Élisabeth Garanger, PhD November 10th 1977 (age 32) Laboratoire de Chimie des Polymères Organiques LCPO (UMR5629) - ENSCBP 16 Avenue Pey-Berland, 33607 Pessac Cedex, FRANCE Tel: +33 5 40 00 64 14 E-mail: email@example.com EDUCATION
2001 – 2005: PhD. in chemistry & biology (Joseph Fourier University, Grenoble,
2000 – 2001: MSc. degree in biological organic chemistry (Blaise Pascal
1997 – 2001: Chemical engineering degree (ENSCCF, Clermont-Ferrand, FR)
Specialization in fine and industrial organic chemistry
1995 – 1997: Preparatory to French chemical engineering schools (ENSCR, Rennes,
2009 – present: Laboratoire de chimie des polymères organiques, Institut Polytechnique de Bordeaux (Bordeaux, FR) Research fellow in Prof. S. Lecommandoux’s group
➤ Development of theranostic agents from block copolymer-based nanomaterials. Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School (Boston, MA, USA) Research fellow in Prof. L. Josephson’s group
➤ Development of a new class of multifunctional reagents. A strategy to access multifunctional nanomaterials, imaging probes, and sensors with high levels of complexity was devised to overcome limitations associated with current synthetic methods. "Multifunctional single-attachment-point" (MSAP) reagents, featuring multiple functional groups and a single chemically reactive group, were designed from a peptide scaffold. A series of MSAPs were synthesized to permit multimodal detection (fluorochromes, metal chelates, immunoreactive haptens), to modify nanomaterial properties (hydrophylic polymers), or to confer a therapeutic pharmacological activity (drugs). When an MSAP is reacted with a substrate (e.g. a nanoparticle, a protein, a small molecule), a complex multifunctional probe is obtained in a single step. The MSAP-based strategy was applied (i) to obtain multifunctional gold nanoparticles, (ii) to prepare a bioactive multifunctional protein for multimodal imaging of apoptosis, (iii) to study the localization in vivo of an integrin-targeting peptide, and (iv) to construct an hypervalent therapeutic antibody. ➤ Synthesis and biological evaluation of a MR contrast agent of cell death. A thiazole orange (TO) fluorochrome was modified and attached to a paramagnetic Gd chelate to obtain GadoTO, a bimodal probe which maintained the nucleic-acid binding property and the impermeability to healthy cells of TO. Interaction of GadoTO with plasmid DNA was studied by relaxometry and fluorescence. GadoTO was employed to image cell death by fluorescence (FACS, microscopy) and MR (cellular T relaxation times).
2001 – 2005: (31/2 years)Joseph Fourier University (Grenoble, FR)
PhD. graduate student co-supervised by Prof. P. Dumy (LEDSS, CNRS UMR 5616) and Prof. M.C. Favrot (Institut Albert Bonniot, INSERM U578)
➤ Design, synthesis and characterization of new targeting and vectorization systems in cancer Synthetic vectors targeting tumors and their associated neo-angiogenesis were synthesized and evaluated for drug delivery and molecular imaging applications. The vectors were devised to target the αVβ3 integrin receptor and to simultaneously carry either a cytotoxic cargo or a contrast-enhancing agent. The core of the vector was composed of a regioselectively addressable cyclic decapeptide scaffold (RAFT) presenting two distinct domains allowing the spatial separation of the targeting and delivery functions. The template was decorated with multiple copies of a cyclo[-RGDfK-] peptide through chemoselective oxime ligation. Conjugation of the vector with diverse detection molecules (biotin, fluorescein, cyanin) allowed its biological evaluation in vitro and in vivo. In vitro experiments revealed the tetrameric version to be the most potent in receptor- specific binding and cell internalization. The lead structure RAFT(c[-RGDfK-])4
proved to induce αVβ3 integrin clustering and to be internalized through a
receptor-mediated endocytosis. When administered systemically into immune deficient mice, (Cy5)RAFT(c[-RGDfK-])4 detected solid tumors as well as
disseminated metastases. The vector was further modified with cytotoxic molecules, including an antibacterial amphiphilic peptide, a chemotherapeutic drug or a toxin protein, which were linked through a disulfide bridge allowing their release into the targeted cells. Tumor-suppressing potencies were evaluated in vivo. The vector was also coupled to optical and nuclear imaging agents for the detection of deep tumors and metastases in mice.
