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1. Shaping the Future of Research: A perspective from early career researchers in Vancouver, Canada [version 1; referees: 1 approved with reservations, 1 not approved]

Author

Peter G.K. Clark, James M. McCoy, Jenny H.L. Chik, Azadeh HajiHosseini, Manuel Lasalle, Brianne A. Kent, and Stefanie L. Vogt

Subjects
Opinion Article, Articles, training, funding, mentoring, junior scientists, career development, science policy, research enterprise
Abstract

Future of Research is an organization dedicated to championing, engaging, and empowering early career researchers (ECRs). The organization was founded in 2014 and has since inspired other groups to advocate for a more equitable and sustainable research enterprise. Here we report the findings of the Future of Research Vancouver Symposium. The goals of the Vancouver symposium were to ascertain the perspective of ECRs in Canada and to outline pathways to a sustainable future for Canadian research. The symposium had two sessions. The first session was a series of talks that were intended to prepare attendees with an informed understanding of several perspectives in the science enterprise, with a particular focus on the Canadian system. The second session was a series of interactive workshops to identify the greatest challenges facing ECRs in Canada and to propose solutions. The results of the workshops illuminated three main themes for the challenges facing Canadian ECRs: funding, mentorship, and the divide between academia and other sectors. These themes are similar to those discussed at the Future of Research symposiums in the United States, emphasizing that these issues are not isolated to Canada; however, Canadian policies are trailing behind the progress being made in other countries.

Published
2018
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3. Generation and structure-activity relationships of novel imidazo-thienopyridine based TLR7 agonists: application as payloads for immunostimulatory antibody drug-conjugates

Author

Michael G. Brant, Graham A.E. Garnett, Joy Guedia, Manuel Lasalle, Samuel Lawn, Mark E. Petersen, Renee Duan, Jose Mendez-Campos, Truman Hirkala-Schaefer, Geoffrey C. Winters, and Stuart D. Barnscher

Subjects
Organic Chemistry, Clinical Biochemistry, Drug Discovery, Pharmaceutical Science, Molecular Medicine, Molecular Biology, Biochemistry
Published
2023
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4. Beyond the Rule of 5: Impact of PEGylation with Various Polymer Sizes on Pharmacokinetic Properties, Structure–Properties Relationships of mPEGylated Small Agonists of TGR5 Receptor

Author

Florence Leroux, Maxime Culot, Laura Butruille, Fabien Gosselet, Benoit Deprez, Rajaa Boulahjar, Julie Dumont, Mathieu Maingot, Geoffroy Dequirez, Vanessa Hoguet, Anne Tailleux, Manuel Lasalle, Nathalie Hennuyer, Oscar Chávez-Talavera, Isabelle Duplan, Julie Charton, Emmanuel Sevin, Catherine Piveteau, Bart Staels, Loic Belloy, Sophie Lestavel, Adrien Herledan, Alexandre Biela, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), We are grateful to the institutions that supported our laboratory: INSERM, Université de Lille, Institut Pasteur de Lille. This project was supported by Conseil Régional Nord-Pas de Calais, ERDF (convention no. 11003609), Etat DRRT, European Genomic Institute for Diabetes (EGID, ANR-10-LABX-46), the European Research Council (ERC Grant Immunobile, contract 694717), European Commission, INSERM, Université Lille 2 (Appel à projets 'orientations stratégiques': convention no. A007), and SATT Nord (M0075/SATTNORD), ANR (BABrain, convention n°ANR-17-CE14-0007-03), CPER CTRL17 FEDER TIIMaging. M.L. and V.H. are recipients of a doctoral fellowship of the French Ministère de la Recherche. NMR acquisitions were done at the Laboratoire d’Application de Résonance Magnétique Nucléaire (LARMN), Lille, France. B.S. is honorary member of the Institut Universitaire de France., ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), ANR-17-CE14-0007,BABrain,La signalisation des acides biliaires dans le cerveau et son rôle dans le contrôle métabolique(2017), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011)

Subjects
Agonist, Male, medicine.drug_class, Antibiotic resistance, [SDV]Life Sciences [q-bio], 01 natural sciences, Permeability, Polyethylene Glycols, Receptors, G-Protein-Coupled, 03 medical and health sciences, Mice, Structure-Activity Relationship, In vivo, Drug Discovery, PEG ratio, medicine, Animals, Humans, Hypoglycemic Agents, 030304 developmental biology, 0303 health sciences, Conjugate acid-base pairs, Chemistry, G protein-coupled bile acid receptor, 0104 chemical sciences, Mice, Inbred C57BL, 010404 medicinal & biomolecular chemistry, HEK293 Cells, Blood-Brain Barrier, Alcohols, PEGylation, Biophysics, Lipinski's rule of five, Microsomes, Liver, Molecular Medicine, Pharmacophore, Caco-2 Cells, Conjugate, Agonists
Abstract

