secretary (2) Bernadette Cornet, Shirley Parent. 2.2.6. Clinical Microbiology laboratory (27 people) Heads (5): Pierrette Melin, Marie-­‐Pierre Hayette, Julie Descy, Pascale Huynen, Cécile Meex Permanent senior scientist (3): Sébastien Bontems, Rosalie Sacheli, Dolores Vaira Post-­‐doctoral Researchers: / PhD students (5): Eric Kamangu, Dieudonné Mvumbi, Imen Aouini, Elisa Solano (2016-­‐2017), Jean-­‐Claude Uwimbabazi (> 10.2016) Technician (13): Christine Art, Raphaël Boreux, Bernadette Spirlet, Laurent Lambert, Akolé Adjetey Bahun, Rajae Darfouf, Marie-­‐
Christine Duquesne, Chantal Henry, Giuseppina Oliveri, Adèle Puglisi, Fabrice Susin, Audrey Dupont, Marie Wery Secretary (1): Marie Christine Lhote 2.2.7. Clinical Pharmacology laboratory Head André Scheen 2.2.8. Hospital and Clinical Pharmacology Unit Head Thierry Van Hess Permanent senior scientist (3) Xavier Gerard, Manon Gillet, Audrey Samalea Suares, Post-­‐doctoral Researchers NA PhD students (3) Sophie Demarche, Christelle Vercheval, Fanny Dubois Technician NA Confidential -­‐ 8 CIRM Activity Report 2016 Secretary (1) Françoise Renard 2.2.9. Quality Assurance Unit (2 people) Permanent senior scientist (1) Joelle Widart Post-­‐doctoral Researchers (1) Roland Marini 2.2.10. Pharmaceutical Chemistry laboratory (LCP; 19 people) Head (1) Bernard Pirotte Permanent senior scientists (4) Pascal de Tullio, Pierre Francotte, Julien Hanson, Jean-­‐François Liégeois Post-­‐doctoral Researchers (3) Dayana ABBOUD, Alexandra Manos-­‐Turvey, Arvind Soni PhD students (6) Deniz Arslan, Thomas Drapier, Nadine Dupuis, Celine Laschet, Justine Leenders, Matthieu Schoumacher Researchers (2) Apostolos Felekidis, Eric Goffin Technician (2) Stéphane Counerotte, Nathalie Lefin Secretary (1) Sabine Houten 2.2.11. Pharmaceutical Technology and Biopharmacy laboratory (LTPB; 16 people) Head (1): Brigitte Evrard Permanent senior scientist (1): Géraldine Piel Post-­‐doctoral Researchers (3): Martine Cao, Claudio Palazzo, Justine Thiry PhD students (6): Coralie Bellefroid, William Bigazzi, Reatul Karim, Aude Pestiau, Hope Sounouvou Researchers (2): Charline Defourny, Aline Leballue, Olivier Jennotte Technicians (2): Laurence Collard, Françoise Léonard Confidential -­‐ 9 CIRM Activity Report 2016 Secretary (1): Annabelle Hamande 2.2.12. Pharmacognosy laboratory (LPG; 17 people) Head (1) Michel Frédérich Post-­‐doctoral Researchers (3) Ewa Cieckiewicz, Olivia Jansen, Alembert Tchinda PhD students (10) Allison Ledoux, Annélise Bordignon, Pascal Tshisekedi, Paulin Mutwale, Irina Ielciu, Don Jethro Mavungu, Védaste Kagisha, Aman Paul, Keshika Mahadeo, Sylvain Alson. Technicians (2) Delphine Etienne, Myriam Alorchi Secretary (1) Berangère Renaville 2.2.13. Tumors and Development Biology laboratory (LBTD; 52 people) Heads (2) Agnès Noel, Didier Cataldo Permanent senior scientist (6) C. Gilles, V. Lambert, E. Maquoi, C. Munaut, C. Péqueux, N.E. Sounni Post-­‐doctoral Researchers (9) S. Blacher, O. Carnet, M. Fransolet, M. Kasabova, J. Lecomte, N. Leroi, F. Morfoisse, N. Rocks, E. Tskitishvili PhD students (25) M. Bellefroid, G. Bendavid, I. Bourgot, A. Canale, K. Donati, C. Dubois, T. Durré, A. Duyckaerts, M. Ebroin, P. Foidart, ME. Francart, A. Gallez, C. Gérard, A. Goidfroid, C. Hubeau, F. Lallemand, J. Lambert, M. Lienard, G. Luis, L. Noel, I. Primac, C. Sépult, M. Van de Velde, A. Vanwynsberghe, C. Yip Technician (8) I. Dasoul, E. Feyereisen, C. Fink, P. Heneaux, E. Konradowski, N. Lefin, F. Perin, C. Vanwinge Secretary (2) H. Brisy, K. Van de Walle 2.2.14. Biological and Industrial Chemistry laboratory (CBI; 22 people) Head (1) Aurore Richel Permanent senior scientist (1) Nicolas Jacquet Post-­‐doctoral Researchers (1) Mario Aguedo Confidential -­‐ 10 CIRM Activity Report 2016 PhD students (13) Guillaume Maniet, Nicolas Villani, Thomas Berchem, Quentin Schmetz, Thibaut Istasse, Pierre-­‐Louis Bombeck, Brieuc Lecart, Glenn Bousfield, Thibault Nicodème, Li Qui, Krystian Miazek, Antoine Hospied, Maroua Kammoun Technician (6) Eric Groignet, Isabelle Vandervreke, Alexandre Schandeler, Catherine Chemotti, Virginie Byttebier, Frederic Meyer Secretary (0) / 2.2.15. Oxygen Biochemistry Group (CORD; 9 people) Head (1) Serteyn Didier Permanent senior scientist (1) Mouithys-­‐Mickalad Ange Post-­‐doctoral Researchers (2) Frnack Thierry, Ceusters Justine PhD students (4) Graide Hélène, Mendoza Luis, Bloomaert Didier, Nyssen Pauline (in collaboration with biomedical spectroscopy) Technician (1) Niesten Ariane Secretary (0) / Confidential -­‐ 11 CIRM Activity Report 2016 3. RESEARCH HIGHLIGHTS FROM THE CIRM
3.1. Introduction to the unifying thematics All laboratories of CIRM are encouraged to contribute and participate to intra-­‐CIRM interdisciplinary research projects, that we named unifying research thematics. Four main thematics answering to actual pharmaceutical and clinical needs have been identified offering the opportunity to bring together the skills of CIRM entities. Those challenging research fields concern: -­‐
Target and lead discovery: from the discovery and the validation of new drug targets to the synthesis or extraction of novel pharmacologically active small molecules, development of biologics, their characterization, quality control, formulation and in vitro testing. -­‐
Biopharmaceutics: towards a better biodisponibility of already commercialized drugs, focusing on BCS2 and BCS4 drugs, proteins, siRNA, and a better quality control of biopharmaceuticals, including virus like-­‐particles (vaccines). -­‐
Nanomedicine: targeted drug-­‐delivery systems using liposomes and other nanoparticules: from formulation and characterization to in vitro and in vivo testing, quality controls, pharmacokinetic and toxicological studies. -­‐
Personalized medicine: towards personalized pharmaceutical care, better diagnostic, prognostic and patient follow-­‐up. Confidential -­‐ 12 CIRM Activity Report 2016 4. SCIENTIFIC ACTIVITIES IN THE CIRM LABORATORIES In this section of the report, the scientific activities of the 15 laboratories of the CIRM are presented. For 2016, the complete list of publications, the patents obtained, the PhD theses completed, the grants obtained, and the participations and invitations to congresses and seminars are provided. The list of publications is divided into two parts. The first part mentions the publications for which the main part of the work has been performed by the CIRM laboratory (these publications are of major importance in the context of the evaluation). The second part provides the other publications. 4.1. Analysis of Medicines laboratory 4.1.1. Main publications Servais AC, Janicot B, Takam A, Crommen J, Fillet M. Liquid chromatography separation of the chiral prodrug eslicarbazepine acetate and its main metabolites in polar organic mode. Application to their analysis after in vitro metabolism. J. Chrom. A 2016, 1467:400-­‐408. Prior A, Moldovan RC, Crommen J, Servais AC, Fillet M, de Jong GJ, Somsen GW. Enantioselective capillary electrophoresis-­‐mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant. Anal Chim Acta. 2016 Oct 12; 940:150-­‐8. Doi: 10.1016/j.aca.2016.08.040. De Seny D, Cobraiville G, Leprince P, Fillet M, Collin C, Mathieu M, Hauzeur JP, Gangji V, Malaise MG Biomarkers of inflammation and innate immunity in atrophic nonunion fracture. J Transl Med. 2016 Sep 6;14:258. doi: 10.1186/s12967-­‐
016-­‐1019-­‐1. Denamur S, Boland L, Beyaert M, Verstraeten SL, Fillet M, Tulkens PM, Bontemps F, Mingeot-­‐Leclercq MP Subcellular mechanisms involved in apoptosis induced by aminoglycoside antibiotics: Insights on p53, proteasome and endoplasmic reticulum. Toxicol Appl Pharmacol. 2016 Oct 15;309:24-­‐36. doi: 10.1016/j.taap.2016.08.020 Moldovan RC, Bodoki E, Kacsó T, Servais AC, Crommen J, Oprean R, Fillet M. A micellar electrokinetic chromatography-­‐mass spectrometry approach using in-­‐capillary diastereomeric derivatization for fully automatized chiral analysis of amino acids. J Chromatogr A. 2016 Oct 7;1467:400-­‐408. doi: 10.1016/j.chroma.2016.08.035. Servais AC, Janicot B, Takam A, Crommen J, Fillet M. Liquid chromatography separation of the chiral prodrug eslicarbazepine acetate and its main metabolites in polar organic mode. Application to their analysis after in vitro metabolism. J Chromatogr A. 2016 Oct 7; 1467:306-­‐311. doi: 10.1016/j.chroma.2016.07.022. Furst T, Bettonville V, Farcas E, Frere A, Lechanteur A, Evrard B, Fillet M, Piel G, Servais AC. Capillary electrophoresis method to determine siRNA complexation with cationic liposomes. Electrophoresis. 2016 Oct; 37(20):2685-­‐2691. Doi: 10.1002/elps.201600249. Frédérich M, Pirotte B, Fillet M, de Tullio P. Metabolomics as a Challenging Approach for Medicinal Chemistry and Personalized Medicine. J Med Chem. 2016 Oct 13; 59(19):8649-­‐8666. Van der Vorm LN, Hendriks JC, Laarakkers CM, Klaver S, Armitage AE, Bamberg A, Geurts-­‐Moespot AJ, Girelli D, Herkert M, Itkonen O, Konrad RJ, Tomosugi N, Westerman M, Bansal SS, Campostrini N, Drakesmith H, Fillet M, Olbina G, Pasricha SR, Pitts KR, Sloan JH, Tagliaro F, Weykamp CW, Swinkels DW. Toward Worldwide Hepcidin Assay Harmonization: Identification of a Commutable Secondary Reference Material. Clin Chem. 2016 Jul;62(7):993-­‐1001. doi: 10.1373/clinchem.2016.256768. Houbart V, Cobraiville G, Nys G, Merville MP, Fillet M. Impact of injection solvent composition on protein identification in column-­‐switching chip-­‐liquid chromatography/mass spectrometry. J Chromatogr A. 2016 May 6;1445:27-­‐35. doi: 10.1016/j.chroma.2016.03.056. Guo J, Xiao Y, Lin Y, Crommen J, Jiang Z. Effect of the crosslinker type on the enantioseparation performance of β-­‐cyclodextrin functionalized monoliths prepared by the one-­‐pot approach. J Chromatogr A. 2016 Oct 7;1467:288-­‐296. doi: 10.1016/j.chroma.2016.05.078. Guo J, Lin Y, Xiao Y, Crommen J, Jiang Z. Recent developments in cyclodextrin functionalized monolithic columns for the enantioseparation of chiral drugs. J Pharm Biomed Anal. 2016 Oct 25;130:110-­‐125. doi: 10.1016/j.jpba.2016.05.023. Wang Q, Zhu P, Ruan M, Wu H, Peng K, Han H, Somsen GW, Crommen J, Jiang Z. Chiral separation of acidic compounds using an O-­‐9-­‐(tert-­‐
butylcarbamoyl)quinidine functionalized monolith in micro-­‐liquid chromatography. J Chromatogr A. 2016 Apr 29;1444:64-­‐73. doi: 10.1016/j.chroma.2016.03.047. Confidential -­‐ 13 CIRM Activity Report 2016 Guo J, Xiao Y, Lin Y, Zhang Q, Chang Y, Crommen J, Jiang Z. Influence of the linking spacer length and type on the enantioseparation ability of β-­‐cyclodextrin functionalized monoliths. Talanta. 2016 May 15;152:259-­‐68. doi: 10.1016/j.talanta.2016.02.016. Huang Y, Zhang T, Zhou H, Feng Y, Fan C, Chen W, Crommen J, Jiang Z. Fast separation of triterpenoid saponins using supercritical fluid chromatography coupled with single quadrupole mass spectrometry. J Pharm Biomed Anal. 2016 Mar 20;121:22-­‐9. doi: 10.1016/j.jpba.2015.12.056. Wu H, Wang Q, Ruan M, Peng K, Zhu P, Crommen J, Han H, Jiang Z. Enantioseparation of N-­‐derivatized amino acids by micro-­‐liquid chromatography/laser induced fluorescence detection using quinidine-­‐based monolithic columns. J Pharm Biomed Anal. 2016 Mar 20;121:244-­‐52. doi: 10.1016/j.jpba.2015.12.011. Wang Q, Sánchez-­‐López E, Han H, Wu H, Zhu P, Crommen J, Marina ML, Jiang Z. Separation of N-­‐derivatized di-­‐ and tri-­‐peptide stereoisomers by micro-­‐liquid chromatography using a quinidine-­‐based monolithic column -­‐ Analysis of l-­‐
