SUMMARY
I am Loic Stefan, research scientist (chargé de recherche) at the National Center of Scientific Research (CNRS), working at the Laboratoire de Chimie Physique Macromoléculaire in Nancy since October 2016. I am specialized in biomimetic self-assembly processes based on DNA and peptide derivatives, from fundamental research and molecular design to applications. My current research interests are focused on two main areas:
Topic #1 – Development of innovative soft materials (hydrogels and organogels) based on peptides and peptide derivatives, able to self-assemble through specific supramolecular interactions. Thus, we design, synthesize, and study these systems following a multi-scale approach from the molecular/intermolecular (via NMR, FTIR, circular dichroism) to the mesoscopic/microscopic (via SAXS, NMR relaxometry, fluorescence, electron microscopy) and the macroscopic (via rheology) scales. Our aim is the understanding and the deciphering of the links between molecular structures <-> assembly process at different scales <-> resulting material properties. I just obtained a ANR JCJC “MUNCH” (2021-2024) focusing on multicomponent nucleopeptide-based hydrogels.
Topic #2 – Development of metal-binding peptide derivatives exhibiting antioxidant properties. Thus, we design, synthesize, and study peptide sequences able to chelate specific biologically active transition metals which play pivotal roles in the production of reactive oxygen species (ROS) leading, in fine, to oxidative stress. Up to now, we have focused our efforts on the chelation of Iron(III) with the development of peptides acting both as iron chelators and as free radical scavengers. This topic is in complete collaboration with Dr. Katalin Selmeczi, lecturer at L2CM (http://www.l2cm.univ-lorraine.fr/l2cm/annuaire/?pg=3) and is involved in the project IMPACT Biomolécules, Lorraine Université d’Excellence, "IronPepOx" (2019-2021).
ORCID: https://orcid.org/0000-0001-8517-5982
RESUME
2010-2013: After a master’s degree in Molecular Chemistry and Green Process, I joined the Institut de Chimie Moléculaire de l’Université de Bourgogne (Dijon, France) for a Ph.D. thesis, funded by the CNRS (thèse BDI), under the supervision of Dr. David Monchaud. All along these years, I worked in a very pluridisciplinary project, from chemistry to biophysics and biology, focused on the studies of non-canonical DNA/RNA structures and, mainly, on the synthesis, biophysical and physicochemical studies and applications of water-soluble template-assembled G-quartets (TASQ). These innovative molecules were both used as DNA ligands in an anticancer research context and in the nanotechnology field with unprecedented peroxidase-like properties.
2013-2016: Then, I moved to Politecnico di Milano (Milan, Italy), involved in an ERC project (Foldhalo) in the group of Pr. Pierangelo Metrangolo. My work was focused on the impact of halogenation on peptide and protein self-assemblies in both biological contexts (e.g., oxidative stress) and biotechnology (mainly in the formation of soft materials). In 2014, I obtained the Polimi International Fellowship for 18 months to pursue my research in the same group.
2016-today: Research Scientist (chargé de recherche) at the National Center of Scientific Research (CNRS), working at the Laboratoire de Chimie Physique Macromoléculaire in Nancy, France.
PEOPLE
Current:
- Paul Hoschtettler (Ph.D student, Jan. 2021 – Dec. 2023) on topic #1: research and development of multicomponent nucleopeptide-based hydrogels. Funded by the Agence Nationale de la Recherche (ANR, project MUNCH).
Former:
- Maria Victoria Andrade Gomez (M2 student (ENSIC, Univ. Lorraine), Jan. 2023 - July 2023) on topic #1: research and development of multicomponent nucleopeptide-based hydrogels. Funded by the Agence Nationale de la Recherche (ANR, project MUNCH).
- Marine Koch (M2 student (CPM, Univ. Lorraine), Jan. 2022 - July 2022) on topic #1: research and development of multicomponent nucleopeptide-based hydrogels. Funded by the Agence Nationale de la Recherche (ANR, project MUNCH).