Sanofi-Synthelabo (Sisteron, FR) Scientist in process chemistry in a R&D laboratory
➤ Adaptation of a two-step reaction of the manufacturing process of Irbesartan (Aprovel®) to the laboratory scale. Study of new organometallic routes.
1999 – 2000: (12 months)Aventis Animal Nutrition (Commentry, FR)
Scientist in pharmaceutical science and chemical engineering
➤ Development of a formulation of vitamins with suitable rumen stability. ➤ Quantification of solvent flows in manufacturing process.
Institute of Food Research (Norwich, UK) Associate scientist
➤ Characterization of the physicochemical properties of a complex polysaccharide protein (Caroubin) by NMR, FTIR, and SEM.
SPECIFIC SKILLS Chemistry Biology
◆ French: mother tongue ◆ English: fluent ◆ German: good notions ◆ Spanish: beginner LIST OF PUBLICATIONS
1/ E. Garanger, J.T. Blois, S.A. Hilderbrand, F. Shao, and L. Josephon; “Divergent
Oriented Syntheses for the design of reagents for protein conjugation”; J. Comb. Chem.; 2009; In press. 2/ D.E. Sosnovik, E. Garanger, E. Aikawa, M. Nahrendorf, J.L. Figuiredo, G.Dai, F.
Reynolds, A. Rosenzweig, R. Weissleder, and L. Josephon; “Molecular MRI of cardiomyocyte apoptosis with simultaneous delayed enhancement MRI distinguishes apoptotic and necrotic myocytes in vivo: Potential for midmyocardial salvage in acute ischemia”; Circulation : Cardiovascular Imaging; 2009; In press. 3/ E. Garanger, S.A. Hilderbrand, J.T. Blois, D.E. Sosnovik, R. Weissleder, and L.
Josephon; “A DNA-binding Gd chelate for the detection of cell death by MRI”; Chem. Commun.; 2009;(29); 4444-4446. 4/ L. Sancey, E. Garanger, S. Foillard, G. Schoehn, A. Hurbin, C. Albiges-Rizo, D.
Boturyn, C. Souchier, A. Grichine, P. Dumy, and J.L. Coll; “Clustering and internalization of integrin αvβ3 with a tetrameric RGD synthetic peptide”; Mol. Ther.; 2009;Vol. 17 (5); 837-843. 5/ E. Garanger, R. Weissleder, and L. Josephson; “A Multifunctional Single-
Attachment-Point Reagent for Controlled Protein Biotinylation”; Bioconjugate Chem.; 2009; Vol. 20 (1); 170-173. 6/ E. Garanger, E. Aikawa, F. Reynolds, R. Weissleder, and L. Josephson;
“Simplified syntheses of complex multifunctional nanomaterials”; Chem. Commun.; 2008; (39); 4792-4794. 7/ S. Foillard, Z.H. Jin, E. Garanger, D. Boturyn, M.C. Favrot, J.L. Coll, and P.
Dumy; “Synthesis and biological characterization of a targeted pro-apoptotic peptide”; ChemBioChem.; 2008; Vol. 9 (14); 2326-2332. 8/ E. Garanger, D. Boturyn, and P. Dumy; “Tumor targeting with RGD peptide
ligands - Design of new molecular conjugates for imaging and therapy of cancers”; Anticancer Agents Med. Chem.; 2007; Vol. 7 (5); 552-558. 9/ Z.H. Jin, V. Josserand, J. Razkin, E. Garanger, D. Boturyn, M.C. Favrot, P.