carnosine in dietary supplements. J Chromatogr A. 2016 Jan 8;1428:176-­‐84. doi: 10.1016/j.chroma.2015.09.016. Lamalle C, Servais AC, Demelenne A, Crommen J, Fillet M. Analysis of protamine peptides in insulin pharmaceutical formulations by capillary electrophoresis. J Sep Sci. 2016 Mar;39(6):1189-­‐94. doi: 10.1002/jssc.201501093. Bettonville V, Nicol JT, Thelen N, Thiry M, Fillet M, Jacobs N, Servais AC. Study of intact virus-­‐like particles of human papillomavirus by capillary electrophoresis. Electrophoresis. 2016 Feb;37(4):579-­‐86. doi: 10.1002/elps.201500431. Farcaş E, Servais AC, Lamalle C, Chiap P, Pochet L, Fillet M. Fully automated electrophoretically mediated microanalysis for CYP1A1 activity monitoring optimized by multivariate approach. Electrophoresis. 2016 Jan;37(2):248-­‐55. doi: 10.1002/elps.201500214. 4.1.2. Other publications / 4.1.3. Patents / 4.1.4. PhD completed / 4.1.5. Grants and funds Crédit classique ULg (M. Fillet) (2016-­‐2017) Développement de méthodes de criblage de fragments et de mesure d’activité in vitro du FXIIa pour la découverte de nouveaux antithrombotiques. FSR 2016 Crédit Sectoriel de Recherche en Sciences de la Santé (M. Fillet) (2016-­‐2018) Capillary electrophoresis for drug screening,Bioanalytical assays and biomolecular interaction studies CDR -­‐ FNRS (M. Fillet) (2017-­‐2018) Microfluidc bioassays Crédit équipement FNRS (M. Fillet, P. de Tullio, B. Pirotte, M. Frederich) (2017-­‐2018) Mise à niveau électronique de la plateforme LC-­‐SPE-­‐
RMN du département de Pharmacie de l’ULg FEDER PHARE (M. Fillet), convention en cours, (2017-­‐
2021) Fonds Léon Frédéricq (G. Nys) (2016-­‐2017) Microfluidic LC-­‐MS validation of V65 vitronectin fragment, complement C3f and CTAPIII peptides as biomarkers of osteoarthritis severity. Fonds Léon Frédéricq (V. Houbart) (2016-­‐2017) Stratégies analytiques d’utilisation de l’alpha-­‐synucléine comme biomarqueur de la maladie de Parkinson. 4.1.6. Participations and invitations to congresses, seminars and research agencies V. Houbart, A. Napp, S. Rudaz, J. Schappler, M. Fillet. Alpha-­‐synuclein as biomarker in Parkinson’s disease: strategies for detection in CGE-­‐LIF. sd
32 International Symposium on Microscale Bioseparations (MSB), April 3-­‐7, 2016, Niagara-­‐on-­‐the-­‐
Lake, Canada (Communication orale + poster). M. Fillet Discovery and quantification of new biomarkers for preventive and predictive medicine. CIRM seminars, 19 May 2016, Liège, Belgium (communication orale). A Napp, V. Houbart, A.-­‐C. Servais, M.-­‐P. Merville, G. Garraux, M. Fillet. Analytical Challenges for the determination of alpha-­‐
synuclein and its oligomeric forms in the context of Parkinson disease. Confidential -­‐ 14 CIRM Activity Report 2016 CIRM seminars, 19 May 2016, Liège, Belgium (communication orale). R.C. Moldovan, E. Bodoki, T. Kacso, A-­‐C. Servais, J. Crommen, R. Oprean, M. Fillet. A New CE-­‐MS Approach Using In-­‐Capillary Derivatization for the Chiral Analysis of Amino Acids. 16th CEEPUS Symposium and Summer School on Bioanalysis, July 7-­‐10, 2016, Warsaw, Poland (Oral presentation). R. Chira, E. Bodoki, R.C. Moldovan, M. Fillet, R. Oprean Study of the Oxidative Metabolic Pathway of beta-­‐
blockers by Capillary Electrophoresis Coupled with Mass Spectrometry. 16th CEEPUS Symposium and Summer School on Bioanalysis, July 7-­‐10, 2016, Warsaw, Poland (Oral presentation). V. Bettonville, J. Nicol, N. Thelen, M. Thiry, M. Fillet, N. Jacobs, A.-­‐C. Servais. Stratégies pour l’identification et la quantification de pseudo-­‐particules virales de papillomavirus humain par électrophorèse capillaire. èmes
9 journées scientifiques de l’AFIPP, September 28-­‐30, 2016, Loches, France (communication orale). E. Farcaş, A.-­‐C. Servais, C. Lamalle, L.-­‐G. Manica, P. Chiap, L. Pochet, M. Fillet. Optimization of a fully automated electrophoretically mediated microanalysis system for CYP1A1 activity monitoring. th
The 16 Edition of National Congress of Pharmacy in st
Romania, September 28 -­‐ October 1 , 2016, Bucharest, Romania. (Communication orale). G. Nys, A-­‐C. Servais, C. Pequeux, M. Fillet. Pharmacokinetic study of estetrol in murin model developing a whole blood microsampling, extraction procedure and an UHPLC-­‐MS/MS method. th
19 forum of pharmaceutical sciences, October 17-­‐18 2016, Bruxelles, Belgium (communication orale). A Demelenne, A. Napp, A-­‐C. Servais, M. Fillet. Study of insulin aggregation by SEC and CGE. th
19 Forum of Pharmaceutical Sciences, October 17-­‐18, 2016, Brussels, Belgium (Short 1-­‐slide Communication). L. Nyssen, E. Cavalier, M. Fillet, A.-­‐C. Servais. Innovative approach using sheathless CE-­‐MS/MS for the quantitation of parathormone in native form. th
19 Forum of Pharmaceutical Sciences, October 17-­‐18, 2016, Brussels, Belgium (communication orale). Electrodriven separation systems for bioassay-­‐guided development of antithrombotic agents. th
27 International Symposium on Pharmaceutical and Biomedical Analysis (PBA), November 13-­‐16, 2016, Guangzhou, China (communication orale). Y. Huang, J. Crommen, Z.J. Jiang. Fast separation of triterpenoid saponins using supercritical fluid chromatography coupled with single quadrupole mass spectrometry. th
18 International Symposium on Advances in Extraction th
Technologies & 22 International Symposium on Separation Sciences, July 3-­‐6, 2016, Torun, Poland, p147: S1-­‐P42.(Poster) Y. Huang, T.T. Zhang, Y.M. Zhao, H.B. Zhou, G.Y. Tang, M. Fillet, J. Crommen, Z.J. Jiang. Simultaneous analysis of nucleobases, nucleosides and ginsenosides in ginseng extracts using supercritical fluid chromatography coupled with single quadrupole mass spectrometry. th
27 International Symposium on Pharmaceutical and Biomedical Analysis, November 13-­‐16, 2016, Guangzhou, China.p304: S2-­‐P36 (Poster). Y. Huang, M. Fillet, J. Crommen, Z.J. Jiang, Determination of saccharides in honey using supercritical fluid chromatography coupled with single quadrupole mass spectrometry. th
27 International Symposium on Pharmaceutical and Biomedical Analysis, November 13-­‐16, 2016, Guangzhou, China. p300: S2-­‐P32 (Poster). V. Bettonville, J.T. Nicol, N. Thelen, M. Thiry, M. Fillet, N. Jacobs, A.-­‐C. Servais. Quantitation and biospecific identification of virus-­‐like particles of human papillomavirus using capillary electrophoresis. th
27 International Symposium on Pharmaceutical and Biomedical Analysis (PBA), November 13-­‐16, 2016, Guangzhou, China (Communication orale sur invitation). M. Fillet. Optimisation of analytical methods. In the framework of High-­‐end Foreign Experts program, Jinan University, College of Pharmacy. November 21, 2016, Guangzhou, China (communication orale). E. Farcas, C. Bouckaert, A-­‐C. Servais, Y. Zhao, Z. Jiang, J. Crommen, L. Pochet, M. Fillet. Confidential -­‐ 15 CIRM Activity Report 2016 4.2. Analytical Chemistry laboratory 4.2.1. Main publications Dispas A., Lebrun P., Sacre P.-­‐Y., & Hubert Ph. Screening study of SFC critical method parameters for the determination of pharmaceutical compounds. J. Pharm. & Biomed. Anal (2016), 125: 339-­‐354. Andri B., Dispas A., Marini Djang'Eing'A R., & Hubert Ph. Overview of the Analytical Lifecycle of Supercritical Fluid Chromatography Methods. AJAC (2016), 7: 75-­‐91. Thiry J., Lebrun P., Vinassa C., Adam M., Netchacovitch, L., Ziemons, E., Hubert, Ph., Krier F., & Evrard B. Continuous Production of Itraconazole-­‐based Solid Dispersions by Hot Melt Extrusion: Preformulation, Optimization and Design Space Determination. Int. J. Pharm. (2016), 515: 114-­‐124. De Bleye C., Dumont E., Dispas A., Hubert C., Sacre P.-­‐
Y., Netchacovitch L., De Muyt B., Kevers C., Dommes J., Hubert Ph. & Ziemons E. Monitoring of anatabine release by methyl jasmonate elicited BY-­‐2 cells using surface-­‐enhanced Raman scattering. Talanta (2016), 160: 754-­‐760. Netchacovitch L., Thiry J., De Bleye C., Dumont E., Dispas A., Hubert C., Krier F., Sacre P.-­‐Y., Evrard B., Hubert Ph., & Ziemons E. A simple calibration approach based on film-­‐casting for confocal Raman microscopy to support the development of a Hot-­‐Melt Extrusion process. Talanta (2016), 154: 392-­‐399. Dumont E., De Bleye C., Sacre P.-­‐Y., Netchacovitch L., Hubert Ph., & Ziemons E. From Near-­‐Infrared and Raman to Surface-­‐Enhanced Raman Spectroscopy: Progress, Limitations, Perspectives in Bioanalysis. Bioanalysis (2016), 8: 1077-­‐1103. Clavaud M., Roggo Y., Dégardin K., Sacre P.-­‐Y., Hubert Ph, & Ziemons E. Moisture content determination in an antibody-­‐drug conjugate freeze-­‐dried medicine by near-­‐infrared spectroscopy: a case study for release testing. J. Pharm. & Biomed. Anal (2016), 131: 380-­‐390. 4.2.2. Other publications Baldacci-­‐Cresp, F., Sacre P.-­‐Y., Twyffels L., Mol A., Vermeersch M., Ziemons E., Hubert Ph, Pérez-­‐Morga D., El Jarizi M., de Almeida-­‐Engler J., & Baucher M. Poplar-­‐root-­‐knot nematode interaction: a model for perennial woody species. Molecular Plant-­‐Microbe Interactions [=MPMI] (2016), 29: 560-­‐572. 4.2.3. Patents / 4.2.4. PhD completed DEBLEYE Charlotte Surface-­‐enhanced Ramanscattering on small molecules: Investigation of quantitative performances PhD in Biomedical and Pharmaceutical Sciences (2016) DISPAS Amandine Supercritical Fluid Chromatography for pharmaceutical analysis: New perspectives PhD in Biomedical and Pharmaceutical Sciences (2016) 4.2.5. Grants and funds FNRS “Aspirant Research Fellow” (2016-­‐2020) Development of SERS nanosensors for the detection of small bioactive molecules by cellular analysis in complex matrices Logistics in Wallonia (2016-­‐2019) Conception d’un “cloud” pour la détection de medicaments contrefaits par spectroscopie vibrationnelle Faculté de Médecine – Mandat d’élève-­‐chercheur (2016-­‐
2017) Développement de nanosenseurs pour la détection de petites molécules bioactives par imagerie cellulaire dans des matrices complexes 4.2.6. Participations and invitations to congresses, seminars and research agencies Chimiométrie XVII, Namur, Belgium, January 17-­‐20 2016. Eurachem International Workshop -­‐ Method Validation in Analytical Science -­‐ Current Practices and Future Challenges. Ghent, Belgium, May 10 2016. Journée thématique du Club IDF de l'AFSEP, Paris, France, January 21 2016. Congrès International de la pathologie infectieuse et parasitaire, Kinshasa, République Démocratique du Congo, Dember 14 2016. SFC 2016, Vienna, Austria, October 07 2016. International Symposium on Chromatography -­‐ ISC 2016, Cork, Ireland, August 30 2016. Chemometrics in Analytical Chemistry, Barcelona, Spain, June 6 2016. Raman Fest 2016, Berlin, Germany, May 19 2016. The Bioforum 2016 of BioLiège, Liège, Belgique, November 16 2016. 19th Forum of Pharmaceutical Sciences, Brussels, Belgium, October 18 2016. Confidential -­‐ 16 CIRM Activity Report 2016 4.3. ATC-­‐Pharma (ATC) 4.3.1. Main publications Farcas E., Servais A.-­‐C., Lamalle C., Chiap P., Pochet L. and Fillet M. Fully automated electrophoretically mediated microanalysis for CYP1A1 activity monitoring optimized by multivariate approach. Electrophoresis (2016), 37(2), 248-­‐255. 4.3.2. Other publications / 4.3.3. Patents / 4.3.4. PhD completed / 4.3.5. Grants and funds Several signed contracts with pharmaceutical companies (human and veterinary health). 4.3.6. Participations and invitations to congresses, seminars and research agencies Adebiotech – StressOx (modulation du stress oxydant). Romainville (Paris), France, May 31 -­‐ June 1, 2016. Confidential -­‐ 17 CIRM Activity Report 2016 4.4. Clinical Chemistry laboratory 4.4.1. Main publications Le Goff, C., Kaux, J.