- Dr. Tristan Giraud (Ph. D student, Oct. 2018- Dec. 2021) on topic #1: research and development of innovative nucleopeptide-based hydrogels. Funded by the Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation (MESRI).
- Dr. Gizella Csire (Post-doc, Mar. 2019 – Nov. 2020) on topic #2 : Iron(III)-chelating model peptides as bioinspired antioxidants. Funded by LUE Biomolécules/ANR (project IronPepOx).
- Dr. Anne-Charlotte Dandin (Chemical Engineer and Pharmacist, Jan. 2017 – Oct. 2018) did her Pharmacy Thesis under my supervision and Dr. David Gilot (Univ. Rennes I). Title: Hydrogels peptidiques pour la culture de cellules souches: état de l’art, applications et perspectives.
- Lynda Saidi (Master student, Feb. 2020- Jul. 2020) on topic #2 : development of Iron(III)-chelating peptides. Funded by the LUE Biomolécules/ANR (project ImPliCit).
- other students doing their internship in the lab: from BTS Chimie Lycée Louis Vincent, Metz (8 weeks): Kenza Koukebene (2019), Ophélie Mathiez (2018), Lucie Lejeune and Amélie Berthelin (2017); from ENSIC, Chemical Engineering Students, Nancy (8 weeks): Bairu Huo and Nathalia Rovira Gomez (2018).
Our collaborations:
♦ On topic #1:
- Dr. Philippe Marchal, LRGP, UMR7274 (Nancy, France - link).
- Pr. Sabine Bouguet-Bonnet, CRM2, UMR7036 (Nancy, France - link).
- Dr. Marie-José Stébé, IJB (Nancy, France).
♦ On topic #2:
- Dr. Katalin Selmeczi, L2CM, UMR7053 (Nancy, France)
- Dr. Laetitia Canabady-Rochelle, LRGP, UMR7274 (Nancy, France - link).
FUNDINGS
- ANR JCJC “MUNCH”: Multicomponent Nucleopeptide-based Hydrogels (Jan. 2021- Jul. 2024, 233 k€, topic #1) – coordinator.
- Fédération Jacques Villermaux - Pôle EMPP Projets investissements jeunes chercheurs: (Apr. 2021, 10 k€) - coordinator.
- Impact LUE Biomolécules “IronPepOX”: Iron(III)-chelating model peptides as bioinspired antioxidants (Feb. 2019 – Mar. 2021, 100 k€) – coordinator.
- Fédération Jacques Villermaux - Pôle EMPP “SARGel”: (Mar. 2019, 12.9 k€) - coordinator.
- Impact LUE Biomolécules “ImPliCit”: Elucidation of mechanisms of metal ion-peptide interactions: Understand to innovate (Feb. 2018 – Dec. 2018, 10 k€) – participant.
- Institut Carnot ICEEL “NHyCCS”: Nouveaux milieux hydrogels pour la culture de cellules souches (Jan. 2018- Dec. 2018, 10 k€) – coordinator.
- Fédération Jacques Villermaux “GELISOU” (Sept. 2017 – Nov. 2017, 5 k€) – coordinator.
