Team
Endocytic Trafficking and Intracellular Delivery
Presentation
Staff scientists and staff research engineers of the Endocytic Trafficking and Intracellular Delivery team:
Ludger Johannes (ludger.johannes@curie.fr, +33 1-56246351)
Massiullah Shafaq-Zadah (massiullah.shafaq-zadah@curie.fr, +33 1-56246352)
Christian Wunder (christian.wunder@curie.fr, +33 1-56246358)
Estelle Dransart (estelle.dransart@curie.fr, +33 1-56246352)
Caio Vaz Rimoli (caio.vaz-rimoli@curie.fr, +33 1-56246358)
For all other team members, see Members.
Research in the Endocytic Trafficking and Intracellular Delivery team focuses on the mechanisms by which glycans regulate the cell surface dynamics of plasma membrane proteins and their polarized intracellular distribution, and mediate the cellular entry of pathogens. We further harness these principles to develop intracellular delivery strategies for immunotherapy.
Endocytosis allows for the internalization of extracellular materials and cell surface receptors, using membrane-bound carriers. Our team discovered a mechanism by which tubular endocytic pits are generated through the interaction of oligomeric lectins with glycans on a specific class of glycosylated lipids, the glycosphingolipids (GSLs)(1,2). Pathogenic lectins exploit this mechanism to drive the GSL-dependent uptake of bacterial toxins (e.g., Shiga toxin and cholera toxin) and animal viruses (e.g., polyomaviruses)(3). Endogenous lectins, known as galectins, in turn mediate the GSL-dependent internalization of glycoprotein cargos, including cell adhesion molecules (e.g., integrins, CD44) and scavenger receptors (e.g., LRP1)(4). In both cases, cargo uptake proceeds independently of the canonical clathrin-mediated endocytic machinery. We coined the term GlycoLipid–Lectin (GL-Lect) driven endocytosis to describe this distinct uptake process (5, Figure1).
Research themes
A first major focus of our current research is on the elucidation of structural, molecular, and pathophysiological principles governing GL-Lect driven endocytosis, with a particular emphasis on polarized trafficking across intestinal enterocytes, epithelial–mesenchymal plasticity in breast cancer, and immune checkpoints in head and neck squamous cell carcinoma (HNSCC). To address these questions, we combine state-of-the-art imaging approaches, including lattice light-sheet microscopy (6, 7, 8), fluorescence orientation microscopy, and spectral imaging, with membrane protein reconstitution (9, 10), cryogenic electron microscopy (6), DNA origami (11), multi-omics analyses, organoid systems, and genetically engineered mouse models.
A second major focus of our research program is chemical biology. We identify small-molecule modulators of GSL metabolism as candidate therapeutics for lysosomal storage disorders. We define their cellular targets, elucidate their molecular and cellular mechanisms of action, and evaluate their therapeutic efficacy in mouse models of disease. In parallel, we develop synthetic chemical tools to reconstitute and functionally interrogate GSLs in physiological and pathological contexts, with particular emphasis on cancer and immunity. We have successfully used a similar approach in the past to find small-molecule modulators of bacterial toxin trafficking and intoxication (see Figure 2).
A third major research direction exploits GSL ligands to promote the targeted intracellular delivery of antigenic peptides and proteins to professional antigen-presenting cells, namely dendritic cells. Our goal is to induce immune modulation at mucosal surfaces, enabling preventive and durable vaccination against infectious diseases, such as COVID-19, as well as therapeutic vaccination against mucosal malignancies, including lung cancer and gastric cancer. To this end, we develop both mRNA- and protein subunit-based vaccine platforms, including the chemical synthesis of our dendritic cell-targeting vector STxB, a 69-amino-acid protein that we assemble in vitro into its homopentameric structure.