-­‐F., Laurent, T., Vannuscorps, J., Seidel, L., Rodriguez de la Cruz, C., Forthomme, B., Bury, T., Chapelle, J.-­‐P., Cavalier, E., & Croisier, J.-­‐L. (2016). The cardiovascular impact of intense eccentric isokinetic exercise versus aerobic treadmill running. Isokinetics & Exercise Science, 24(3), 201-­‐208. Cavalier, E., Bergmann, P., Bruyère, O., DELANAYE, P., Durnez, A., Devogelaer, J.-­‐P., Ferrari, S. L., Gielen, E., Goemaere, S.,Kaufman, J.-­‐M., Nzeusseu Toukap, A., Reginster, J.-­‐Y., ROUSSEAU, A.-­‐F., Rozenberg, S., Scheen, A., & Body, J.-­‐J. (2016). The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 27, 2181-­‐2195. DELANAYE, P., LE GOFF, C., JOURET, F., & CAVALIER, E. (2016). Concordance between Iothalamate and Iohexol Plasma Clearance [letter to the editor]. American Journal of Kidney Diseases, 68(2), 329-­‐330. Moreau, E., Bächer, S., Mery, S., Goff, C., Piga, N., Vogeser, M., Hausmann, M., & CAVALIER, E. (2016, January). Performance characteristics of the VIDAS 25-­‐OH Vitamin D total assay -­‐ comparison with four immunoassays and two liquid chromatography-­‐tandem mass spectrometry methods in a multicentric study. Clinical Chemistry & Laboratory Medicine. Bargnoux, A.-­‐S., Kuster, N., Delatour, V., DELANAYE, P., Gonzalez-­‐Antuna, A., Cristol, J.-­‐P., Piéroni, L., & CAVALIER, E. (2016). Reference Method and Reference Material Are Necessary Tools to Reveal the Variability of Cystatin C Assays [letter to the editor]. Archives of Pathology & Laboratory Medicine, 140(2), 117-­‐118. CAVALIER, E., LUKAS, P., BEKAERT, A.-­‐C., PEETERS, S., LE GOFF, C., Yayo, E., DELANAYE, P., & Souberbielle, J.-­‐C. (2016). Analytical and clinical evaluation of the new Fujirebio Lumipulse G non-­‐competitive assay for 25(OH)-­‐vitamin D and three Immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients. Clinical Chemistry & Laboratory Medicine. DELANAYE, P., JOURET, F., LE GOFF, C., & CAVALIER, E. (2016). Concordance between iohexol and iothalamate plasma clearance. American Journal of Kidney Diseases. Jean, G., Chazot, C., Bresson, E., Zaoui, E., & CAVALIER, E. (2016) High serum sclerostin levels are associated with a better outcome in haemodialysis patients. Nephron. Clinical Practice. Lutteri, L., Dierge, L., PESSER, M., WATRIN, P., & Cavalier, E. A paperless autoimmunity laboratory: myth or reality? Annales de Biologie Clinique, 74(4), 477-­‐89. ROUSSEAU, A.-­‐F., Damas, P., DELANAYE, P., & Cavalier, E. (2016) Bone markers during acute burn care: Relevance to clinical practice? Burns: Journal of the International Society for Burn Injuries. EVRARD, S., DELANAYE, P., Kamel, S., Cristol, J., & CAVALIER, E. (2015). Vascular calcification: from pathophysiology to biomarkers. Clinica Chimica Acta, 438, 401-­‐14. LE GOFF, C., Kaux, J.-­‐F., D'OTREPPE DE BOUVETTE, S., Goffaux, S., Fillet, M., Chapelle, J.-­‐P., & Cavalier, E. Release of cardiac biomarkers during a cycling race. World Journal of Cardiovascular Diseases, 6(8), 285-­‐294. Cavalier, E., Jandrain, B., Coffiner, M., Da Silva, S., De Niet, S., Vanderbist, F., & Souberbielle, J.-­‐C. A Randomised, Cross-­‐Over Study to Estimate the Influence of Food on the 25-­‐Hydroxyvitamin D(3) Serum Level after Vitamin D(3) Supplementation. Nutrients, 8(5). 4.4.2. Other publications Gonzalez Aguilera, B., Syrios, P., Gadisseur, R., LUYCKX, F., Cavalier, E., Beckers, A., & VALDES SOCIN, H. G. Persistent low levels of serum hCG due to heterophilic mouse antibodies: an unrecognized pitfall in the diagnosis of trophoblastic disease. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology, 1-­‐3 (2016) Beaudart, C., McCloskey, E., Bruyère, O., Cesari, M., Rolland, Y., Rizzoli, R., Araujo de Carvalho, I., Amuthavalli Thiyagarajan, J., Bautmans, I., Bertière, M.-­‐C., Brandi, M. L., Al-­‐Daghri, N. M., Burlet, N., CAVALIER, E., Cerreta, F., Cherubini, A., Fielding, R., Gielen, E., Landi, F., PETERMANS, J., Reginster, J.-­‐Y., Visser, M., Kanis, J., & Cooper, C. (2016). Sarcopenia in daily practice: assessment and management. BMC Geriatrics, 16(170). DELANAYE, P., Ebert, N., Melsom, T., Gaspari, F., Mariat, C., CAVALIER, E., Björk, J., Christensson, A., Nyman, U., Confidential -­‐ 18 CIRM Activity Report 2016 Porrini,E., Remuzzi, G., Ruggenenti, P., Schaeffner, E., Soveri, I., Sterner, G., Odvar Eriksen, B., & Bäck, S.-­‐E. (2016, October). Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol? Clinical Kidney Journal. DELANAYE, P., Melson, T., Ebert, N., Bäck, S.-­‐E., Mariat, C., CAVALIER, E., Björk, J., Christensson, A., Nyman, U., Porrini, Remuzzi, G., Ruggenenti, P., Schaeffner, E., Soveri, I., Sterner, G., Odvar Eriksen, B., & Gaspari, F. (2016, October). Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2: Why to measure glomerular filtration rate with iohexol? Clinical Kidney Journal. Van Houcke, S. K., Seaux, L., Cavalier, E., Speeckaert, M. M., Dumoulin, E., Lecocq, E., & Delanghe, J. R. (2016, September). Determination of iohexol and iothalamate in serum and urine by capillary electrophoresis. Electrophoresis. Ebert, N., DELANAYE, P., Shlipak, M., Jakob, O., Martus, P., Bartel, J., Gaedeke, J., van der Giet, M., Schuchardt, M., CAVALIER, E., & Schaeffner, E. (2016). Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate. Clinica Chimica Acta, 456, 115-­‐121. Souberbielle, Massart, C., Brailly-­‐Tabard, S., CAVALIER, E., & Chanson, P. (2016, April). Prevalence and determinants of vitamin D deficiency in healthy French adults: the VARIETE study. Endocrine. Kaux, J.-­‐F., Croisier, J.-­‐L., Forthomme, B., LE GOFF, C., Buhler, F., Savanier, B., DELCOUR, S., Gothot, A., & Crielaard, J.-­‐M. (2016). Using platelet-­‐rich plasma to treat jumper’s knees: Exploring the effect of a second closely-­‐timed infiltration. Journal of Science and Medicine in Sport, 19(3), 200-­‐204. Buckinx, F., Reginster, J.-­‐Y., Cavalier, E., PETERMANS, J., Ricour, C., Dardenne, C., & Bruyère, O. (2016). Determinants of vitamin D supplementation prescription in nursing homes: a survey among general practitioners. Osteoporosis International, 27, 881-­‐6. DELANAYE, P., CAVALIER, E., Fafin, C., DUBOIS, B., KRZESINSKI, J.-­‐M., & Moranne, O. (2016). Efficiency of delivery observed treatment in hemodialysis patients: the example of the native vitamin D therapy. Journal of Nephrology, 29(1), 99-­‐103. DELANAYE, P., Flamant, M., CAVALIER, E., Guerber, F., Valloton, T., Moranne, O., Pottel, H., Boffa, J., & Mariat, C. (2016). Adaptation posologique des médicaments et fonction rénale : Quel(s) estimateur(s) faut-­‐il choisir? Néphrologie & Thérapeutique, 12(1), 18-­‐31. Souberbielle, J., Massart, Brailly-­‐Tabard, S., Cormier, C., CAVALIER, E., DELANAYE, P., & Chanson, P. (2016). Serum PTH reference values established by an automated third-­‐generation assay in Vitamin D-­‐replete subjects with normal renal function: Consequences of diagnosing primary hyperparathyroidism and the classification of dialysis patients. European Journal of Endocrinology, 174(3), 315-­‐323. VALDES SOCIN, H. G., SID, S., LUTTERI, L., POLUS, M., Louis, E., Beguin, Y., & Beckers, A. (2016). Le syndrome thyrogastrique auto-­‐immun : actualités cliniques et thérapeutiques. Vaisseaux, Coeur, Poumons, 21(4), 11-­‐15. Sagou Yayo, E., Aye, E., Konan, J., Emième, A., Attoungbré, M., Gnionsahé, A., CAVALIER, E., Monnet, D., & DELANAYE, P. (2016). Inadéquation du facteur ethnique pour l’estimation du débit de filtration glomérulaire en population générale noireafricaine: résultats en Côte d’Ivoire. Néphrologie & Thérapeutique, 12(6), 454-­‐459. Le Goff, C., Gergelé, L., Kaux, J.-­‐F., Cavalier, E., & Millet, G. (2016). Impact of a mountain ultra-­‐marathon on cardiac biomarkers. Crossing borders through sport science (pp. 509). BERTHOLET, C., GADISSEUR, R., quinting, B., & courtois, J. (2016). ALERBLOT: Interest of 2D Immunoblot for the diagnosis of allergy to wheat. Allergy, 71. BERTHOLET, C., GADISSEUR, R., & Quinting, B. (2016). Mise au point d’une nouvelle méthode de diagnostic des allergènes du froment par Western blot 2D. Revue Française d'Allergologie, 56(3), 284. CAVALIER, E., CARLISI, I., KOVACS, S., WATAR, F., Beaudart, C., Buckinx, F., Bruyère, O., & Reginster, J.-­‐Y. (2016). Brainderived neurotrophic factor (BDNF) in normal healthy and hemodialyzed populations. Osteoporosis International, 27(Supplement 1), 512. CAVALIER, E., Piron, C., WATAR, F., KOVACS, S., Beaudart, C., Buckinx, F., Bruyère, O., LE GOFF, C., & Reginster, J.-­‐Y. (2016). Evaluation of the intra-­‐individual variability of myostatin and activin A, two biomarkers of sarcopenia: impact on the least significant change and followup of the patients. Osteoporosis International, 27(supplement 1), 56. CAVALIER, E., Carlisi, A. S., WATAR, F., KOVACS, S., Beaudart, C., Buckinx, F., Bruyère, O., & Reginster, J.-­‐Y. (2016). Confidential -­‐ 19 CIRM Activity Report 2016 Brain-­‐derived neurotrophic factor (BDNF) in normal healthy and hemodialyzed populations. Journal of Frailty & Aging, 5(Supplement 1), 116. CAVALIER, E., Piron, C., WATAR, F., KOVACS, S., Beaudart, C., Buckinx, F., Bruyère, O., LE GOFF, C., & Reginster, J.-­‐Y. (2016). Evaluation of the intra-­‐individual variability of myostatin and activin A, two biomarkers of sarcopenia. Impact of the least significant change and follow-­‐up of the patients. Journal of Frailty & Aging, 5(Supplement 1), 82. ROUSSEAU, A.-­‐F., Michel, L., Bawin, M., CAVALIER, E., Reginster, J.-­‐Y., DAMAS, P., & Bruyère, O. (2016). Incidence of bone fractures after critical illness. Intensive Care Medicine Experimental, 4(Suppl 1), 1131. Yayo, E., Monnet, D., Attoungbré, M.-­‐L., Gnionsahé, A., CAVALIER, E., Pottel, H., & DELANAYE, P. (2016). Valeurs de référence de débit de filtration glomérulaire en population noire-­‐africaine. Néphrologie & Thérapeutique, 12(5), 273. Kaux, J.-­‐F., CROISIER, J.-­‐L., FORTHOMME, B., Le Goff, C., Gothot, A., DELCOUR, S., & Crielaard, J.-­‐M. (2016). Exploring the effect of a second closely-­‐timed infiltration of platelet-­‐rich plasma to treat proximal patellar tendinopathies. European Journal of Physical and Rehabilitation Medicine, 54(Suppl. 1 No. 2), 199. Le Goff, C., Kaux, J.-­‐F., Cavalier, E., & Croisier, J.-­‐L. (2016). Is isokinetic exercise dangerous for the heart? European Journal of Physical and Rehabilitation Medicine, 52(suppl. 1 No. 2), 457. PAQUOT, F., BOUQUEGNEAU, A., CAVALIER, E., & DELANAYE, P. (2016). Sclérostine & insuffisance rénale: que nous apprennent les différents méthodes de dosage? Néphrologie & Thérapeutique, 12(5), 374. 4.4.3. Patents / 4.4.4. PhD completed / 4.4.5. Grants and funds / 4.4.6. Participations and invitations to congresses, seminars and research agencies World congress on osteoporosis, osteoarthritis ans musculoskeletal diseases, WCO-­‐IOF-­‐ESCEO, Malaga, Spain, April 14-­‐17, 2016. ICFSR 2016 in Philadelphia, USA April 28-­‐29, 2016 53rd ERA-­‐EDTA Congress in Vienna, Austria, May 21-­‐24, 2016. ASN, Kidney Week, Chicago, USA, November 17-­‐20, 2016. 4th International South Tyrolean Diagnostic Forum -­‐ Bolzano, December 1st -­‐ 2nd, 2016. 15/3 Colloque endocrinologie NDB Liege 16/4 Congres national de Pédiatrie, Wépion, Belgique 25/4/16 Congres ESPRM, Estoril, Portugal 28/4/16 Formation continue Biologie Clinique, Liege 8/7/16 ECSS, Vienne, Autriche 14/9/16 MSACL, Salzburg, Autriche 28/9/16, Corata, Strasbourg, France 14/10/16, SRBML, Val St Lambert, Liege, Belgique 01/11/16, SFMS, Agadir,Maroc 17/11/16, Glem, Liege, Belgique Séminaire LUNE (lithiase urinaire pour les néphrologues) : Calculs calcium-­‐dépendant: quels objectifs? -­‐ Hopital de la Pitié-­‐Salpétrière, Paris, 15 Janvier 2016