INTERNATIONAL PEER-REVIEWED PUBLICATIONS
40 - "Deciphering interactions involved in Immobilized Metal ion Affinity Chromatography and Surface Plasmon Resonance for validating the analogy between both rechnologies", R. Irankunda, J. Camano Echavarria, C. Paris, K. Selmeczi, L. Stefan, S. Boschi-Muller, L. Muhr, L. Canabady-Rochelle, Inorganics, 2024, accepted
39 - "Preparation and optimization of agarose or polyacrylamide/amino acid-based double network hydrogels for photocontrolled drug release", S. Xiang, C. Guilbaud-Chéreau, P. Hoschtettler, L. Stefan, A. Bianco, C. Ménard-Moyon, Int. J. Biol. Macromol., 2024, 127919. htpps://doi.org/10.1016/j.ijbiomac.2023.127919
38 - "Gelatin Methacryloyl (GelMA) Hydrogel Scaffolds: Predicting Physical Properties Using an Experimental Design Approach", C. Peyret, K. Elkhoury, S. Bouguet-Bonnet, S. Poinsignon, C. Boulogne, T. Giraud, L. Stefan, Y. Tahri, L. Sanchez-Gonzalez, M. Linder, A. Tamayol, C.J.F. Kahn, E. Arab-Tehrany, Int. J. Molecular Sci., 2023, 24, 13359. https://doi.org/10.3390/ijms241713359
37 - “Highly Synergistic Properties of Multicomponent Hydrogels Thanks to Cooperative Nucleopeptide Assemblies", P. Hoschtettler, G. Pickaert, A. Carvalho, M.-C. Averlant-Petit, L. Stefan, Chem. Mater., 2023, 35, 4259. http://doi.org/10.1021/acs.chemmater.3c00308.
36 - “A lysine-based 2:1-[α/aza]-pseudopeptide series used as additives in polymeric membranes for CO2 capture: synthesis, structural studies, and application", M. I. A. Ibrahim, X. Solimando, L. Stefan, G. Pickaert, J. Babin, C. Arnal-Herault, D. Roizard, A. Joncquières, J. Bodiguel, M.-C. Averlant-Petit, RSC Advances, 2023, 13, 10051. http://doi.org/10.1039/D3RA00409K.
35 - “Metal-chelating activity of soy and pea protein hydrolysates obtained after different enzymatic treatments from protein isolates", S. El Hajj, R. Irankunda, J. A. Camano Echavarria, P. Arnoux, C. Paris, L. Stefan, C. Gaucher, S. Boschi-Muller, L. Canabady-Rochelle, Food Chemistry, 2023, 405, 134788 . http://doi.org/10.1016/j.foodchem.2022.134788.
34 - “Metal-chelating peptides separation using immobilized metal ion affinity chromatography: experimental methodology and simulation", R. Irankunda, J. A. Camano Echavarria, C. Paris, L. Stefan, S. Desobry, K. Selmeczi, L. Muhr, L. Canabady-Rochele, Separations, 2022, 9, 370. http://doi.org/10.3390/separations9110370 -- Selected as Editor's choice
33 - “On the Observation of 14N Quadrupole Resonance Transitions in Water Proton NMR Relaxometry Dispersion Curves: The Case of a Labile NH Grouping in a Semirigid Molecular Moiety", S. Bouguet-Bonnet, T. Giraud, L. Stefan, M.-C. Averlant-Petit, D. Canet, J. Phys. Chem. B., 2022, 126, 37. http://doi.org/10.1021/acs.jpcb.2c05208.
32 - "Emerging low-molecular weight nucleopeptide-based hydrogels: state of the art, applications, challenges and perspectives", T. Giraud, P. Hoschtettler, G. Pickaert, M.-C. Averlant-Petit, L. Stefan,* Nanoscale, 2022, 14, 4908. http://doi.org/10.1039/d1nr06131c -- Selected for the special issue "Nanoscale 2022 Emerging Investigators" (link)
31 - “Bio-inspired casein-derived antioxidant peptides exhibiting a dual direct/indirect mode of action", G. Csire, F. Dupire, L. Canabady-Rochelle, K. Selmeczi,* L. Stefan,* Inorg. Chem., 2022, 61, 1941. http://doi.org/10.1021/acs.inorgchem.1c03085
30 - “Electrically switchable nanolever technology for the screening of metal-chelating peptides in hydrolysates", S. El Hajj, C. T. Sepulveda Rincon, J.-M. Girardet, C. Cakir-Kiefer, L. Stefan, J. E. Zapata Montoya, S. Boschi-Muller, C. Gaucher, L. Canabady-Rochelle, J. Agri. Food Chem., 2021, 36, 8819. http://doi.org/10.1021/acs.jafc.1c02199
29 - “Co-assembly and multicomponent hydrogel formation upon mixing nucleobase-containing peptides", T. Giraud, S. Bouguet-Bonnet, M.-J. Stébé, Lionel Richaudeau, G. Pickaert, M.-C. Averlant-Petit, L. Stefan,* Nanoscale, 2021, 13, 10566. http://doi.org/10.1039/d1nr02417e.
