UMR3666/U1143 – Chemical Biology of Membranes and Therapeutic Delivery

The objective of the Chemical Biology of Membranes and Therapeutic Delivery Unit is to use the power of synthetic chemistry to create innovative tools for the study and manipulation of membrane biological systems. This establishes a competitive basis for discovery at the forefront of biomedical research.

Our chemical biology research program has the potential to simultaneously produce novel insights into fundamental biological mechanisms, deliver new targets, and supply small-molecule modulators of target activity.

Specifically, we are addressing the following major challenges using these interdisciplinary approaches:

  • targeted delivery of compounds to tumors/immunotherapy
  • small molecule lead discovery (chemical genetics)
  • lysosomotropic targeting
  • glycosphingolipid localization and function
  • membrane mechanics
  • Chem-Seq/ Drug-Seq
  • vectorial proteomics
  • mechanotransduction
  • intracellular signaling

The unit is also involved in the Institut Curie chemical Library platform.

 

Selected publications:

Year of publication: 2017


Salinomycin kills cancer stem cells by sequestering iron in lysosomes. 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*. Nature Chem. DOI: 10.1038/NCHEM.2778, Highlighted in chemical & engineering news

Mechanism of Shiga toxin clustering on membranes. Weria Pezeshkian, Haifei Gao, Senthil Arumugam, Ulrike Becken, Patricia Bassereau, Jean-Claude Florent, John Hjort Ipsen, Ludger Johannes*, Julian C Shillcock*. ACS Nano 11, 314-324 (2017)

Chromatin regulates genome targeting with cisplatin. Emmanouil Zacharioudakis, Poonam Agarwal, Alexandra Bartoli, Nathan Abell, Lavaniya Kunalingam, Valérie Bergoglio, Blerta Xhemalce, Kyle M. Miller*, Raphaël Rodriguez*. Angew. Chem. Int. Ed. DOI: 10.1002/anie.201701144R1

Click quantitative mass spectrometry identifies PIWIL3 as a mechanistic target of RNA interference activator enoxacin in cancer cells. Nathan S. Abell, Marvin Mercado, Tatiana Cañeque, Raphaël Rodriguez*, Blerta Xhemalce*. J. Am. Chem. Soc. 139, 1400-1403 (2017)

 

Year of publication: 2016


Glycosylation-Dependent IFN-γR Partitioning in Lipid and Actin Nanodomains Is Critical for JAK Activation. Cédric M Blouin, Yannick Hamon, Pauline Gonnord, Cédric Boularan, Jérémy Kagan, Christine Viaris de Lesegno, Richard Ruez, Sébastien Mailfert, Nicolas Bertaux, Damarys Loew, Christian Wunder, Ludger Johannes, Guillaume Vogt, Francesc-Xabier Contreras, Didier Marguet, Jean-Laurent Casanova, Céline Galès, Hai-Tao He, Christophe Lamaze. Cell  166, 920-934 (2016)

Persistent cell migration and adhesion rely on retrograde transport of β1 integrin. Massiullah Shafaq-Zadah, Carina S. Gomes-Santos, Sabine Bardin, Paolo Maiuri, Mathieu Maurin, Julian Iranzo, Alexis Gautreau, Christophe Lamaze, Patrick Caswell, Bruno Goud, Ludger Johannes Nat. Cell Biol. 18, 54-64 (2016)

Spatiotemporal control of interferon-induced JAK/STAT signalling and gene transcription by the retromer complex. Daniela Chmiest, Nanaocha Sharma, Natacha Zanin, Christine Viaris de Lesegno, Massiullah Shafaq-Zadah, Vonick Sibut, Florent Dingli, Philippe Hupé, Stephan Wilmes, Jacob Piehler, Damarys Loew, Ludger Johannes, Gideon Schreiber, Christophe Lamaze. Nature Comm. 7, 13476 (2016)

 

Year of publication: 2015


Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis. Henri-François Renard, Mijo Simunovic, Joël Lemière, Emmanuel Boucrot, Maria Daniela Garcia-Castillo, Senthil Arumugam, Valérie Chambon, Christophe Lamaze, Christian Wunder, Anne K Kenworthy, Anne A Schmidt, Harvey T McMahon, Cécile Sykes, Patricia Bassereau, Ludger Johannes. Nature 517, 493-496  (2015)

Synthesis of marmycin A and investigation into its cellular activity. Tatiana Cañeque, Filipe Gomes, Trang Thi Mai, Giovanni Maestri, Max Malacria, Raphaël Rodriguez. Nature Chem. 7, 744-751 (2015)

Key publications

Year of publication 2017

Trang Thi Mai, Ahmed Hamaï, Antje Hienzsch, Tatiana Cañeque, Sebastian Müller, Julien Wicinski, Olivier Cabaud, Christine Leroy, Amandine David, Verónica Acevedo, Akihide Ryo, Christophe Genestier, Daniel Birnbaum, Emmanuelle Charafe-Jauffret, Patrice Codogno, Maryam Mehrpour, Raphaël Rodriguez (2017 May 15)

Salinomycin kills cancer stem cells by sequestering iron in lysosomes

Nature Chemistry : DOI : 10.1038/nchem.2778
Emmanouil Zacharioudakis, Poonam Agarwal, Alexandra Bartoli, Nathan Abell, Lavaniya Kunalingam, Valérie Bergoglio, Blerta Xhemalce, Kyle M. Miller, Raphaël Rodriguez (2017 May 5)

Chromatin Regulates Genome Targeting with Cisplatin

Angewandte Chemie : DOI : 10.1002/anie.201701144
Morgan Pellerano, Sergey Tcherniuk, Corine Perals, Thi Nhu Ngoc Van, Elsa Garcin, Florence Mahuteau-Betzer, Marie-Paule Teulade-Fichou, May C Morris (2017 Apr 22)

Targeting Conformational Activation of CDK2 Kinase.

Biotechnology journal : DOI : 10.1002/biot.201600531
Guillaume Kellermann, Florent Dingli, Vanessa Masson, Daniel Dauzonne, Evelyne Ségal-Bendirdjian, Marie-Paule Teulade-Fichou, Damarys Loew, Sophie Bombard (2017 Mar 1)

Exploring the mechanism of inhibition of human telomerase by cysteine-reactive compounds.

FEBS letters : 591 : 863-874 : DOI : 10.1002/1873-3468.12589
Weria Pezeshkian, Haifei Gao, Senthil Arumugam, Ulrike Becken, Patricia Bassereau, Jean-Claude Florent, John Hjort Ipsen, Ludger Johannes, Julian C Shillcock (2017 Jan 24)

Mechanism of Shiga Toxin Clustering on Membranes

ACS Nano : 11 : 314-324 : DOI : DOI: 10.1021/acsnano.6b05706
Nathan S Abell, Marvin Mercado, Tatiana Cañeque, Raphaël Rodriguez, Blerta Xhemalce (2017 Jan 18)

Click Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells.

Journal of the American Chemical Society : 1400-1403 : DOI : 10.1021/jacs.6b11751