-­‐ 14èmes Journées de la Faculté de Médecine de l'ULg : Intérêt médical et économique de l'analyse morpho-­‐
constitutionnelle des calculs urinaires récidivants -­‐ CHU de Liège 22 mai 21e Confrontations clinico-­‐biologiques autour de la lithiase urinaire : Case report autour de cristalluries médicamenteuses atypiques -­‐ Hopital Tenon, Paris 14 octobre 15/12/16 Colloque de biologie clinique,LHUB-­‐ULB, Bruxelles, Belgique Confidential -­‐ 20 CIRM Activity Report 2016 4.5. Clinical, Forensic, Environmental and Industrial, Toxicology laboratory 4.5.1. Main publications P. Dufour, C. Pirard, C. Charlier, Validation of a novel and rapid method for the simultaneous determination of some phenolic organohalogens in human serum by GC–
MS, Journal of Chromatography B., 1036–1037 (2016) 66–75. Mistretta V, Charlier C, Les prothèses de hanche au cobalt sont-­‐elles dangereuses ? Médecine/Sciences, 2016, 32, 732-­‐738. C. Pirard, J-­‐M. Brouhon, A. Fourmeaux, C.Charlier, A simple tiered methodology for the determination of ambient air quality guidelines, Clean-­‐Soil, Air, Water, 2016, 44, 464-­‐473. E. Lemaire, C. Charlier, Ph. Boxho, Site-­‐, Technique-­‐ and time-­‐related aspects of the postmortem redistribution of drazepam, methadone, morphine and their metabolites : interest of popliteal vein blood sampling, Journal of Forensic Sciences, 2016. 4.5.2. Other publications I. Demaret, E. Quertemont, G. Litran, C. Magoga, C. Deblire, N. Dubois, C. Charlier, A. Lemaitre, M. Ansseau, Loss of treatment benefit when heroin-­‐assisted treatment is stopped after 12 months, Journal of Substance Abuse Treatment, 2016, 69, 72-­‐75 E. Lemaire, C. Schmidt, R. Denooz, C. Charlier, Ph. Boxho, Popliteal vein blood sampling and the post-­‐
mortem redistribution of diazepam, methadone and morphine, Journal of Forensic Sciences, 2016, Jul; 61 (4): 1017-­‐28 4.5.3. Patents / 4.5.4. PhD completed HAHIRWA Innocent, Therapeutic drug monitoring and detection of intoxications for psychotropic drugs used in Rwanda PhD in Pharmaceutical Sciences (2016). 4.5.5. Grants and funds / 4.5.6. Participations and invitations to congresses, seminars and research agencies « Effets à court et à long terme du cannabis et des cannabinoïdes de synthèse », Printemps des Sciences 2016, Liège, March 14, 2016. « Niveau actuel de contamination de la population ème
générale liégeoise par les pesticides », 46 congrès du GFP, Bordeaux, may 19, 2016. « Toxicomanies : nouvelles substances, nouveaux usages », Enseignement post-­‐universitaire en Ophtalmologie, Liège, May 23, 2016. « Le sabotage de notre système hormonal par les polluants de l’environnement », Conférences d’Endocrinologie de Soiron, Soiron, May 25, 2016. « Contamination des habitants de la Province de Liège par les perturbateurs endocriniens, ces Polluants capables de bouleverser notre équilibre hormonal », Service provincial de Promotion de la Santé, Liège, June 23, 2016. BLT week-­‐end Esternach, October 21-­‐22, 2016. “Strychnine poisoning still happens in 2015”, TIAFT 2016, Brisbane, Australia, August 28 – September 1, 2016. SFTA Congress, Perpignan, France, May 31 – June 3, 2016. International Conference on Heavy Metals in the Environment (ICHMET), Gent, September 12-­‐15, 2016. Confidential -­‐ 21 CIRM Activity Report 2016 4.6. Clinical Microbiology laboratory 4.6.1. Main publications Hayette M.P., Sacheli R. Unusal dermatophytes : rarely identified or new ? Mycopathologia, 2016, DOI 10.1007/s11046-­‐016-­‐0066-­‐8. Mvumbi D., Bobanga T. , Umesumbu S. , Kunyu , B. , Kayembe J.M., Situakibanza Nani-­‐Tuma H , Mvumbi G., Melin P. ,De Mol P , Hayette M.P. Investigation on possible transmission of monkeys' plasmodium to human in a populations living in the equatorial rainforest of the Democratic Republic of Congo. Int J Parasitol Parasites Wildl. 2015 Dec 2;5(1):1-­‐4. Mvumbi DM, Bobanga TL, Melin P, De Mol P,Kayembe JM, Situakibanza HN, Mvumbi GL, Nsibu CN, Umesumbu SE, Hayette MP. High Prevalence of Plasmodium falciparum Infection in Asymptomatic Individuals from the Democratic Republic of the Congo. Malar Res Treat. 2016:5405802. Sacheli R., Adjetey C., Darfouf R., Harag S., Huynen P., Meex C., Descy J., Melin P., Arrese J., Hayette P. P. A one-­‐year survey of Microsporum audouinii infections in Belgium: epidemiological and genotypic characterisation. CMI, 2016 Mar;22(3):285.e9-­‐17. Trouvé C, Blot S, Hayette MP, Jonckheere S, Patteet S, Rodriguez-­‐Villalobos H, Symoens F, Van Wijngaerden E, Lagrou K. Epidemiology and reporting of candidaemia in Belgium: a multi-­‐centre study. Eur J Clin Microbiol Infect Dis. 2016 Nov 17. [Epub ahead of print] Dauby, N., Chamekh, M., Melin, P., Slogrove, A. L., & Goetghebuer, T. (2016). Increased Risk of Group B Streptococcus Invasive Infection in HIV-­‐Exposed but Uninfected Infants: A Review of the Evidence and Possible Mechanisms. Frontiers in Immunology, 7, 505/1-­‐8. http://hdl.handle.net/2268/204513 da Silva Polo, T., Peiro, J., Claudio Nogueira Mendes, L., Ludwig, L., de Oliveira-­‐Filho, E., Bucardo, F., Huynen, P., Melin, P., Thiry, E., & Mauroy, A. (2016). Human norovirus infection in Latin America. Journal of Clinical Virology, 78, 111-­‐119. http://hdl.handle.net/2268/196571 4.6.2. Other publications Marta Maciejewska, Delphine Adam, Loïc Martinet, Aymeric Naômé, Magdalena Całusi´ nska, Philippe Delfosse, Monique Carnol, Hazel A. Barton, Marie-­‐Pierre Hayette, Nicolas Smargiasso, Edwin De Pauw, Marc Hanikenne, Denis Baurain and Sébastien Rigali. A Phenotypic and Genotypic Analysis of the Antimicrobial Potential of Cultivable Streptomyces Isolated from Cave Moonmilk Deposits. Frontiers in Microbiology, 2016. Darcis G, Hayette MP, Bontems S, Sauvage AS, Meuris C, Van Esbroeck M, Leonard P. Louse-­‐borne relapsing fever in a refugee from Somalia arriving in Belgium. J Travel Med. 2016 Mar; 23(3). Canton, R., Livermore, D. M., Morosini, M. I., Diaz-­‐
Reganon, J., Rossolini, G. M., Melin, P., & Premium Study Group, S. C. I. P. M. (2016, October 20). Etest® versus broth microdilution for ceftaroline MIC determination with Staphylococcus aureus: results from PREMIUM, a European multicentre study. Journal of Antimicrobial Chemotherapy. http://hdl.handle.net/2268/204515 Desmet, S., Verhagen, J., Glupczynski, Y., Van Eldere, J., Melin, P., Goossens, H., Pierard, D., Declercq, P., Lagrou, K., Boel, A., Cartuyvels, R., Denis, O., Vandewal, W., & Saegeman, V. (2016, May). Development of a national EUCAST challenge panel for antimicrobial susceptibility testing. Clinical Microbiology and Infection. http://hdl.handle.net/2268/197774 Brasseur, D., Rigo, J., Melin, P., Cossey, V., Daube, G., Goossens, L., Hennekin, Y., Huyghebaert, A., Johansson, A.-­‐B., Maton, P., & Witters, A. (2016). Recommandations relatives à l’usage de lait maternel cru pour les prématurés hospitalisés en Néonatologie -­‐ Administration du lait de la mère à son propre enfant -­‐ Avis 8734. Bruxelles, Belgique: Conseil Supérieur de la Santé. http://hdl.handle.net/2268/199614 Huynen P., Lazzarotto T., Peyron F. Toxoplasma gondii, cytomegalovirus, and Treponema pallidum infections in pregancy: what’s new? Wiener Klinisches Magazin 2016;1(3), 1-­‐8. Hofstra LM, Sauvageot N, Albert J, Alexiev I, Garcia F, Struck D, Van de Vijver DA, Åsjö B, Beshkov D, Coughlan S, Descamps D, Griskevicius A, Hamouda O, Horban A, Van Kasteren M, Kolupajeva T, Kostrikis LG, Liitsola K, Linka M, Mor O, Nielsen C, Otelea D, Paraskevis D, Paredes R, Poljak M, Puchhammer-­‐Stöckl E, Sönnerborg A, Staneková D, Stanojevic M, Van Laethem K, Zazzi M, Zidovec Lepej S, Boucher CA, Schmit JC, Wensing AM; SPREAD Program..(D.Vaira) Transmission of HIV Drug Resistance and the Predicted Effect on Current First-­‐line Regimens in Europe. Clin Infect Dis. 2016 Mar 1;62(5):655-­‐63. doi: 10.1093/cid/civ963 4.6.3. Patents / 4.6.4. PhD completed Confidential -­‐ 22 CIRM Activity Report 2016 Eric Kamangu. 9 November 2015. Molecular characterisation of HIV-­‐1 and therapeutic follow-­‐up in patients treated in RDC 4.6.5. Grants and funds PRD ARES 2016 Hayette-­‐Mvumbi. 2016-­‐2021. « Mise en place d’un système de surveillance moléculaire de la résistance de P. falciparum aux antipaludéens par marqueurs moléculaires en RDC. » BIOWIN 2016 Melin P., 2016-­‐2020. “FRISBY -­‐ Fast and Reliable ultra-­‐sensitive identification of Streptococcus B at delivery” FIRS: Krzesinski J-­‐M., Melin P., Jouret F., Descy J 2013-­‐
2015. “Rôle de la flore microbienne intestinale dans le contrôle de la pression artérielle: comparaison du microbiote des sujets normo-­‐ et hyper-­‐tendus”. Continuation en 2016 FIRS: Moutschen M, Melin P., Giot JB, Meex C., Bontems S. 2016-­‐2017. “ Mise au point d’une PCR VZV salivaire pour le diagnostic d’infections herpétiques sans atteintes cutanées, en particulier les atteintes digestives. » pratiques. Le point de vue du microbiologiste, de l’infectiologue et de l’intensiviste. (Invited for oral presentation). MP.Hayette Tuesday’s seminars in infectiology, Liège. MP Hayette, TH
31/5/2016. News from the 26 ECCMID. Paper presented at GLEM, Liège, Belgique. Melin, P., & Meex, C. (2016, June 06). MUTATION en bactériologie ! Acquisition, configuration, implémentation et expérience sur TLA de BD Kiestra. Bruxelles, Belgique: Formations bioMérieux. Melin, P., Descy, J., Meex, C., (Septembre 2016). Les infections de la sphère génitale. Séminaires -­‐ formation. ISP-­‐WIV en collaboration avec l’AFSCA Bruxelles, Belgique -­‐ Melin, P., Sacheli, R. (2016). Vibrio spp chez l’Homme -­‐ Vibrio spp bij de mens. Séminaire du CIP, ULg (28 octobre 2016) Descy Julie, Meex Cécile, Melin Pierrette -­‐ Multi-­‐résistance aux antibiotiques chez les bacilles Gram négatif en 2016: Ampleur du problème, impact clinique et moyens diagnostiques ASM Microbe 2016, June 16-­‐20, 2016, Boston, Massachusetts, USA – P. Melin st 4.6.6. Participations and invitations to congresses, 21 Annual Congress -­‐ Joint Meeting BVIG/SBMI and seminars and research agencies BVIKM/SBIMC (2-­‐3.12.2016), (Belgian society of internal medicine and Belgian society of infectiology and climical th
26 ECCMID Amsterdam 2016. Poster EV0765. Sacheli R.1,2, Utri Tmicrobiology) . Brussel, Belgium. Julie Descy, lecture on 2 , Darfouf R.1,2, Adjetey C. 2,, Hayette M.P. Genotypic invitation : « Infectious disease of the eye: how to characterization of T. mentagrophytes complex strains circulating improve the microbiological diagnosis? ». in Belgium with the Diversilab® system. st
21 Annual Congress -­‐ Joint Meeting BVIG/SBMI and th
26 ECCMID Amsterdam, The Netherlands 2016 – Symposium BVIKM/SBIMC (2-­‐3.12.2016), Belgian society of internal 12.04.2016 – Huynen P. (invited for oral presentation) -­‐ Syphilis medicine and Belgian society of infectiology and climical during pregnancy microbiology) Brussel, Belgium. Huynen P., Libois A. (invited for oral presentation) “How to use serology in th