International audience; PEGylation of therapeutic agents is known to improve the pharmacokinetic behavior of macromolecular drugs and nanoparticles. In this work, we performed the conjugation of polyethylene glycols (220-5000 Da) to a series of non-steroidal small agonists of the bile acids receptor TGR5. A suitable anchoring position on the agonist was identified to retain full agonistic potency with the conjugates. We describe herein an extensive structure-properties relationships study allowing us to finely describe the non-linear effects of the PEG length on the physicochemical as well as the in vitro and in vivo pharmacokinetic properties of these compounds. When appending a PEG of suitable length to the TGR5 pharmacophore, we were able to identify either systemic or gut lumen-restricted TGR5 agonists.

Published
2021
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5. Shaping the Future of Research: A perspective from early career researchers in Vancouver, Canada

Author

James M. McCoy, Azadeh HajiHosseini, Peter G. K. Clark, Jenny H. L. Chik, Manuel Lasalle, Brianne A. Kent, and Stefanie L. Vogt

Subjects
0301 basic medicine, ComputingMilieux_THECOMPUTINGPROFESSION, General Immunology and Microbiology, business.industry, Perspective (graphical), General Medicine, Public relations, General Biochemistry, Genetics and Molecular Biology, Session (web analytics), 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Mentorship, Political science, Science policy, Early career, General Pharmacology, Toxicology and Pharmaceutics, business, 030217 neurology & neurosurgery, Career development
Abstract

Future of Research is an organization dedicated to championing, engaging, and empowering early career researchers (ECRs). The organization was founded in 2014 and has since inspired other groups to advocate for a more equitable and sustainable research enterprise. Here we report the findings of the Future of Research Vancouver Symposium. The goals of the Vancouver symposium were to ascertain the perspective of ECRs in Canada and to outline pathways to a sustainable future for Canadian research. The symposium had two sessions. The first session was a series of talks that were intended to prepare attendees with an informed understanding of several perspectives in the science enterprise, with a particular focus on the Canadian system. The second session was a series of interactive workshops to identify the greatest challenges facing ECRs in Canada and to propose solutions. The results of the workshops illuminated three main themes for the challenges facing Canadian ECRs: funding, mentorship, and the divide between academia and other sectors. These themes are similar to those discussed at the Future of Research symposiums in the United States, emphasizing that these issues are not isolated to Canada; however, Canadian policies are trailing behind the progress being made in other countries.

Published
2018
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6. ChemInform Abstract: Access to Newly Functionalized Imidazole Derivatives: Efficient Synthesis of Novel 5-Amino-2-thioimidazoles Using Propylphosphonic Anhydride (®T3P)

Author

Pascal Roussel, Rajaa Boulahjar, Vanessa Hoguet, Benoit Deprez, Manuel Lasalle, Julie Charton, Jolien Van Obbergen, and Sylvain Picon

Subjects
chemistry.chemical_compound, Chemistry, Organic chemistry, Imidazole, General Medicine, Microwave assisted
Abstract

Various N-acetamidoisothioureas undergo microwave assisted T3P-mediated cyclodehydration to give imidazole derivatives.

Published
2015
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7. Access to newly functionalized imidazole derivatives: efficient synthesis of novel 5-amino-2-thioimidazoles using propylphosphonic anhydride (®T3P)

Author

Pascal Roussel, Manuel Lasalle, Jolien Van Obbergen, Sylvain Picon, Rajaa Boulahjar, Benoit Deprez, Vanessa Hoguet, Julie Charton, Biostructures et Decouverte de Medicament, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille

Subjects
010405 organic chemistry, Organic Chemistry, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, Combinatorial chemistry, 0104 chemical sciences, 3. Good health, chemistry.chemical_compound, chemistry, Block (telecommunications), Drug Discovery, Imidazole, Amine gas treating, ComputingMilieux_MISCELLANEOUS
Abstract

We describe here an efficient method to synthesize 5-amino-2-thioimidazole compounds by T3P-mediated cyclization of N -acetamidoisothiourea intermediates. The newly functionalized 5-amino-2-thioimidazole compounds are finally obtained in 5 steps from an amine as starting block.

Published
2015
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