Members
Publications
Trends in Cell Biology - 01/04/2026
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Nature Communications - 27/10/2025
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Nature Cell Biology - 01/03/2025
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Nature Communications - 08/11/2024
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Molecular Cancer Therapeutics - 01/04/2022
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Angewandte Chemie International Edition - 25/06/2021
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Nature Communications - 01/12/2021
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Communications Biology - 01/12/2021
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Nature Chemical Biology - 01/03/2020
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Cell - 01/06/2017
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Nature Nanotechnology - 01/12/2016
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Cell - 01/08/2016
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Nature Cell Biology - 01/01/2016
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Nature - 22/01/2015
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Nature Cell Biology - 01/06/2014
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Cell - 01/04/2010
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Cell - 01/02/2010
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Nature Cell Biology - 01/01/2010
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Cancer Research - 01/01/2013
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Nature - 29/11/2007
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Developmental Cell - 01/04/2004
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Life of the team
Our prizes and patents
Our patents
Billet A, Schmidt F, Johannes L, Servent D, MOURIER G, ... 2026. Methods of producing Shiga toxin B-subunit (STxB) monomers and oligomers, and uses thereof. US Patent 12,527,854
Johannes L, Billet A, Ulmer J, Servent D, G MOURIER, P KESSLER, .... 2024. Functionalized Shiga Toxin B-Subunit (STxB) proteins and conjugates thereof. US Patent App. 18/255,462
T Murarasu, F Perez, L Johannes. 2021. Peptides, especially polypeptides, phage display screening method and associated means, and their uses for research and biomedical applications. US Patent App. 16/606,494
L Johannes, E Tartour, B Goud, WH Fridman. 2017. Universal carrier for targeting molecules to GB3 receptor expressing cells. US Patent 9,603,923
E Tartour, L Johannes. 2017. Compositions having means for targeting at least one antigen to dendritic cells. US Patent App. 15/223,3232024,
Johannes L, and Murarsu T. 2017. Peptides, peptide library screening and uses for research and biomedical applications. European Patent EP17305454.5 filed on April 20, 2017, and PCT/EP2018/056311, filed on March 13, 2018; under contract with OGD2 Pharma (2017-ongoing).
Johannes L, Deutsch E, and Tartour E. 2014. Combined vaccination / radiotherapy for cancer treatment. European Patent EP20150000507 / WO2016134838A1.
Gillet D, Barbier J, Johannes L, Cintrat JC, and Noël R. 2012. Nouveaux composés ayant une activité protectrice vis-à-vis de l’action de toxines au mode d’action intracellulaire. European patent filed on October 19, 2012 (EP12306297, US9540356B2).
Johannes L. 2012. Conjugates of the B subunit of Shiga toxin for use as contrasting agents for imaging and therapy. European Patent EP12306524.5, WO2014086942A1.
Johannes L. 2012. Conjugates of the B subunit of Shiga toxin for anticancer therapies. European Patent EP12306521.1; option agreement with Remora Partners (2015-ongoing).
Tartour E, Johannes L. 2011. Compositions having means for targeting at least one antigen to dendritic cells. European patent (EP11305959.6, WO2013014128A1); licensed to STxB Pharma Technologies Inc (2012-2014); option agreement with Remora Partners (2015-ongoing).
Gillet D, Barbier J, Johannes L, Stechmann B, and Bai SK. 2009. Inhibitors of the Shiga toxin trafficking through the retrograde pathway. European patent (EP 2296757 A2, WO2009153665A2).
Johannes L, Florent JC, Schmidt F, El Alaoui A, Decaudin D, and Robine S. 2007. Shiga toxin B-subunit/Chemotherapeutics conjugates. US patent filed on December 18, 2007 (US 11 958 576); licensed to ShigaMediX (2007-2010), STxB Pharma Technologies Inc (2012-2014).
Tartour E, Johannes L, Fridman WH, Freyburger L, Adotevi O, and Vingert V. 2006. Compositions using the B-subunit of Shiga toxin as a means of stimulating NKT cells. European patent filed on December 28, 2006 (EP 06 292 066.5); licensed to ShigaMediX (2006-2010), STxB Pharma Technologies Inc (2012-2014); option agreement with Remora Partners (2015-ongoing).
Johannes L, Florent JC, Grierson D, Maillard P, Robine S, and Roger J. 2002. Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to Gb3 expressing tumors. European patent filed on August 2, 2002 (EP 02 291 965.5); delivered in the US, Europe, Japan; licensed to STxB Pharma Technologies Inc (2012-2014); option agreement in siRNA field with Cenix Biosciences (2010-2013).