26 ECCMID Amsterdam 2016 -­‐ Round Table : Sexually Transmitted Infections” GeneXpert GBS (12.04.2016) Invitation to Melin P. as expert and to Meex C., Sacheli, R ESCMID Postgraduate Education Course, Bertinoro, Italy (25-­‐29.09.2016) Huynen P. (invited for oral ISHAM Workshop Dermatophytes, Utrecht, The presentation) – Laboratory diagnosis of syphilis Netherland. Oral communication. Sacheli, R., Adjetey BAHUN, A., Darfouf, R., & Hayette, M.-­‐P. (2016, October Annual DiaSorin Symposium, Brussels (21.04.2016) 29). Application of rep-­‐PCR as molecular typing method Huynen P. (invited for oral presentation) – for dermatophytes. L’automatisation des selles dans un laboratoire de Sérologie Congress of the French Society of medical mycology, Grenoble, 23 March 2016. Poster. Sacheli, R., Utri, T., Séminaire organisé par la Haute Ecole A.Vésale, Liège Abdel-­‐Sadick, H. A., Alfageme Gonzalez, J., Adjetey (15.12.2016) Huynen P. (invited for oral presentation) – Bahun, A., & Hayette, M.-­‐P. Etude de dermatophytes Rôle et place du technologue dans un laboratoire. isolés dans les services de revalidation et physiothérapie d’une structure hospitalière en région Liégeoise GLEM de Rhumatologie, Liège (22.06.2016) Huynen P., (Belgique). Giot J.B. (invited for oral presentation) Borréliose de Lyme : aspects cliniques et prise en charge thérapeutique Pfizer seminar, Temploux, 29 september 2016. Infections fongiques graves: recommandations et situations Confidential -­‐ 23 CIRM Activity Report 2016 Master en Médecine Transfusionnelle, Namur (8.12.2016) Huynen P. -­‐ Virus de l’immunodéficience acquise Mardis midis de l’infectiologie, Liège (19.01.2016) Huynen P., Dumasy A. (invited for oral presentation) – Gestion des épidémies à norovirus Confidential -­‐ 24 CIRM Activity Report 2016 4.7. Clinical Pharmacology laboratory 4.7.1. Main publications Bonnet F, Scheen A. Understanding and overcoming metformin gastrointestinal intolerance. Diabetes Obes Metab. 2016 Dec 17. doi: 10.1111/dom.12854. [Epub ahead of print] Review. PubMed PMID: 27987248. Scheen A J. DPP-­‐4 inhibitor plus SGLT-­‐2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects. Expert Opin Drug Metab Toxicol. 2016 Dec;12(12):1407-­‐
1417. PubMed PMID: 27435042. Scheen AJ. Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-­‐REG OUTCOME. Diabetes Res Clin Pract. 2016 Nov;121:204-­‐214. doi: 10.1016/j.diabres.2016.09.016. Review. PubMed PMID: 27744129. Scheen AJ. SGLT2 Inhibitors: Benefit/Risk Balance. Curr Diab Rep. 2016 Oct;16(10):92. doi: 10.1007/s11892-­‐
016-­‐0789-­‐4. Review. PubMed PMID: 27541294. Scheen AJ. Reappraisal of the diuretic effect of empagliflozin in the EMPA-­‐REG OUTCOME trial: Comparison with classic diuretics. Diabetes Metab. 2016 Sep;42(4):224-­‐33. doi: 10.1016/j.diabet.2016.05.006. Review. PubMed PMID: 27291329. Scheen AJ. Diabetes: Time for reconciliation between cardiologists and diabetologists. Nat Rev Cardiol. 2016 Sep;13(9):509-­‐10. doi: 10.1038/nrcardio.2016.113. PubMed PMID: 27411401. Scheen AJ. Precision medicine: The future in diabetes care? Diabetes Res Clin Pract. 2016 Jul;117:12-­‐21. doi: 10.1016/j.diabres.2016.04.033. Review. PubMed PMID: 27329017. Scheen AJ. Reduction in cardiovascular and all-­‐cause mortality in the EMPA-­‐REG OUTCOME trial: A critical analysis. Diabetes Metab. 2016 Apr;42(2):71-­‐6. doi: 10.1016/j.diabet.2015.12.005. PubMed PMID: 26856453. Scheen AJ. Investigational insulin secretagogues for type 2 diabetes. Expert Opin Investig Drugs. 2016;25(4):405-­‐22. doi: 10.1517/13543784.2016.1152260. Review. PubMed PMID: 26881467. Scheen AJ. Will delayed release metformin provide better management of diabetes type 2? Expert Opin Pharmacother. 2016; 17(5):627-­‐30. doi: 10.1517/14656566.2016.1149166. PubMed PMID: 26830975. Scheen AJ. Dulaglutide (LY-­‐2189265) for the treatment of type 2 diabetes. Expert Rev Clin Pharmacol. 2016;9(3):385-­‐99. doi: 10.1586/17512433.2016.1141046. PubMed PMID: 26761217. 4.7.2. Other publications / 4.7.3. Patents / 4.7.4. PhD completed / 4.7.5. Grants and funds / 4.7.6. Participations and invitations to congresses, seminars and research agencies Scheen A.J. Empa-­‐reg Outcome : le point de vue du diabétologue. Conférence sur invitation présentée au congrès annuel de la Société Francophone du Diabète, Lyon France, Mars 2016. Scheen A.J. Les résultats de réduction de mortalité cardiovasculaire et totale avec l’empagliflozine peuvent-­‐ils s’expliquer par un effet diurétique ? Communication orale présentée au congrès annuel de la Société Francophone du Diabète, Lyon France, Mars 2016. Scheen A.J. Flash-­‐back sur les différentes alertes concernant les antidiabétiques au cours des 10 dernières années. Conférence plénière sur invitation présentée au congrès annuel de la Société Francophone du Diabète, Lyon France, Mars 2016. Scheen A.J. Les nouveaux médicaments antidiabétiques : une approche personnalisée de la prescription. Conférence sur invitation présentée au congrès Innovation & Diabète, Montpellier, France, 3 juin 2016. Scheen A.J. A decade of DPP-­‐4 inhibition : What have we learned ? DPP-­‐4 vs SGLT2 : Which to inhibit ? Invited lecture at the Annual Congress of the European Association for the Confidential -­‐ 25 CIRM Activity Report 2016 Study of Diabetes, Munich, Germany, September 14, 2016. Scheen A.J. Inhiber la DPP-­‐4 ou les SGLT2 : Que choisir chez le patient DT2 ? Conférence sur invitation présentée au Congrès Maghrébin d’Endocrinologie, Tunis, 28 octobre 2016 Scheen A.J. Cibler la voie métabolique du cortisol comme action thérapeutique dans le diabète de type 2. Conférence sur invitation présentée à la Journée Thématique « Diabète et hormones » de la Société Francophone du Diabète, Paris, 9 décembre 2016. Confidential -­‐ 26 CIRM Activity Report 2016 4.8. Hospital and Clinical Pharmacology Unit 4.8.1. Main publications No answer (NA) 4.8.2. Other publications NA 4.8.3. Patents NA 4.8.4. PhD completed NA 4.8.5. Grants and funds NA 4.8.6. Participations and invitations to congresses, seminars and research agencies NA Confidential -­‐ 27 CIRM Activity Report 2016 4.9. Quality assurance Unit 4.9.1. Main events The external recognition obtained by CIRM members evolved during the year 2016. Besides being able to carry out the control of the medicines and the clinical batches by means of physico-­‐
chemical tests (dosages of active ingredients, impurities, ...), the 6 operating entities of Pharmacy Department (LCA, LTP, LAM, LPG, LCP and CAD) as part of CIRM, were certified GMP for endotoxins test and are now able to propose the research of endotoxins in the medicines. These entities also participated to 5 inter-­‐
laboratory testing (PTS) organized by the European Directorate for the Quality of Medicines and HealthCare (EDQM). The following tests were successfully realized: Volumetric Titration, Loss on Drying, Semi-­‐micro determination of Water, Liquid Chromatography-­‐UV and UV-­‐Vis Spectrophotometry. After the GMP-­‐UE label obtained in 2014, the year 2016 was marked by another recognition awarded by WHO (World Health Organization) after a peer review audit based on the existing quality system. Indeed, the Pharmacy Department was prequalified by WHO for the control quality of medicines around the world for United Nations members. At the same time, this label will allow sustaining the quality system environment for training panel to foreigners. In 2016, the CIRM received 16 trainers from Africa and Haiti, in collaboration with the Belgian cooperation Académie de Recherche et de l’Enseignement Supérieur (ARES). Confidential -­‐ 28 CIRM Activity Report 2016 4.10. Pharmaceutical Chemistry laboratory 4.10.1. Main publications Frédérich M, Pirotte B, Fillet M, de Tullio P. Metabolomics as a Challenging Approach for Medicinal Chemistry and Personalized Medicine. J. Med. Chem. (2016), 59:8649-­‐8666. IF: 5.589 Krintel C, Francotte P, Pickering DS, Juknait! L, Pøhlsgaard J, Olsen L, Frydenvang K, Goffin E, Pirotte B, Kastrup JS. Enthalpy-­‐Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2. Biophys. J. (2016), 110:2397-­‐2406. IF : 3.632 Pirotte B, Florence X, Goffin E, Medeiros MB, de Tullio P, Lebrun P. 4-­‐Phenylureido/thioureido-­‐substituted 2,2-­‐
dimethylchroman analogs of cromakalim bearing a bulky 'carbamate' moiety at the 6-­‐position as potent inhibitors of glucose-­‐sensitive insulin secretion. Eur. J. Med. Chem. (2016), 121:338-­‐351. IF : 3.902 Harrouche K, Renard JF, Bouider N, de Tullio P, Goffin E, Lebrun P, Faury G, Pirotte B, Khelili S. Synthesis, characterization and biological evaluation of benzothiazoles and tetrahydrobenzothiazoles bearing urea or thiourea moieties as vasorelaxants and inhibitors of the insulin releasing process. Eur. J. Med. Chem. (2016), 115:352-­‐360. IF : 3.902 Gilissen J, Jouret F, Pirotte B, Hanson J. Insight into SUCNR1 (GPR91) structure and function. Pharmacol. Ther. (2016), 159:56-­‐65. IF : 11.000 Larsen AP, Francotte P, Frydenvang K, Tapken D, Goffin E, Fraikin P, Caignard DH, Lestage P, Danober L, Pirotte B, Kastrup JS. Synthesis and Pharmacology of Mono-­‐, Di-­‐, and Trialkyl-­‐
Substituted 7-­‐Chloro-­‐3,4-­‐dihydro-­‐2H-­‐1,2,4-­‐
benzothiadiazine 1,1-­‐Dioxides Combined with X-­‐ray Structure Analysis to Understand the Unexpected Structure-­‐Activity Relationship at AMPA Receptors. ACS Chem. Neurosci. (2016), 7:378-­‐390. IF : 4.348 Dilly S, Liégeois JF. Structural Insights into 5-­‐HT1A/D4 Selectivity of WAY-­‐
100635 Analogues: Molecular Modeling, Synthesis, and in Vitro Binding. J. Chem. Inf. Model. (2016), 56:1324-­‐1331. IF : 3.657 Hanson J, Chevigné A. GPCRs in immunity: Atypical receptors and novel concepts. Biochem. Pharmacol. (2016), 114:1-­‐2. IF : 5.091 Szpakowska M, Dupuis N, Baragli A, Counson M, Hanson J, Piette J, Chevigné A. Human herpesvirus 8-­‐encoded chemokine vCCL2/vMIP-­‐II is an agonist of the atypical chemokine receptor ACKR3/CXCR7. Biochem. Pharmacol. (2016), 114:14-­‐21. IF : 5.091 Jouret F, Leenders J, Poma L, Defraigne JO, Krzesinski JM, de Tullio P. Nuclear Magnetic Resonance Metabolomic Profiling of Mouse Kidney, Urine and Serum Following Renal Ischemia/Reperfusion Injury. PLoS One (2016), 11:e0163021. IF : 3.057 Blomme A, Costanza B, de Tullio P, Thiry M, Van Simaeys G, Boutry S, Doumont G, Di Valentin E, Hirano T, Yokobori T, Gofflot S, Peulen O, Bellahcène A, Sherer F, Le Goff C, Cavalier E, Mouithys-­‐Mickalad A, Jouret F, Cusumano PG, Lifrange E, Muller RN, Goldman S, Delvenne P, De Pauw E, Nishiyama M, Castronovo V, Turtoi A. Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-­‐negative breast cancer. Oncogene. (2016), in press IF : 7.932 Nokin MJ, Durieux F, Peixoto P, Chiavarina B, Peulen O, Blomme A, Turtoi A, Costanza B, Smargiasso N, Baiwir D, Scheijen JL, Schalkwijk CG, Leenders J, de Tullio P, Bianchi E, Thiry M, Uchida K, Spiegel DA, Cochrane JR, Hutton CA, De Pauw E, Delvenne P, Belpomme D, Castronovo V, Bellahcène A. Methylglyoxal, a glycolysis side-­‐product, induces Hsp90 glycation and YAP-­‐mediated tumor growth and metastasis. Elife. (2016), in press IF : 8.303 4.10.2. Other publications / 4.10.3. Patents / 4.10.4. PhD completed GILISSEN Julie Development of pharmacological tools for the identification of G protein-­‐coupled receptors ligands PhD in Biomedical and Pharmaceutical Sciences (15/03/2016) 4.10.5. Grants and funds Fonds Spéciaux ULg (P. Francotte, co-­‐promoter) (2016-­‐
2017) Développement d’analogues de l’acide ellagique utilisables par voie orale pour le traitement de la malaria Fonds Spéciaux ULg credits sectoriels (P. Francotte, promoter) (2016-­‐2018) Conception et développement de nouveaux antimalariques dérivés de l'acide ellagique actifs par voie orale CDR -­‐ FNRS (P. Francotte, promoter) (2017-­‐2018) Conception des premiers modulateurs allostériques positifs sélectifs des récepteurs au kaïnate Confidential -­‐ 29 CIRM Activity Report 2016 Crédit équipement FNRS (P. de Tullio, B. Pirotte, co-­‐
promoters) (2017-­‐2018) Mise à niveau électronique de la plateforme LC-­‐SPE-­‐