Dumy, and J.L. Coll; “Non-invasive optical imaging of ovarian metastases using Cy5-labeled RAFT-c(-RGDfK-)4”; Mol. Imaging; 2006; Vol. 5 (3); 188-197. 10/ E. Garanger, D. Boturyn, J.L. Coll, M.C. Favrot, and P. Dumy; “Multivalent RGD
synthetic peptides as potent αVβ3 integrin ligands”; Org. Biomol. Chem.; 2006; Vol. 4 (10); 1958-1965. 11/ E. Garanger, D. Boturyn, O. Renaudet, E. Defrancq, and P. Dumy;
“Chemoselectively addressable template: a valuable tool for the engineering of molecular conjugates”; J. Org. Chem.; 2006; Vol. 71 (6); 2402-2410. 12/ E. Garanger, D. Boturyn, Z.H. Jin, P. Dumy, M.C. Favrot, and J.L. Coll; “New
multifunctional molecular conjugate vector for targeting, imaging and therapy of tumors”; Mol. Ther.; 2005; Vol. 12 (6); 1168-1175. 13/ I. Texier, V. Josserand, E. Garanger, J. Razkin, Z.H. Jin, P. Dumy, M.C. Favrot,
D. Boturyn, and J.L. Coll; “Luminescent probes for optical in vivo imaging”;
Proceedings of SPIE: “Genetically Engineered and Optical Probes for Biomedical Applications III” D.J. Bornhop, S. Achilefu, R. Raghavachari, A.P. Savitsky Eds.; 2005; Vol. 5704; 16-23. 14/ D. Boturyn, J.L. Coll, E. Garanger, M.C. Favrot, and P. Dumy; “Template
assembled cyclopeptides as multimeric system for integrin targeting and endocytosis”; J. Am. Chem. Soc.; 2004; Vol. 126 (18); 5730-5739. 15/ Y. Wang, P.S. Belton, H. Bridon, E. Garanger, N. Wellner, M.L. Parker, A. Grant,
P. Feillet, and T.R. Noel; “Physicochemical studies of Caroubin: a Gluten-like protein”; J. Agr. Food Chem.; 2001; Vol. 49 (7); 3414-3419.
PATENTS 1/ L. Josephson, E. Garanger; “Methods and reagents for preparing multifunctional
probes”; MGH case # 3847; Pending patent application.
2/ L. Josephson, E. Garanger, S. Hilderbrand; “Vital fluorochrome-chelator probes
for imaging”; MGH case # 20312; Pending patent application.
LIST OF COMMUNICATIONS (ORAL O AND POSTERS P)
◆ Aquitaine Conferences / Polymers 2009 P - « Block copolymer-based nanoparticles for therapy and imaging of different types of cancer» Arcachon (FR), October 13-16th 2009. ◆ EICB Young Scientists’ Day O - « Multifunctional probes for multimodal molecular imaging » Bordeaux (FR), May 28th 2009. ◆ Meeting of the National Cancer Institute Alliance for Nanotechnology in Cancer P - « Simplifying the synthesis of complex multifunctional nanomaterials » Chicago (IL, USA), September 8-10th 2008. ◆ 236th ACS National Meeting & Exposition O - « Multifunctional Single-Attachment-Point reagents for probe design » Philadelphia (PA, USA), August 18th 2008. This communication has been reported and discussed in C&EN news, August 25th 2008, Vol. 86 (34). http://pubs.acs.org/cen/news/86/i34/8634notw2.html
◆ Mechanisms of Carrier-Mediated Intracellular Delivery of Therapeutics O - « Mechanism of interaction and internalisation of a multivalent RGD peptide carrier targeting the tumor-associated αVβ3 integrin » Montpellier (FR), August 26th 2005. ◆ 9ième Symposium de l’ICSN: « Cancer: targets, molecules and therapies » P - « Non-viral delivery of anti-angiogenic molecules for cancer imaging and treatment » Gif-sur-Yvette (FR), June 10-11th 2004. ◆ 8ième Colloque National d’Angiogenèse O - « Transfert ciblé non-viral de molécules anti-angiogeniques dans le cancer du poumon : efficacité thérapeutique et imagerie moléculaire » Annecy (FR), May 7th 2004. ◆ 10ièmes Rencontres de Chimie Organique Biologique O - « Conception, synthèse et caractérisation de nouveaux systèmes de guidage et de vectorisation pour la cancérologie » Aussois (FR), March 23rd 2004. ◆ European Society of Gene Therapy P - « Synthesis and characterization of a new multivalent RGD-based vector for in vivo drug delivery to tumors and for medical imaging » Edinburgh (UK), November 14-17th 2003.
◆ Groupe Français des Peptides et des Protéines P - « Conception, synthèse et caractérisation de nouveaux systèmes de guidage et de vectorisation pour la cancérologie » Anglet (FR), October 19-23rd 2003.
Diagnosis and therapy of tuberculous meningitis in childrenDepartment of Maternal and Pediatric Sciences, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,Via Commenda 9, 20122 Milan, ItalyChildren are among the subjects most frequently affected by tuberculous meningitis (TBM) due to theirrelative inability to contain primary Mycobacterium tuber
Faculty of Resource Science and Technology, UNIMAS This course is a continuation from the basic course, STB1083Biochemistry. This course is designed to cover topics in thebiochemical reactions within and between the cells that will bedescribe in details in this course. Products generated from thebiosynthesis of either amino acids, protein, carbohydrate, fattyacid or lipids are broken down f