Johannes L, Goud B, Fridman WH, Tartour E, Florent JC. 2001. Universal carrier for targeting molecules to Gb3 receptor expressing cells. European patent filed on February 1st, 2001; worldwide extension (WO 02/060937); delivered in the US, Europe, Japan; licensed to Select Therapeutic Inc (2001), ShigaMediX (2005-2010), STxB Pharma Technologies Inc (2012-2014); option agreement in siRNA field with Cenix Biosciences (2010-2013); option agreement with Remora Partners (2015-ongoing).
Green A, Johannes L, Goud B, Tartour E, Fridman WH. 1998. Verotoxin B-subunit for immunization. Patent EP 99 923 063,4; delivered in Europe; licensed to Select Therapeutic Inc (1998-2001), ShigaMediX (2005-2010), STxB Pharma Technologies Inc (2012-2014); option agreement in siRNA field with Cenix Biosciences (2010-2013); option agreement with Remora Partners (2015-ongoing).
Johannes L, Goud B, Tartour E, Friedman WH. 1997. Chimeric polypeptide comprising the fragment B of Shiga toxin and peptides of therapeutic interest. Filed in France on July 18, 1997; worldwide extension on July 17, 1999 (WO99/03881); delivered in the US, Europe, Hong-Kong, Japan; licensed to Select Therapeutic Inc (1998-2001), ShigaMediX (2005-2010), STxB Pharma Technologies Inc (2012-2014); option agreement in siRNA field with Cenix Biosciences (2010-2013); option agreement with Remora Partners (2015-ongoing).
Prize and Distinctions
2019 to today Elected member of the German National Academy of Sciences — Leopoldina
2014 to 2020 European Research Council (ERC) advanced grant
2012 to today Elected member of the European Molecular Biology Organization (EMBO)
2011 to 2015 Prime d’excellence scientifique INSERM
2004 Laureate of company creation program ANVAR
1995 to 1997 BASF Forschungsprogramm Post-Doc Grant Program
1993 to today Boehringer Ingelheim Fonds PhD grant and alumni membership
1988 to today Studienstiftung des deutschen Volkes (German sponsorship organization for the academically gifted, promoting excellence, funding, scholars)
Ludger Johannes has been elected as member of the Leopoldina, German National Science Academy. He has joined the Genetics/Molecular Biology and Cell Biology section. Leopoldina is the world’s oldest academy involved in natural sciences; its members are distinguished scientists from all over the world.
Alumni
Alumni
Alumni list
Ranjit Gulvady (India): Post-doc, 2024-2025 (afterwards: Stable position at EarlyScreenDx, India)
Debarpan Ghosh (India): PhD, 2020-2024 (afterwards: Post-doc in Andres Lebensohn's team at NCI (Bethesda, USA))
Ewan MacDonald (UK): Post-doc, 2018-2023 (afterwards: CRCN INSERM stable scientist position)
Justine Hadjerci (France): Master 2, then PhD, 2020-2023 (afterwards: Stable position as Protein Biochemist Scientist at Alaya.bio)
Alexis Pinet (France): Post-doc, 2022-2023 (afterwards: Position at Bandpay & Greuter, France)
Alison Forrester (UK): Post-doc, 2017-2022 (afterwards: Lifetime position at Belgium Fund for Scientific Research – FNRS, team leader)
Harikrishna Bavireddi (India): Post-doc, 2018-2022
Anne Billet (France): Master 2, then PhD, 2017-2021 (afterwards: MBA at Collège des Ingénieurs, Paris, then stable position as Scientific Analyst, Elaia investment fund)
Julio Sampaio (Portugal): Post-doc, 2017-2020 (afterwards: Position as head of metabolomics / lipidomics platform at Institut Curie)