RMN du département de Pharmacie de l’ULg Fonds Spéciaux ULg (P. de Tullio, promoter) (2016-­‐2018) Tests d’efficacité in vivo de nouveaux inhibiteurs la PDH kinase développés contre la néovascularisation choroïdienne induite chez la souris Fonds Feder (P. de Tullio, co-­‐promoter) (2016) développement d’anticorps pour traiter la dégénérescence maculaire liée à l’âge (DMLA) FacMed Research Student (J.F. Liégeois, promotor) (2016-­‐2017) Romain Vitello Synthesis and biological evaluation of crispine E as modulators of SK channels FacMed Research Student (P. de Tullio, promotor) (2016-­‐
2017) Manon Campas FacMed Research Student (P. Francotte, promotor) (2016-­‐2017) Aurore Hans Conception, synthèse et évaluation pharmacologique de dérivés de l’acide caféique potentiellement actifs en tant qu’antimalariques 4.10.6. Participations and invitations to congresses, seminars and research agencies / Confidential -­‐ 30 CIRM Activity Report 2016 4.11. Pharmaceutical Technology and Biopharmacy laboratory 4.11.1. Main publications Thiry J, Krier F, Ratwatte S, Thomassin JM, Jérôme C, Evrard B Hot-­‐Melt Extrusion as a Continuous Manufacturing Process to Form Ternary Cyclodextrin Inclusion Complexes. European Journal of Pharmaceutical Sciences (in press) IF last: 3.35 Thiry J, Lebrun P, Vinassa C, Adam M, Netchacovitch L, Ziemons E, Hubert P., Krier F, Evrard B. Continuous Production of Itraconazole-­‐based Solid Dispersions by Hot Melt Extrusion: Preformulation, Optimization and Design Space Determination. International Journal of Pharmaceutics (in press). IF last: 3.65 Lechanteur A, Furst T, Evrard, B, Delvenne, P., Hubert, P., Piel, G. PEGylation of lipoplexes: The right balance between cytotoxicity and siRNA effectiveness. European Journal of Pharmaceutical Sciences (2016) 93, 493-­‐593. IF last: 3.35 Furst T, Dakwar G, Zagato E, Lechanteur A, Remaut K, Evrard B, Braeckmans K, Piel G. Freeze-­‐dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA. Journal of Controlled Release (2016) Aug 28;236:68-­‐78. IF last: 7.705 Karim R, Palazzo C, Evrard B, Piel, G. Nanocarriers for the treatment of glioblastoma multiforme:Current state-­‐of-­‐the-­‐art. Journal of Controlled Release (2016) 10; 227:23-­‐37. IF last: 7.705 Pestieau A, Krier F, Brouwers A, Streel B, Evrard B. Selection of a discriminant and biorelevant in vitro dissolution test for the development of fenofibrate self-­‐
emulsifying lipid-­‐based formulations. European Journal of Pharmaceutical Sciences (2016) 20; 92:212-­‐9. IF last: 3.35 Thiry J, Broze G, Pestieau A, Tatton A, Baumans F, Damblon C, Krier F, Evrard B. Investigation of a suitable in vitro dissolution test for itraconazole-­‐based solid dispersions. European Journal of Pharmaceutical Sciences (2016) 31; 85:94-­‐105. IF last: 3.35 Furst T, Bettonville V, Farcas E., Frère A., Lechanteur A., Evrard B., Fillet M., Piel G, Servais AC Capillary electrophoresis method to determine siRNA complexation with cationic liposomes. Electrophoresis (2016) 37(20):2685-­‐2691. IF last: 3.028 Netchacovitch L., Thiry J, De Bleye C, Dumont E, Dispas A, Hubert C, Krier F, Sacre PY, Evrard B, Hubert P, Ziemons E. A simple calibration approach based on film-­‐casting for confocal Raman microscopy to support the development of a Hot-­‐Melt Extrusion process. Talanta (2016), 154, 392-­‐399. IF last: 3.545 Frère A, Evrard B, Mottet D, Piel G. Polymeric Nanoparticles as siRNA Drug Delivery System for Cancer Therapy: The Long Road to Therapeutic Efficiency. In A. M., Holban & A., Grumezescu (Eds.), Nanoarchitectonics for Smart Delivery and Drug Targeting (pp. 503-­‐540). Elsevier. 4.11.2. Other publications / 4.11.3. Patents Nuozzi A., Thiry J., Emmerechts C., Beeckman E., Krier F., Evrard B. “Appareillage pour la production en continu de formes orales solides”. BE 100020544, 10 October 2016. 4.11.4. PhD completed THIRY Justine Development of a continuous hot melt extrusion process for manufacturing solid oral dosage forms containing a BCS II drug PhD in Pharmaceutical Sciences (2016) FURST Tania Développement d'un système matriciel permettant la délivrance topique et prolongée de vecteurs d'acides nucléiques pour le traitement des cancers par HPV PhD in Pharmaceutical Sciences (2016) LECHANTEUR Anna Développement et optimisation de nanovecteurs de type lipoplexes pour une application vaginale en vue de traiter des lésions induites par HPV PhD in Pharmaceutical Sciences (2016) FRERE Antoine Développement de vecteurs polymères de type polyplexes à base de nouveaux polymères cationiques biodégradables de type polycarbonates et de siRNA dirigés spécifiquement contre des histones déacétylases PhD in Pharmaceutical Sciences (2016) THORENS Grégory Corrélation des conditions de production et des propriétés physicochimiques de la cellulose microcristalline avec sa fonctionnalité en compression directe PhD in Pharmaceutical Sciences (2016 4.11.5. Grants and funds Confidential -­‐ 31 CIRM Activity Report 2016 GRANTS Prix de l'Académie Royale de Médecine de Belgique, Gilles Dufour Titre du projet: Intérêts des cyclodextrines dans la formulation de préparations galéniques antiasthmatiques Grant Marie-­‐Curie COFUND-­‐Outgoing Fellowships, Anna Lechanteur Titre du projet: New three-­‐dimensional intestinal tissue engineering model as multifunctional platform for drug and nanoparticle absorption studies AAPS Oral Absorption Focus Group Graduate Student Poster Award, Justine Thiry Titre du poster: « Original study of the bioavailability Enhancement of Itraconazole-­‐based Solid Dispersions Produced by Hot Melt Extrusion in the Framework of the Three Rs rule » Travelship from the « Ancients Chimistes de l’Université de Liège », Justine Thiry Oral communication: « Hot Melt Extrusion as a New Method to Form Inclusion Complexes with Cyclodextrins» (PBP Glasgow) Fond Léon Fredericq, Promotion des Jeunes Talents le 18 novembre 2016, Reatul Karim FUNDS RW, Beware N°1510632 (2016-­‐2018) Titre du projet : Administration pulmonaire de liposomes encapsulant une molécule d’origine naturelle de type flavonoïde pour le traitement du cancer du poumon Credit Classique, ULg (2016-­‐2017) Titre du projet : Administration pulmonaire de liposomes encapsulant une molécule d’origine naturelle de type flavonoïde pour le traitement du cancer du poumon RW/FEDER SKINANO convention en cours (2016-­‐2020) Titre du projet : Nouvelle thérapie génique à base de lipoplexes administrés par voie topique pour prévenir la cancérisation d'un champ subclinique associé à une kératose actinique et/ou à un cancer de la peau non-­‐
mélanome FEDER PHARE, convention en cours, (2017-­‐2021) 4th Congress on Innovation in Drug Delivery, Antibes-­‐
Juan-­‐Les-­‐Pins, France 26-­‐28 September 2016 19th Forum of Pharmaceutical Sciences, Bruxelles, Belgique, October 2016. AAPS Annual Meeting and Exposition Denver, USA, November 2016 SF Nano Annual Meeting, Paris, France, 12-­‐14 December 2016 4.11.6. Participations and invitations to congresses, seminars and research agencies 10th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, Glasgow, April 2016 Confidential -­‐ 32 CIRM Activity Report 2016 4.12. Pharmacognosy laboratory 4.12.1. Main publications Tshisekedi Tshibangu, P., Mutwale Kapepula, P., Kabongo Kapinga, M. J., Kabika Lupona, H., Kabamba Ngombe, N., Dibungi T. Kalenda, P., Jansen, O., Wauters, J.-­‐N., Tits, M., Angenot, L., Rozet, E., Hubert, P., Marini Djang’Eing’A, R., & Frederich M. Fingerprinting and validation of a LC-­‐DAD method for the analysis of biflavanones in Garcinia kola-­‐based antimalarial improved traditional medicines. J. Pharm. Biomed. Anal. (2016), 128(2016), 382-­‐390. I.F. 2.979. P. Tshisekedi Tshibangu, P. Mutwale Kapepula, M.J. Kabongo Kapinga, A. Tujibikila Mukuta, Dibungi T. Kalenda, Alembert T. Tchinda, Ange A. Mouithys-­‐
Mickalad, O. Jansen, E. Cieckiewicz, M. Tits, L. Angenot, and M. Frédérich. Antiplasmodial activity of Heinsia crinita (Rubiaceae) and identification of new iridoids. J. Ethnopharmacol. (2016), in press. I.F. 2.998. Paulin Mutwale Kapepula, Patricia Mbombo Mungitshi, Thierry Franck, Ange Mouithys-­‐Mickalad, Dieudonné Mumba Ngoyi, Pascal Dibungi T. Kalenda, Nadege Kabamba Ngombe, Didier Serteyn, Monique Tits, Michel Frédérich and Jean-­‐Jacques Tamfum Muyembe. Antioxidant potentiality of three herbal teas consumed in Bandundu rural areas of Congo. (2016) in press. I.F. 0.919. Frederich, M., Pirotte, B., Fillet, M., & De Tullio, P. Metabolomics as a Challenging Approach for Medicinal Chemistry and Personalized Medicine. Journal of Medicinal Chemistry. (2016), 59, 8649−8666 I.F. 5.447. Mskhiladze, L., Chincharadze, D., St-­‐Gelais, A., Mshvildadze, V., Pichette, A., Ledoux, A., Tits, M., & Frederich, M. Isolation and Identification of Steroid and Flavonoid Glycosides from the Flowers of Allium gramineum. International Journal of Pharmaceutical Sciences and Drug Research (2016), 8(4), 240-­‐243. Paltinean, R., Toiu, A., Wauters, J.-­‐N., Frederich, M., Tits, M., Angenot, L., Tamas, M., & Crisan, G. Phytochemical analysis of Fumaria officinalis. Farmacia (2016), 64(3), 409-­‐413. I.F. 1.005. J. Govinden-­‐Soulange, D. Lobine, M. Frederich, H. Kodja, M.P.A. Coetzee, V.M. Ranghoo-­‐Sanmukhiya. Metabolomic and molecular signatures of Mascarene Aloes using a multidisciplinary approach. South African Journal of Botany (2017), 108, 137-­‐143. 4.12.2. Other publications Marquise, N., Chevallier, F., Nassar, E., Frederich, M., Ledoux, A., Halauko, Y. S., Ivashkevich, O. A., Matulis, V. E., Roisnel, T., Dorcet, V., & Mongin, F. Substituted azafluorenones: access from dihalogeno diaryl ketones by palladium-­‐catalyzed auto-­‐tandem processes and evaluation of their antibacterial, antifungal, antimalarial and antiproliferative activities. Tetrahedron (2016), 72(6), 825-­‐836. I.F. 2.641. Kengne, A. B. O., Tene, M., Tchinda Tiabou, A., Tane, P., & Frederich, M. Terpenoids from Phaulopsis imbricata (Acanthaceae). Journal of Medicinal Plants Research (2016) Hamaïdia, M., Barez, P.-­‐Y., Carpentier, A., Lebecque, S., Miazek, K., Paul, A., Neelature Sriramareddy, S., Staumont, B., Danthine, S., Deleu, M., Frederich, M., De Pauw, E., Delaplace, P., Delvigne, F., Goffin, D., Ongena, M., DUYSINX, B., LOUIS, R., cosse, J.-­‐P., & Willems, L. From Valeriana officinalis to cancer therapy: the success of a bio-­‐sourced compound. BASE (2016), 20. I.F. 0.457 Miazek, K., Lebecque, S., Hamaïdia, M., Paul, A., Danthine, S., Willems, L., Frederich, M., De Pauw, E., Deleu, M., Richel, A., & Goffin, D. Sphingolipids: promising lipid-­‐class molecules with potential applications for industry. BASE (2016), 20(S1)), 321-­‐336. I.F. 0.457. Paul, A., Frederich, M., Uyttenbroeck, R., Hatt, S., Malik, P., Lebecque, S., Hamaïdia, M., Miazek, K., Goffin, D., Willems, L., Deleu, M., Fauconnier, M.-­‐L., Richel, A., De Pauw, E., Blecker, C., Monty, A., Francis, F., Haubruge, E., & Danthine, S. Grasshoppers as a food source? A review. BASE (2016). 20(AgricultureIsLife), 337-­‐352. I.F. 0.457. Talla, E., Yaya Gbaweng, J., Mokale, L., Abdou, J.-­‐P., Tchinda Tiabou, A., Frederich, M., & Mbafor, J. Chemical constituents from Erythrina droogmansiana (Fabaceae), radical scavenging and antibacterial potential of some extracts and compounds. Natural Products : An Indian Journal, 12(1), 12-­‐20. Uyttenbroeck, R., Hatt, S., Paul, A., Boeraeve, F., Piqueray, J., Francis, F., Danthine, S., Frederich, M., Dufrêne, M., Bodson, B., & Monty, A. Pros and cons of flowers strips for farmers. A review. BASE (2016), 20(s1), 225-­‐235. I.F. 0.457. Angélique Nicolas Messi, Joséphine Ngo Mbinga,, Joseph Thierry Ndongo, Maximilienne Ascension Nyegue, Alembert Tiabou Tchinda, Flora Ladoh Yemeda, Michel Frédérich, Dieudonné Emmanuel Pegnyemba. Phenolic compounds from the roots of Ochna schweinfurthiana and their antioxidant and antiplasmodial activities. Phytochemistry Lett. (2016), 17, 119-­‐125. 