28 - “Rheological investigation of the influence of dextran on the self-assembly of lysine derivatives in water/dimethylsulfoxide mixtures", G. Rangel Euzcateguy, C. Parajua-Sejil, P. Marchal, D. Chapron, M.-C. Averlant-Petit, L. Stefan, G. Pickaert, A. Durand, Colloids Surf., A Physicochem. Eng Asp., 2021, 625, 126908. http://doi.org/10.1016/j.colsurfa.2021.126908
27 - “Rheological investigation of supramolecular physical gels in water/dimethylsulfoxide mixtures by lysine derivatives”, G. Rangel Euzcateguy, C. Parajua-Sejil, P. Marchal, D. Chapron, M.-C. Averlant-Petit, L. Stefan, G. Pickaert, A. Durand, Polymer International, 2021, 70, 256. http://doi.org/10.1002/pi.6179.
26 - “Metabolomic approach based on LC-HRMS for the fast screening of iron(II)-chelating peptides in protein hydrolysates”, C. Paris, K. Selmeczi, B. Ebel, L. Stefan, G. Csire, C. Cakir-Kiefer, S. Desobry, L. Canabady-Rochelle, P. Chaimbault, Anal. Bioanal. Chem., 2021, 413, 315. http://doi.org/10.1007/s00216-020-03037-1.
25 - “Application in Nutrition: Mineral-Binding” (book chapter) S. El Hajj., T. Sepulveda-Rincon, C. Paris, T. Giraud, G. Csire, L. Stefan, K. Selmeczi, J.-M. Girardet, S. Desobry, S. Bouhallab, L. Muhr, C. Gaucher, L. Canabady-Rochelle, Biologically Active Peptides (Ed. J. Wu and F. Toldra), Elsevier Book, 2020, in press.
24 - “Cyclohexamer [-(D-Phe-azaPhe-Ala)2-]: good candidate to formulate supramolecular organogels”, I. Mohamed Ibrahim Abdelmoneim, G. Pickaert, L. Stefan, B. Jamart-Gregoire, J. Bodiguel, M.-C. Averlant-Petit, RSC Advances, 2020, 10, 43859. http://doi.org/10.1039/d0ra07775e.