Bhanudas Dasari (India): Post-doc, 2016-2020 (afterwards: Post-doc with Adam Nelson, University of Leeds)
Thomas Murarasu (France): PhD, then Post-doc, 2014-2020 (afterwards: Stable position at OGD2 Pharma, France)
Alena Ivashenka (Belarus): PhD, 2016-2019 (afterwards: Post-doc with Dolores Hambardzumyan (Icahn School of Medicine at Mount Sinai, USA))
Marco Lucchino (Italy): PhD, 2015-2019 (afterwards: MBA at SDA Bocconi School of Management (Italy), stable positions at Alira Health, then Global Value & Access Manager at Servier, France)
Cesar Augusto Valades-Cruz (Mexico): Post-doc, 2016-2019 (afterwards: Post-doc at INRIA, Rennes, France; Researcher at …. Wuhan, China)
Joanna Zell (UK): PhD, 2015-2018 (afterwards: Post-doc with David Monchaud (France), then stable position at Bayer in Lyon (France))
Dhiraj Bhatia (India): Post-doc, 2013-018 (afterwards: Team leader at IIT Gandhinagar, India)
Stefan Rathjen (Germany): PhD, 2014-2017 (afterwards: Stable position at Silence Therapeutics (Germany))
Bibhuti Bhjusan Parcida (India): Post-doc, 2014-2016 (afterwards: Assistant Professor, IIT-Bhubaneswar, India)
Senthil Arumugam (India): Post-doc, 2013-2016 (afterwards: Team leader at University of New South Wales, then Team leader at Monash University, Australia)
Haifei Gao (China): PhD, 2011-2015 (afterwards: Post-doc with Patrick Midoux, Orléans (France))
Ulrike Becken (Germany): Post-Doc, 2011-2015 (afterwards: Position at Eppendorf, Germany)
Henri-François Renard (Belgium): Post-Doc, 2011-2015 (afterwards: Professor and team leader at Université de Namur, Belgium)
Maria Daniela Garcia-Castillo (USA): PhD, 2010-2014 (afterwards: Post-doc with Wayne Lencer (USA), then stable position at Eli Lilly and Company in Indianapolis (USA))
Laxmidhar Rout (India): Post-doc, 2013-2014 (afterwards: Assistant Professor, Berhampur University, India)
Vincent Popoff (France): PhD, 2004-2008; then Post-doc, 2012-2013 (afterwards: stable position at Prevor, France)
Gustaf Rydell (Sweden): Post-Doc, 2010-2013 (afterwards: Return position in Sweden)
Ramya Lakshminaryan (India): PhD, 2009-2012 (afterwards: Post-doc with Elizabeth Miller (UK)), position at Eli Lilly and Company (USA)
Lev Stimmer (Germany): Post-Doc, 2011-2012 (afterwards: Position at CEA, France)
Winfried Römer (Germany): Post-Doc, then CR2 CNRS, 2004-2011 (afterwards: Team leader BIOSS, Freiburg, Germany)
Na Li (China): Post-Doc, 2009-2011 (afterwards: Position at Shanghai Synchrotron Radiation Facility)
Getao Shi (China): PhD, 2007-2011 (afterwards: Post-doc with Alexis Gautreau (France))
Yoko Shiba (Japan): Post-Doc, 2005-2009 (afterwards: Associate Professor, Iwate University, Japan)
Bahne Stechmann (Germany): PhD, 2005-2009 (afterwards: Stable position at EU-OPENSCREEN (Germany))
Vikrant Bhor (India): Post-Doc, 2006-2007 (afterwards: Position in India)
Mohamed Amessou (Morocco): Post-doc, 2001-2006 (afterwards: Post-doc with J. Zucman-Rossi)
David Pina (Spain): Post-doc, 2004-2005 (afterwards: Project officer for Marie-Curie actions of EU)
Agnès Saint-Pol (France): Post-Doc, 2001-2004 (afterwards: Teacher at Sup'Biotech school)
Thomas Falguières (France): PhD, 1999-2004 (afterwards: CR1 CNRS (France))
Belén Yélamos (Spain): Post-doc, 2001-2003 (afterwards: Teaching position at Universidad Complutense de Madrid, Spain)
Frédéric Mallard (France): PhD, 1998-2002 (afterwards: Position at CEA (France))