4.12.3. Patents / 4.12.4. PhD completed Confidential -­‐ 33 CIRM Activity Report 2016 ESTERS Virginie Contribution à l’étude d’Umutambasha, plante toxique du Rwanda PhD in Pharmaceutical Sciences (2016) 4.12.5. Grants and funds Fonds spéciaux FM: MALAGIC (2016-­‐2017) Development of analogs of ellagic acid for oral use in the treatment of malaria Compléments FEDER : METABO (2016-­‐2021) Tropical Plant Factory – Projet G – Pharmacopée et identification de métabolites secondaires de haute valeur ajoutée. RW-­‐DG06: Pulmolip (2016-­‐2018) (co-­‐promotor) Administration pulmonaire de liposomes encapsulant une molécule d’origine naturelle pour la prévention et/ou le traitement du cancer du poumon. FEDER -­‐ Réunion : PHAR (2017-­‐2019) Valorisation pharmacologique de la biomasse terrestre et marine de la zone sud-­‐ouest de l’Océan Indien par voies chimique et biotechnologique. – PHAR FEDER -­‐ RW : ECOSOL (2017-­‐2021) Projet ECOSOL du portefeuille de la ville de Sambreville ARES : PRD (2015-­‐2019) Optimalisation de la pharmacopée traditionnelle rwandaise. ARES : PII (2015-­‐2016) Mise en place d’un herbier national des plantes médicinales et d’une chimiothèque au Burkina Faso. RW-­‐DG06 : PPP 1318232 (2015-­‐2016) COLEXTRACT FRS-­‐FNRS : FRSM N° T.0190.13 (2013-­‐2017) PDR: Identification de substances naturelles antiparasitaires. 4.12.6. Participations and invitations to congresses, seminars and research agencies 9th Joint Natural Products Conference. Copenhagen, Denmark, July 24-­‐28, 2016. Confidential -­‐ 34 CIRM Activity Report 2016 4.13. Tumors and Development Biology laboratory 4.13.1. Main publications Blacher S, Gérard C, Gallez A, Foidart JM, Noël A, Péqueux C. Quantitative assessment of mouse mammary gland morphology using automated digital image processing and TEB detection. Endocrinology. 2016 Apr;157(4):1709-­‐16. IF=4,503 García-­‐Caballero M, Blacher S, Paupert J, Quesada AR, Medina MA, Noël A. Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-­‐C/VEGFR-­‐3 signaling pathway. Br J Pharmacol. 2016 Jun;173(12):1966-­‐87. IF=4,842 Gérard C, Gallez A, Dubois C, Drion P, Delahaut P, Quertemont E, Noël A, Pequeux C. Accurate Control of 17β-­‐Estradiol Long-­‐Term Release Increases Reliability and Reproducibility of Preclinical Animal Studies. J Mammary Gland Biol Neoplasia. 2016 Nov 26. IF=4,526 Leroi N, Lallemand F, Coucke P, Noel A, Martinive P. Impacts of Ionizing Radiation on the Different Compartments of the Tumor Microenvironment. Front Pharmacol. 2016 Mar 30;7:78. doi: 10.3389/fphar.2016.00078. eCollection 2016. IF=3,802 Truong A, Yip C, Paye A, Blacher S, Munaut C, Deroanne C, Noel A, Sounni NE. Dynamics of internalization and recycling of the prometastatic membrane type 4 matrix metalloproteinase (MT4-­‐MMP) in breast cancer cells. FEBS J. 2016 Feb;283(4):704-­‐22. IF=4,001 Withofs N, Martinive P, Vanderick J, Bletard N, Scagnol I, Mievis F, Giacomelli F, Coucke P, Delvenne P, Cataldo D, Gambhir SS, Hustinx R. [(18)F]FPRGD2 PET/CT imaging of integrin αvβ3 levels in patients with locally advanced rectal carcinoma. Eur J Nucl Med Mol Imaging. 2016 Apr;43(4):654-­‐62. IF=5,383 4.13.2. Other publications Amand M, Erpicum C, Gilles C, Noël A, Rahmouni S. Functional Analysis of Dual-­‐Specificity Protein Phosphatases in Angiogenesis. Methods Mol Biol. 2016;1447:331-­‐49. Bastos DC, Paupert J, Maillard C, Seguin F, Carvalho MA, Agostini M, Coletta RD, Noël A, Graner E. Effects of fatty acid synthase inhibitors on lymphatic vessels: an in vitro and in vivo study in a melanoma model. Lab Invest. 2016 Dec 5. Bourcy M, Suarez-­‐Carmona M, Lambert J, Francart ME, Schroeder H, Delierneux C, Skrypek N, Thompson EW, Jerusalem G, Berx G, Thiry M, Blacher S, Hollier BG, Noel A, Oury C, Polette M, Gilles C. Tissue factor induced by epithelial-­‐mesenchymal transition triggers a pro-­‐coagulant state that drives metastasis of circulating tumor cells. Cancer Res. 2016 May 24. pii: canres.2263.2015. IF=9,329 Butler GS, Connor AR, Sounni NE, Eckhard U, Morrison CJ, Noël A, Overall CM. Degradomic and yeast 2-­‐hybrid inactive catalytic domain substrate trapping identifies new membrane-­‐type 1 matrix metalloproteinase (MMP14) substrates: CCN3 (Nov) and CCN5 (WISP2). Matrix Biol. 2016 Jul 26. pii: S0945-­‐053X(16)30165-­‐2. de Landsheere L, Brieu M, Blacher S, Munaut C, Nusgens B, Rubod C, Noel A, Foidart JM, Nisolle M, Cosson M. Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse? Int Urogynecol J. 2016 Apr;27(4):629-­‐35. IF=1,961 Tskitishvili E, Pequeux C, Munaut C, Viellevoye R, Nisolle M, Noël A, Foidart JM. Use of Estetrol with other Steroids for Attenuation of Neonatal Hypoxic-­‐Ischemic brain injury: to combine or not to combine? Oncotarget. 2016 May 25. IF=6,359 Tskitishvili E, Viellevoye R, Gérard C, Pequeux C, Munaut C, Nisolle M, Noël A, Foidart J-­‐M (2016). Neonatal Hypoxic-­‐Ischemic Encephalopathy: a new view of an old problem. Références en Gynécologie Obstétrique, 17(1-­‐1). 4.13.3. Patents / 4.13.4. PhD completed Alice TRUONG: «La métalloprotéinase membranaire de type-­‐4 (MT4-­‐MMP) : étude de la régulation et des fonctions de la protéine dans des cellules tumorales” Laurie HENRY: «Restauration de la fertilité des patientes cancéreuses par cryopréservation de tissu ovarien» Morgane BOURCY, : «Activation de la coagulation par la transition épithélio-­‐mésenchymateuse : impact sur la colonisation métastatique» Natacha LEROI: «Impact de la radiothérapie néoadjuvante et du délai entre la radiothérapie et la chirurgie sur le microenvironnement tumoral et la dissémination métastatique» Maïté FRANSOLET : «Contribution à l’étude de la restauration de la fertilité féminine au moyen d’un modèle de xénogreffe de tissue ovarien cryopréservé». 4.13.5. Grants and funds Confidential -­‐ 35 CIRM Activity Report 2016 Télévie N° 7.4545.16 (2016-­‐2018) « Etude des mécanismes moléculaires impliqués dans la guidance des cellules endothéliales au cours de la lymphangiogenèse tumorale » Télévie N° 7.4589.16 (2016-­‐2018) « Nouvelles méthodes d’analyse d’images pour l’étude de la migration cellulaire associée à la progression cancéreuse » Télévie N° 7.4571.16 (2016-­‐2018) Rôle des ADAM dans le mésothéliome » Télévie N° 7.4597.16 (2016-­‐2018) « Etude des mécanismes d’activation des récepteurs aux oestrogèens par l’estetrol et/ou la progestérone dans le sein normal et tumoral » Télévie N°7.4617.16 (2016-­‐2018) « Cibler un axe Transition-­‐Epithélio-­‐
Mésenchymateuse/coagulation dans les Cellules Tumorales Circulantes (CTCs) pour interférer avec la colonisation métastatique » PDR T.0059.15 (2015-­‐2019) « Exploration of EGFR/MT4-­‐MMP axis for improving anti-­‐
EGFR targeted therapy » CDR J.0161.16 (2016-­‐2017) VEGFR-­‐3 trafficking and signaling regulating VEGF-­‐C-­‐
mediated guidance of lymphatic endothelial cells during lymphangiogenesis 4.13.6. Participations and invitations to congresses, seminars and research agencies Oulu (Finlande) : February 22, 2016 Faculty of Biochemistry and Molecular Medicine University of Oulu, Invited Speaker Seminar presentation « The Tumor host-­‐interface in tumor adaptation to treatment » -­‐Montpellier (France): May 20, 2016 4th SIRIC Montpellier Cancer Annual Meeting, Invited Speaker “The Tumor-­‐host interface in tumor progression and adaptation to treatment” Rennes (France): December 1, 2016 5th day of the Young Researchers of IRSET “How can we overcome tumor adaptation to anti-­‐
angiogenic treatment” Invited Speaker Confidential -­‐ 36 CIRM Activity Report 2016 4.14. Biological and Industrial Chemistry laboratory 4.14.1. Main publications Paul, A., Frederich, M., Uyttenbroeck, R., Malik, P., Filocco, S., Richel, A., Heuskin, S., Alabi, T., Megido, R.C., Franck, T., Bindelle, J., Maesen, P., Francis, F., Lognay, G., Blecker, C., Haubruge, E., Danthine, S. Nutritional composition and rearing potential of the meadow grasshopper (Chorthippus parallelus Zetterstedt) (2016) Journal of Asia-­‐Pacific Entomology, 19 (4), pp. 1111-­‐1116. Istasse, T., Jacquet, N., Berchem, T., Haubruge, E., Nguyen, B.K., Richel, A. Extraction of honey polyphenols: Method development and evidence of cis isomerization (2016) Analytical Chemistry Insights, 2016 (11), pp. 49-­‐
57. Miazek, K., Lebecque, S., Hamaidia, M., Paul, A., Danthine, S., Willems, L., Frederich, M., De Pauw, E., Deleu, M., Richel, A., Goffin, D. Sphingolipids: Promising lipid-­‐class molecules with potential applications for industry. A review [Sphingolipides: Des molécules lipidiques à haut potentiel de valorisation présentant de nombreuses applications industrielles (synthèse bibliographique)] (2016) Biotechnology, Agronomy and Society and Environment, 20 (S1), pp. 321-­‐336. Paul, A., Frederich, M., Uyttenbroeck, R., Hatt, S., Malik, P., Lebecque, S., Hamaidia, M., Miazek, K., Goffin, D., Willems, L., Deleu, M., Fauconnier, M.-­‐L., Richel, A., De Pauw, E., Blecker, C., Monty, A., Francis, F., Haubruge, E., Danthine, S. Grasshoppers as a food source? A review [Les criquets: Une nouvelle source d’aliments ? (synthèse bibliographique)] (2016) Biotechnology, Agronomy and Society and Environment, 20 (S1), pp. 337-­‐352. 4.14.2. Other publications Schmetz, Q., Maniet, G., Jacquet, N., Teramura, H., Ogino, C., Kondo, A., Richel, A. Comprehension of an organosolv process for lignin extraction on Festuca arundinacea and monitoring of the cellulose degradation (2016) Industrial Crops and Products, 94, pp. 308-­‐317. Costes, L., Laoutid, F., Aguedo, M., Richel, A., Brohez, S., Delvosalle, C., Dubois, P. Phosphorus and nitrogen derivatization as efficient route for improvement of lignin flame retardant action in PLA (2016) European Polymer Journal, 84, pp. 652-­‐667. Sallem-­‐Idrissi, N., Vanderghem, C., Pacary, T., Richel, A., Debecker, D.P., Devaux, J., Sclavons, M. Lignin degradation and stability: Volatile Organic Compounds (VOCs) analysis throughout processing (2016) Polymer Degradation and Stability, 130, pp. 30-­‐
37. Odjo, S., Béra, F., Jacquet, N., Richel, A., Malumba, P. Characterization of saccharides released during an in vitro pepsin-­‐pancreatin digestion of corn flour using HPAEC-­‐PAD (2016) Starch/Staerke, 68 (7-­‐8), pp. 691-­‐699. Sóti, V., Jacquet, N., Apers, S., Richel, A., Lenaerts, S., Cornet, I. Monitoring the laccase reaction of vanillin and poplar hydrolysate (2016) Journal of Chemical Technology and Biotechnology, 91 (6), pp. 1914-­‐1922. Tahiri, A., Richel, A., Destain, J., Druart, P., Thonart, P., Ongena, M. Comprehensive comparison of the chemical and structural characterization of landfill leachate and leonardite humic fractions (2016) Analytical and Bioanalytical Chemistry, 408 (7), pp. 1917-­‐1928. Perimenis, A., van Aarle, I.M., Nicolay, T., Jacquet, N., Meyer, L., Richel, A., Gerin, P.A. Metabolic profile of mixed culture acidogenic fermentation of lignocellulosic residues and the effect of upstream substrate fractionation by steam explosion (2016) Biomass Conversion and Biorefinery, 6 (1), pp. 25-­‐
37. Bombeck, P.-­‐L., Hébert, J., Richel, A. Enzymatic hydrolysis to produce nanocellulose in an integrated forest biorefinery strategy. A review [L’utilisation de l’hydrolyse enzymatique pour la production de nanocellulose dans une stratégie de bioraffinage forestier intégré (Synthèse Bibliographique)] (2016) Biotechnology, Agronomy and Society and Environment, 20 (1), pp. 94-­‐103. Roger, N., Moerman, R., Carvalheiro, L.G., Aguirre-­‐