23 - “Improving and fine-tuning the properties of peptide-based hydrogels via incorporation of peptide nucleic acids”, T. Giraud, S. Bouguet-Bonnet, P. Marchal, G. Pickaert, M.-C. Averlant-Petit, L. Stefan,* Nanoscale, 2020, 12, 19905. http://doi.org/10.1039/D0NR03483E
22 - “Both metal-chelating and free radical-scavenging synthetic pentapeptides as efficient inhibitors of reactive oxygen species generation”, G. Csire, L. Canabady-Rochelle, M.-C. Averlant-Petit, K. Selmeczi,* L. Stefan,* Metallomics, 2020, 12, 1220. http://doi.org/10.1039/d0mt00103a
21 - “Applications of guanine quartets in nanotechnology and chemical biology”, L. Stefan,* D. Monchaud,* Nature Reviews Chemistry, 2019, 3, 650. http://doi.org/10.1038/s41570-019-0132-0
20 - “New C-terminal hydrazide L-Leucine derivatives as multi-solvent low molecular weight organogelators”, M. M. Abdellatif, M.-C. Averlant-Petit, L. Stefan, G. Pickaert, Journal of Textiles, Coloration and Polymer Science, 2018, 15, 73. http://doi.org/10.21608/jtcps.2018.5976.1011
19 - “Amino acids modifications to improve and fine-tune peptide-based hydrogels” (book chapter), L. Stefan,* Amino Acids – New Insights and Roles in Plant and Animal (Ed. T. Asao and Md. Asaduzzaman), Intech, 2017 (ISBN 978-953-51-3242-4). http://doi.org/10.5772/intechopen.68705
18 - “Native and synthetic G-quartet-based DNAzyme systems: artificial enzymes for biotechnological applications” (book chapter), L. Stefan,* Advanced Catalytic Materials (Ed. L. E. Norena-Franco), Intech, 2016 (ISBN 978-953-51-4596-7). http://doi.org/10.5772/62165
17 - “Synthetic G-quartets as versatile nanotools for the luminescent detection of G-quadruplexes”, A. Laguerre, M. Levillain, L. Stefan, R. Haudecoeur, F. Katranji, M. Pirrotta, D. Monchaud, Chimia, 2015, 69, 530. http://doi.org/10.2533/chimia.2015.530
16 - “Nature-inspired strategies to target DNA/RNA-quadruplexes” (book chapter), A. Laguerre, L. Stefan, D. Monchaud, Biological relevance & therapeutic applications of DNA- and RNA-quadruplexes (Ed. D. Monchaud), Future Science (UK), 2015, p206-217. http://doi.org/10.4155/fseb12013.13.50
15 - “Supramolecular amplification of amyloid self-assembly by iodination”, A. Bertolani, L. Pirrie, L. Stefan, N. Houbenov, J. S. Haataja, R. Milani, O. Ikkala, G. Resnati, P. Metrangolo, Nature Commun., 2015, 6, 7574. http://doi.org/10.1038/ncomms8574
14 - “A twice-as-smart synthetic G-quartet: PyroTASQ is both a smart quadruplex ligand and a smart fluorescent probe”, A. Laguerre, L. Stefan, M. Larrouy, D. Genest, J. Novotna, M. Pirrotta, D. Monchaud, J. Am. Chem. Soc., 2014, 136, 12406. http://doi.org/10.1021/ja506331x
13 - “Porphyrin-based design of bioinspired multi-target quadruplex ligands”, A. Laguerre, N. Desbois, L. Stefan, P. Richard, C. P. Gros, D. Monchaud, ChemMedChem, 2014, 9, 2035. http://doi.org/10.1002/cmdc.201300526
12 - “Caffeine-based gold(I) N-heterocyclic carbenes as possible anticancer agents: synthesis and biological properties”, B. Bertrand, L. Stefan, M. Pirrotta, D. Monchaud, E. Bodio, P. Richard, P. Le Gendre, E. Warmerdam, de M. Jager, G. Groothuis, M. Picquet, A. Casini, Inorg. Chem., 2014, 53, 2296. http://doi.org/10.1021/ic403011h
11 - “Surface-immobilized DNAzyme-type biocatalysis”, L. Stefan, T. Lavergne, N. Spinelli, E. Defrancq, D. Monchaud, Nanoscale, 2014, 6, 2693. http://doi.org/10.1039/C3NR05954E
10 - “Multitasking water-soluble synthetic G-quartets: from preferential RNA-quadruplex interactions to biocatalytic activity”, R. Haudecoeur, L. Stefan, D. Monchaud, Chem. Eur. J., 2013, 19, 12739. http://doi.org/10.1002/chem.201300791
