Our laboratory has adopted ‘the small molecule approach’ to biology. We study cell biology at the molecular and atomic levels using an integrated approach combining synthetic organic chemistry and molecular biology techniques. We custom design our probes to interrogate cell processes relevant to human diseases. For example, we have established protocols based on click chemistry to fluorescently label small molecules in cells with the view to shed light on their mechanisms of action. This, combined with multi-omics has revealed previously uncharted molecular features in cells that promote the disease-state, while offering opportunities for small molecule intervention. For instance, we have discovered a novel mechanism of metal uptake involving the plasma membrane glycoprotein CD44 and its ligands hyaluronates. We have identified an iron-dependency of the mesenchymal state of cancer cells, which confer a vulnerability of this cell state to ferroptosis. More recently, we have uncovered a previously uncharted role of mitochondrial copper in the regulation of immune cell activation and epithelial-mesenchymal transition of cancer cells. We found that targeting these metals in the disease-state with in-house small molecules confers therapeutic benefits in vivo. Thus, our laboratory exploits universal principles of physical chemistry and knowledge of biology to impact human medicine.

Key publications
  • A druggable copper-signalling pathway that drives inflammation
    Stéphanie Solier, Sebastian Müller, Tatiana Cañeque, Antoine Versini, Arnaud Mansart, Fabien Sindikubwabo, Leeroy Baron, Laila Emam, Pierre Gestraud, G. Dan Pantoș, Vincent Gandon, Christine Gaillet, Ting-Di Wu, Florent Dingli, Damarys Loew, Sylvain Baulande, Sylvère Durand, Valentin Sencio, Cyril Robil, François Trottein, David Péricat, Emmanuelle Näser, Céline Cougoule, Etienne Meunier, Anne-Laure Bègue, Hélène Salmon, Nicolas Manel, Alain Puisieux, Sarah Watson, Mark A. Dawson, Nicolas Servant, Guido Kroemer, Djillali Annane, Raphaël Rodriguez
  • Discovery of a druggable copper-signaling pathway that drives cell plasticity and inflammation
    Stéphanie Solier, Sebastian Müller, Tatiana Cañeque, Antoine Versini, Leeroy Baron, Pierre Gestraud, Nicolas Servant, Laila Emam, Arnaud Mansart, G. Dan Pantoș, Vincent Gandon, Valentin Sencio, Cyril Robil, François Trottein, Anne-Laure Bègue, Hélène Salmon, Sylvère Durand, Ting-Di Wu, Nicolas Manel, Alain Puisieux, Mark A. Dawson, Sarah Watson, Guido Kroemer, Djillali Annane, Raphaël Rodriguez
  • Pharmacologic Reduction of Mitochondrial Iron Triggers a Noncanonical BAX/BAK-Dependent Cell Death
    Cancer Discovery
    Sylvain Garciaz, Andrew A. Guirguis, Sebastian Müller, Fiona C. Brown, Yih-Chih Chan, Ali Motazedian, Caitlin L. Rowe, James A. Kuzich, Kah Lok Chan, Kevin Tran, Lorey Smith, Laura MacPherson, Brian Liddicoat, Enid Y.N. Lam, Tatiana Cañeque, Marian L. Burr, Véronique Litalien, Giovanna Pomilio, Mathilde Poplineau, Estelle Duprez, Sarah-Jane Dawson, Georg Ramm, Andrew G. Cox, Kristin K. Brown, David C.S. Huang, Andrew H. Wei, Kate McArthur, Raphaël Rodriguez, Mark A. Dawson
  • CD44 regulates epigenetic plasticity by mediating iron endocytosis
    Nature Chemistry
    Sebastian Müller, Fabien Sindikubwabo, Tatiana Cañeque, Anne Lafon, Antoine Versini, Bérangère Lombard, Damarys Loew, Ting-Di Wu, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Adeline Durand, Céline Vallot, Sylvain Baulande, Nicolas Servant, Raphaël Rodriguez
  • Salinomycin kills cancer stem cells by sequestering iron in lysosomes
    Nature Chemistry
    Trang Thi Mai, Ahmed Hamaï, Antje Hienzsch, Tatiana Cañeque, Sebastian Müller, Julien Wicinski, Olivier Cabaud, Christine Leroy, Amandine David, Verónica Acevedo, Akihide Ryo, Christophe Ginestier, Daniel Birnbaum, Emmanuelle Charafe-Jauffret, Patrice Codogno, Maryam Mehrpour, Raphaël Rodriguez
  • Click chemistry enables preclinical evaluation of targeted epigenetic therapies
    Dean S. Tyler, Johanna Vappiani, Tatiana Cañeque, Enid Y. N. Lam, Aoife Ward, Omer Gilan, Yih-Chih Chan, Antje Hienzsch, Anna Rutkowska, Thilo Werner, Anne J. Wagner, Dave Lugo, Richard Gregory, Cesar Ramirez Molina, Neil Garton, Christopher R. Wellaway, Susan Jackson, Laura MacPherson, Margarida Figueiredo, Sabine Stolzenburg, Charles C. Bell, Colin House, Sarah-Jane Dawson, Edwin D. Hawkins, Gerard Drewes, Rab K. Prinjha, Raphaël Rodriguez, Paola Grandi, Mark A. Dawson
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