Guitiérrez, J., Jacquemart, A.-­‐L., Kleijn, D., Lognay, G., Moquet, L., Quinet, M., Rasmont, P., Richel, A., Vanderplanck, M., Michez, D. Impact of pollen resources drift on common bumblebees in NW Europe (2016) Global Change Biology. Article in Press. Wobiwo, F. A., Emaga, T., Fokou, E., Boda, M., Gillet, S., Deleu, M., Richel, A., Gerin, P. Comparative biochemical methane potential of some varieties of residual banana biomass and renewable energy potential (2016) Biomass Conversion and Biorefinery. Article in Press Arshadi, Mehrdad; Attard, Thomas M.; Lukasik, Rafal M.; Brncic, Mladen; da Costa Lopes, Andre M.; Finell, Michael; Geladi, Paul; Gerschenson, Lia Noemi; Gogus, Fahrettin; Herrero, Miguel; Hunt, Andrew J.; Ibanez, Elena; Kamm, Birgit; Mateos-­‐Aparicio, Inmaculada; Matias, Ana; Mavroudis, Nikolaos E.; Montoneri, Enzo; Confidential -­‐ 37 CIRM Activity Report 2016 Morais, Ana Rita C.; Nilsson, Calle; Papaioannou, Emmanouil H.; Richel, Aurore; Ruperez, Pilar; Skrbic, Biljana; Bodroza Solarov, Marija; Svarc-­‐Gajic, Jaroslava; Waldron, Keith W.; Yuste-­‐Cordoba, F. J. Pre-­‐treatment and extraction techniques for recovery of added value compounds from wastes throughout the agri-­‐food chain (2016) Green Chemistry, Article in Press Vanderplanck Maryse; Decleves Sylvain; Roger Nathalie; Michez Denis; Decroo Corentin; Gerbaux Pascal; Caulier Guillaume; Glauser Gaetan; Lognay Georges; Richel Aurore, Escaravage Nathalie Is non-­‐host pollen suitable for generalist bumblebees? (2016) Insect Science, Article in Press. 4.14.3. Patents / 4.14.4. PhD completed / 4.14.5. Grants and funds RW FIRST SPIN OFF Exercice 2016 CELLOBIO (2016-­‐2018) Développement d’une activité économique centrée sur les dérivés de la cellulose, plus particulièrement le cellobiose au départ de matières premières végétales renouvelables RW Partenariat Privé Public (Mithra) COLEXTRACT (2014-­‐
2016) Extraction de molécules valorisables à partir du colza RW Programme d’Excellence FOOD4GUT (2014-­‐2016) Approche nutritionelle novatrice de l’obésite basée sur l’apport en nutriments colliques : aspects biologiques, comportementaux et sociétaux ème
RW Projet Plan Marshall 2.Vert, GreenWin 9 appel à projet, VALICELL (2014-­‐2017) Valorisation des lignines et de la cellulose issues des effluents des industries papetières INTERREG V FWV COMPOSENS (2016-­‐2020) Développement transfrontalier de matériaux composites polymères – fibres naturelles. Prise en compte des aspects émissifs et sensoriels FEDER (2014-­‐2020) Portefeuille LCFM (Low Carbon Footprints Materials) Projet BIOMAT_3 Molécules biosourcées pour la production de nouveaux matériaux FEDER (2014-­‐2020) Portefeuille VERDIR Projet BioResidus Valorisation des résidus de plantes pharmaceutiques après extraction des composés d’intérêt (métabolites secondaires) RW Avance Recupérable Recherche Industrielle TECHNOSPONGE (2015-­‐2017) Production d’une nouvelle gamme de cellulose pour des applications dans la conception d’éponges naturelles Fonds Spéciaux-­‐ARC-­‐FSR (2015-­‐2019) ROOTSTOCK Analysis of PEBP-­‐genes functions in the induction of storage roots 4.14.6. Participations and invitations to congresses, seminars and research agencies nd
2 Integrated Plant and Algal Phenomics Meeting (IPAP), Prague, Czech Republic, September 2016 th
6 6th International Conference on Engineering for Waste and Biomass Valorisation, Albi, France, May 2016 FP1306 COST Action -­‐ Second Workshop & Third MC Meeting, Dubrovnik, Croatie, April 5, 2016 Journées Jeunes Chercheurs Condorcet 2016 (Université de Reims), Reims, France, January 20, 2016. 1st International Conference on Bioresource Technology (BIORESTEC), Sitges, Espagne, October 2016 Chaire universitaire qualité -­‐ 22ème édition "La Qualité: un plus pour l"économie circulaire ?", Gembloux, Belgique, October 2016 Symposium « Exploring lignocellulosic Biomass », Reims, France, June 23, 2016-­‐11-­‐18 10th symposium gut microbiology 20 years and counting, Clermont Ferrand, France, June 20, 2016 2d édition -­‐ Conférences internationales: Chimie verte et Biotechnologie blanche, deux industries d'avenir pour la Wallonie!, Gembloux, Belgique, June 12-­‐13, 2016 Quatrièmes Journées Scientifiques de l'Agro-­‐Alimentaire, Sousse, Tunisie, March 21, 2016 Confidential -­‐ 38 CIRM Activity Report 2016 4.15. Oxygen Biochemistry Group 4.15.1. Main publications 1: Mendoza L, Lejeune JP, Caudron I, Detilleux J, Sandersen C, Deliège B, Serteyn D. Impact of feeding and housing on the development of osteochondrosis in foals-­‐A longitudinal study. Prev Vet Med. 2016 May 1;127:10-­‐4. IF: 2.182 2: Zholobenko A, Mouithys-­‐Mickalad A, Modriansky M, Serteyn D, Franck T. Polyphenols from Silybum marianum inhibit in vitro the oxidant response of equine neutrophils and myeloperoxidase activity. J Vet Pharmacol Ther. 2016 Dec; 39 (6):592-­‐601. IF: 1.279 4.15.2. Other publications Salciccia A, Grulke S, de la Rebière de Pouyade G, Franck T, Detilleux J, Serteyn D, Sandersen C. Assessment of systemic inflammation by time-­‐trends of blood granulocyte count and plasma myeloperoxidase and elastase concentrations following colic surgery in horses. J Vet Emerg Crit Care (San Antonio). 2016 Jul;26(4):541-­‐8. doi: 10.1111/vec.12481. IF: 1.122 Blommaert D, Franck T, Donnay I, Lejeune JP, Detilleux J, Serteyn D. Substitution of egg yolk by a cyclodextrin-­‐cholesterol complex allows a reduction of the glycerol concentration into the freezing medium of equine sperm. Cryobiology. 2016 Feb; 72(1):27-­‐32. IF: 1.920 Peugnet P, Robles M, Mendoza L, Wimel L, Dubois C, Dahirel M, Guillaume D, Camous S, Berthelot V, Toquet MP, Richard E, Sandersen C, Chaffaux S, Lejeune JP, Tarrade A, Serteyn D, Chavatte-­‐Palmer P. Correction: Effects of Moderate Amounts of Barley in Late Pregnancy on Growth, Glucose Metabolism and Osteoarticular Status of Pre-­‐Weaning Horses. PLoS One. 2016 Dec 2;11(12):e0167604. IF: 3.54 Kapepula PM, Mbombo Mungitshi P, Franck T, Mouithys-­‐Mickalad A, Mumba Ngoyi D, Kalenda PD, Kabamba Ngombe N, Serteyn D, Tits M, Frédérich M, Tamfum Muyembe JJ. Antioxidant potentiality of three herbal teas consumed in Bandundu rural areas of Congo. Nat Prod Res. 2016 Dec 1:1-­‐4. IF: 1.057 4.15.3. Patents / 4.15.4. PhD completed / 4.15.5. Grants and funds / CORD works in subcontracting (R&D) in the project granted by Walloon Region (70%) and RevaTis (30) on the characterization of the mitochondrial function of muscle-­‐derived stem cells; Indice qualification Regional and Federal Funds: WaLinnov Project (2016): CURSTEM (as Promotor of the project) on the muscle-­‐
derived stem cells doped by a water soluble curcumin-­‐
betacyclodextrine complex (NDS27). 4.15.6. Participations and invitations to congresses, seminars and research agencies th
7 World Congress on Targeting Mitochondria (Oct. 24-­‐
26, 2016). Berlin, Germany th
Organization of Congress: 24 Benelux EPR Society Meeting (Mai 2016) in Liège, Belgium Confidential -­‐ 39 CIRM Activity Report 2016 5. COMMUNICATION WITHIN THE CIRM
During the year 2016, CIRM organized 10 seminars for students and researchers of the center. Seminars are organized once a month on lunchtime. The first seminar of the year, on 29 January 2016, informed the CIRM members of the new structure set up in the center. Then, during the year, we had the pleasure of hearing various researchers from the center came to present their research themes. In general, the seminars first welcome a senior researcher who presents a thematic, a method, a problem in a general way. This general presentation is then followed by the presentation of a young researcher, usually a PhD student who presents his research topic related to the topic introduced by the senior researcher. In 2016, we had the pleasure of listening: • On February 18: Pascal de Tullio and then Justine Leenders of the Medicinal chemistry group who talked about "Metabolomics and personalized medicine" and then "Study of ischemia-­‐
reperfusion injury by metabolomics" • On March 24: Roland Marini and Pierre Yves Sacré from Analytical chemistry group who addressed the theme: "Falsified medicines: From myth to reality; From reality to detection " • On April 21: Marie-­‐Louise Scippo and Coraline Simon of the Laboratory of Analysis of food "Steroid like activity of migration compounds from non-­‐polycarbonate plastic baby bootles" and "Endocrine active compounds in food contact materials" • On May 19: Marianne Fillet and Aurore Napp of the Analytical pharmaceutical chemistry group: "Discovery and quantification of new biomarkers for preventive and predictive medicine" and "Analytical challenges for the determination of alpha-­‐synuclein and its oligomeric forms in the context of Parkinson disease" • On June 16: Brigitte Evrard and Aude Pestieau of the Pharmaceutical technology group: "Pharmaceutical applications of supercritical fluids" and "Increase of bioavailability of BCSII active molecules formulated with the help of CO2 supercritical technology" • The first seminar of the academic year 2016-­‐17, in October, has traditionally welcomed new researchers from the center. This year we welcome 4 new PhD students and 2 post-­‐doc researchers back to CIRM after a post-­‐doc position abroad. • On November 16: Michel Frédérich and Alison Ledoux of the laboratory of Pharmacognosy "Potential antimalarials from tropical plants and natural products" • On December 14: Véronique Delcenserie and Sandrine Dufourny, Farah, Veterinary Public Health: "A dynamic digestive model: from the human (SHIME) to the porcine model (Piglet SPIME)". During this year we also had the opportunity to host professors from abroad who gave us the pleasure to give lectures for researchers of the center. We welcomed: • Professor Graeme Milligan of the University of Glasgow, who gave a lecture on Tuesday, March 15, entitled "Long Chain Fatty Acid Receptors and their potential therapeutic roles"; • Professor Gaia Colombo, Professor of Pharmaceutical Technology at the University of Ferrara in Italy, who gave a lecture entitled "Innovation in pharmaceuticals to personalized medicines" • Professor Karine Andrieux of the University of Paris Descartes who gave a lecture on 7/07 on "Anti-­‐Abeta antibody decorated nanoparticles correct memory defect in Alzheimer's disease animal model." Finally, it should be noted that on November 29, 2016, the first edition of the "CIRM Newsletter" was published. This Newsletter is intended to diffuse important informations within CIRM. Quarterly diffusion is planned Confidential -­‐ 40 CIRM Activity Report 2016 6. CIRM TECHNOLOGICAL PLATFORMS TO SUPPORT RESEARCH
The CIRM expertise and services are organized around three following platforms: -­‐ Drug discovery platform -­‐ Drug development and analytical platform -­‐ Clinical platform These platforms are described on the website and accessible through an online request form (http://www.cirm-­‐ulg.be/documents/Request_form_CIRM_platform.pdf). Four technological hubs are supporting these platforms: -­‐ MaS-­‐Santé Hub -­‐ NMR-­‐Santé Hub -­‐ Vibra-­‐santé Hub -­‐ SCF-­‐santé Hub In November 2016, the NMR-­‐santé Hub has been implemented with a new High field NMR system. Indeed, a Bruker Avance HD 700 MHz equipped with a samplejet and a TCI cryoprobe has been installed in the B6C building. This system, which is fully accessible for the CIRM members, completes the existing Bruker Avance 500 MHz installed in the B36 buiding. Confidential -­‐ 41