9 - “Closer to nature: a ATP-dependent bioinspired catalytic oxidation process”, L. Stefan, D. Duret, N. Spinelli, E. Defrancq, D. Monchaud, Chem. Commun., 2013, 49, 1500. http://doi.org/10.1039/C2CC38317A
8 - “A model of smart G-quadruplex ligand”, R. Haudecoeur, L. Stefan, F. Denat, D. Monchaud, J. Am. Chem. Soc., 2013, 135, 550. Recommended by the “faculty of 1000”. http://doi.org/10.1021/ja310056y
7 - “Assessing the differential affinity of small molecules for noncanonical DNA structures”, L. Stefan, B. Bertrand, P. Richard, P. Le Gendre, F. Denat, M. Picquet, D. Monchaud, ChemBioChem, 2012, 13, 1905. http://doi.org/10.1002/cbic.201200396
6 - “Insights into how nucleoside supplements enhance the peroxidase-mimicking DNAzyme activity of the G-quadruplex/hemin system”, L. Stefan, F. Denat, D. Monchaud, Nucleic Acids Res., 2012, 40, 8759. http://doi.org/10.1093/nar/gks581
5 - “Porphyrin-templated synthetic G-quartet (PorphySQ): a second prototype of G-quartet based G-quadruplex ligand”, H.-J. Xu, L. Stefan, R. Haudecoeur, S. Vuong, P. Richard, F. Denat, J.-M. Barbe, C. P. Gros, D. Monchaud, Org. Biomol. Chem., 2012, 10, 5212. http://doi.org/10.1039/C2OB25601K
4 - “Identifying three-way DNA junction-specific small-molecules”, S. Vuong, L. Stefan, P. Lejault, Y. Rousselin, F. Denat, D. Monchaud, Biochimie, 2012, 94, 442. http://doi.org/10.1016/j.biochi.2011.08.012
3 - “Deciphering the DNAzyme activity of multimeric quadruplexes: insights into their actual role in the telomerase activity evaluation assay”, L. Stefan, F. Denat, D. Monchaud, J. Am. Chem. Soc., 2011, 133, 20405. http://doi.org/10.1021/ja208145d
2 - “Harnessing nature’s insights: synthetic small molecules with peroxidase-mimicking DNAzyme properties”, L. Stefan, H.-J. Xu, C. P. Gros, F. Denat, D. Monchaud, Chem. Eur. J., 2011, 17, 10857. http://doi.org/10.1002/chem.201101337
1 - “DOTASQ as a prototype of nature-inspired G-quadruplex ligand”, L. Stefan, A. Guédin, S. Amrane, N. Smith, F. Denat, J.-L. Mergny, D. Monchaud, Chem. Commun., 2011, 47, 4992. http://doi.org/10.1039/C0CC04960C
FELLOWSHIPS and AWARDS
2016-2019: Prime d'encadrement doctoral et de recherche (PEDR)
2014-2016: Politecnico di Milano International Fellowship (50 k€)
2015: French Chemical Society thesis prize (organic chemistry section)
2013: Participation at the 63rd Lindau Nobel Laureates Meeting (selected by CNRS)
2013: Best oral presentation award (14th days of the Carnot-Pasteur doctoral school)
2013: Best oral presentation award (20th days of the Young researchers of the French Medicinal Chemistry Society)
2010 : CNRS Ph.D. fellowship (Bourse Docteur Ingénieur)
MISCELLANEOUS
Memberships: Société Chimique de France and the Groupe Français des Peptides et Protéines.
Institutional responsibilities: Elected Member at the University Research Center “Energy, Mechanics, Processes and Products” (Pôle Scientifique EMPP, http://empp.univ-lorraine.fr/) – 2017-2022.
Organization of scientific meetings:
- Member of the organizing steering committee for the International Conference on Metal-Binding Peptides: methodologies and applications (July 2020 - postponed, >250 attendees expected). Nancy, France. http://mbp2020-nancy.com/
- Organization of the laboratory seminars BlaBlaScience.
Reviewer for International Scientific Journals, including RSC Chemical Science, Chemistry A European Journal, RSC Advances, Nucleosides, Nucleotides and Nucleic Acids, Journal of Zhejiang University-Science B.